WEBVTT 00:00.000 --> 00:01.000 align:start position:10% line:84.66% size:5% cc 00:01.000 --> 00:02.700 align:start position:10% line:84.66% size:77.5% >> Hi everybody, and welcome to 00:02.700 --> 00:04.300 align:start position:10% line:84.66% size:42.5% Edgewood College. 00:04.300 --> 00:05.966 align:start position:10% line:84.66% size:77.5% My name is Brenda del Moral and 00:05.966 --> 00:07.466 align:start position:10% line:84.66% size:75% I am an assistant professor in 00:07.466 --> 00:09.533 align:start position:10% line:84.66% size:70% biology in the department of 00:09.533 --> 00:11.800 align:start position:10% line:84.66% size:77.5% biological sciences, and in the 00:11.800 --> 00:13.866 align:start position:10% line:84.66% size:70% school of arts and sciences. 00:13.866 --> 00:15.633 align:start position:10% line:84.66% size:72.5% Edgewood College is a liberal 00:15.633 --> 00:16.700 align:start position:10% line:84.66% size:60% arts college in Madison, 00:16.700 --> 00:18.000 align:start position:10% line:84.66% size:25% Wisconsin. 00:18.000 --> 00:19.700 align:start position:10% line:84.66% size:75% This is our first filming here 00:19.700 --> 00:20.900 align:start position:10% line:84.66% size:50% at Edgewood College. 00:20.900 --> 00:22.200 align:start position:10% line:84.66% size:75% Hopefully they'll be many more 00:22.200 --> 00:23.433 align:start position:10% line:84.66% size:20% to come. 00:23.433 --> 00:24.766 align:start position:10% line:84.66% size:80% I'm really excited today to talk 00:24.766 --> 00:26.666 align:start position:10% line:84.66% size:72.5% to you about my talk which is 00:26.666 --> 00:29.100 align:start position:10% line:84.66% size:75% the neuroscience of addiction. 00:29.100 --> 00:30.500 align:start position:10% line:84.66% size:80% I'm going to take this a systems 00:30.500 --> 00:32.566 align:start position:10% line:84.66% size:80% approach, so my hope is to bring 00:32.566 --> 00:34.433 align:start position:10% line:84.66% size:67.5% you through a multi-leveled 00:34.433 --> 00:35.766 align:start position:10% line:84.66% size:65% approach to the disease of 00:35.766 --> 00:37.666 align:start position:10% line:84.66% size:80% addiction and how it effects the 00:37.666 --> 00:40.600 align:start position:10% line:84.66% size:60% whole organism down to a 00:40.600 --> 00:41.900 align:start position:10% line:84.66% size:40% molecular level. 00:41.900 --> 00:43.233 align:start position:10% line:84.66% size:75% And even possibly bring you to 00:43.233 --> 00:45.033 align:start position:10% line:84.66% size:50% the next generation. 00:45.033 --> 00:46.200 align:start position:10% line:84.66% size:70% This is actually our college 00:46.200 --> 00:47.366 align:start position:10% line:84.66% size:27.5% right here. 00:47.366 --> 00:49.133 align:start position:10% line:84.66% size:80% This is the Sonderegger building 00:49.133 --> 00:52.800 align:start position:10% line:84.66% size:77.5% where I spend a lot of my time. 00:52.800 --> 00:56.300 align:start position:10% line:84.66% size:57.5% When scientists, myself 00:56.300 --> 00:57.900 align:start position:10% line:84.66% size:75% included, start thinking about 00:57.900 --> 01:00.233 align:start position:10% line:84.66% size:80% how an addiction is defined as a 01:00.233 --> 01:02.166 align:start position:10% line:84.66% size:70% disease one of the important 01:02.166 --> 01:04.033 align:start position:10% line:84.66% size:57.5% things is to frame what 01:04.033 --> 01:05.333 align:start position:10% line:84.66% size:77.5% addiction is and what addiction 01:05.333 --> 01:06.700 align:start position:10% line:84.66% size:15% isn't. 01:06.700 --> 01:08.066 align:start position:10% line:84.66% size:80% There is still actually a lot of 01:08.066 --> 01:09.466 align:start position:10% line:84.66% size:77.5% inaccurate perception among the 01:09.466 --> 01:11.233 align:start position:10% line:84.66% size:67.5% public about addiction as a 01:11.233 --> 01:13.133 align:start position:10% line:84.66% size:20% disease. 01:13.133 --> 01:15.166 align:start position:10% line:84.66% size:77.5% This is actually a disease that 01:15.166 --> 01:17.666 align:start position:10% line:84.66% size:65% effects about 22.1 million 01:17.666 --> 01:19.000 align:start position:10% line:84.66% size:25% Americans. 01:19.000 --> 01:20.366 align:start position:10% line:84.66% size:72.5% This was an estimate that was 01:20.366 --> 01:22.366 align:start position:10% line:84.66% size:55% recently done in 2011. 01:25.500 --> 01:28.033 align:start position:10% line:84.66% size:80% And when we talk about addiction 01:28.033 --> 01:30.066 align:start position:10% line:84.66% size:55% it's actual diagnosis. 01:30.066 --> 01:31.566 align:start position:10% line:84.66% size:75% It's based on something called 01:31.566 --> 01:33.700 align:start position:10% line:84.66% size:80% the Statistical Manual of Mental 01:33.700 --> 01:35.100 align:start position:10% line:84.66% size:25% Disorders. 01:35.100 --> 01:36.333 align:start position:10% line:84.66% size:80% It's commonly referred to as the 01:36.333 --> 01:38.866 align:start position:10% line:84.66% size:17.5% DSM-IV. 01:38.866 --> 01:40.533 align:start position:10% line:84.66% size:57.5% What this means is that 01:40.533 --> 01:42.666 align:start position:10% line:84.66% size:70% approximately three of these 01:42.666 --> 01:44.266 align:start position:10% line:84.66% size:80% criteria need to be met within a 01:44.266 --> 01:46.666 align:start position:10% line:84.66% size:80% year in order for a person to be 01:46.666 --> 01:48.433 align:start position:10% line:84.66% size:75% diagnosed as a person with the 01:48.433 --> 01:50.166 align:start position:10% line:84.66% size:52.5% disease of addiction. 01:50.166 --> 01:52.200 align:start position:10% line:84.66% size:70% I'm going to use my mouse to 01:52.200 --> 01:53.566 align:start position:10% line:84.66% size:70% point, and hopefully you can 01:53.566 --> 01:55.633 align:start position:10% line:84.66% size:65% follow that on the screen. 01:55.633 --> 01:57.166 align:start position:10% line:84.66% size:50% Here are some of the 01:57.166 --> 01:58.500 align:start position:10% line:84.66% size:70% characteristics that must be 01:58.500 --> 01:59.666 align:start position:10% line:84.66% size:10% met. 01:59.666 --> 02:01.433 align:start position:10% line:84.66% size:75% Tolerance, needing to use more 02:01.433 --> 02:02.933 align:start position:10% line:84.66% size:72.5% of a drug in order to get the 02:02.933 --> 02:04.666 align:start position:10% line:84.66% size:30% same effect. 02:04.666 --> 02:06.666 align:start position:10% line:84.66% size:65% Also, withdrawal symptoms, 02:06.666 --> 02:08.300 align:start position:10% line:84.66% size:70% taking more of the drug on a 02:08.300 --> 02:10.200 align:start position:10% line:84.66% size:35% regular basis. 02:10.200 --> 02:12.500 align:start position:10% line:84.66% size:80% Then also, what is perhaps a bit 02:12.500 --> 02:13.966 align:start position:10% line:84.66% size:67.5% more interesting to me, are 02:13.966 --> 02:16.700 align:start position:10% line:84.66% size:57.5% these lower criteria, a 02:16.700 --> 02:18.666 align:start position:10% line:84.66% size:72.5% persistent desire to use more 02:18.666 --> 02:20.766 align:start position:10% line:84.66% size:62.5% drugs, spending more time 02:20.766 --> 02:22.733 align:start position:10% line:84.66% size:77.5% getting drugs or working to get 02:22.733 --> 02:24.866 align:start position:10% line:84.66% size:77.5% drugs and taking the drugs, and 02:24.866 --> 02:26.900 align:start position:10% line:84.66% size:70% perhaps most interesting, is 02:26.900 --> 02:29.900 align:start position:10% line:84.66% size:72.5% continuing to use these drugs 02:29.900 --> 02:31.066 align:start position:10% line:84.66% size:57.5% despite negative social 02:31.066 --> 02:32.266 align:start position:10% line:84.66% size:32.5% consequences. 02:32.266 --> 02:33.566 align:start position:10% line:84.66% size:80% These can be consequences in the 02:33.566 --> 02:35.366 align:start position:10% line:84.66% size:62.5% work place, among family, 02:35.366 --> 02:36.633 align:start position:10% line:84.66% size:32.5% friends, etc. 02:36.633 --> 02:38.533 align:start position:10% line:84.66% size:55% Or legal consequences. 02:38.533 --> 02:40.800 align:start position:10% line:84.66% size:60% It's this one, this last 02:40.800 --> 02:42.333 align:start position:10% line:84.66% size:72.5% criteria that's most commonly 02:42.333 --> 02:44.400 align:start position:10% line:84.66% size:72.5% used in scientific literature 02:44.400 --> 02:46.466 align:start position:10% line:84.66% size:80% as really being the hallmark for 02:46.466 --> 02:47.700 align:start position:10% line:84.66% size:62.5% the disease of addiction. 02:47.700 --> 02:49.166 align:start position:10% line:84.66% size:57.5% This is one of the most 02:49.166 --> 02:50.400 align:start position:10% line:84.66% size:67.5% important criteria that are 02:50.400 --> 02:53.733 align:start position:10% line:84.66% size:27.5% considered. 02:53.733 --> 02:56.300 align:start position:10% line:84.66% size:65% What really changed public 02:56.300 --> 02:58.366 align:start position:10% line:84.66% size:77.5% perception and was a really big 02:58.366 --> 03:02.233 align:start position:10% line:84.66% size:65% shift, if you will, in how 03:02.233 --> 03:04.366 align:start position:10% line:84.66% size:75% addiction was viewed, was this 03:04.366 --> 03:07.233 align:start position:10% line:84.66% size:80% article that came out in 1997 by 03:07.233 --> 03:08.766 align:start position:10% line:84.66% size:77.5% the former head of the National 03:08.766 --> 03:10.466 align:start position:10% line:84.66% size:60% Institute of Drug Abuse. 03:10.466 --> 03:12.766 align:start position:10% line:84.66% size:62.5% That's often called NIDA. 03:12.766 --> 03:14.733 align:start position:10% line:84.66% size:65% NIDA is one of the funding 03:14.733 --> 03:16.166 align:start position:10% line:84.66% size:72.5% institutes under the National 03:16.166 --> 03:17.666 align:start position:10% line:84.66% size:50% Institute of Health. 03:17.666 --> 03:19.233 align:start position:10% line:84.66% size:70% At the time it came out Alan 03:19.233 --> 03:21.433 align:start position:10% line:84.66% size:70% Leshner said, addiction is a 03:21.433 --> 03:23.666 align:start position:10% line:84.66% size:35% brain disease. 03:23.666 --> 03:25.066 align:start position:10% line:84.66% size:62.5% He wrote about this in an 03:25.066 --> 03:26.900 align:start position:10% line:84.66% size:75% article titled the same thing. 03:26.900 --> 03:28.833 align:start position:10% line:84.66% size:80% That was really a shift from the 03:28.833 --> 03:30.200 align:start position:10% line:84.66% size:75% ideas that had been previously 03:30.200 --> 03:33.900 align:start position:10% line:84.66% size:77.5% been generated about addiction, 03:33.900 --> 03:35.733 align:start position:10% line:84.66% size:62.5% as more of a problem of a 03:35.733 --> 03:37.400 align:start position:10% line:84.66% size:67.5% person's willpower, or just 03:37.400 --> 03:39.233 align:start position:10% line:84.66% size:62.5% simply an inability or an 03:39.233 --> 03:40.933 align:start position:10% line:84.66% size:67.5% unwillingness to stop using 03:40.933 --> 03:42.400 align:start position:10% line:84.66% size:15% drugs. 03:42.400 --> 03:43.800 align:start position:10% line:84.66% size:70% This shifted it more into an 03:43.800 --> 03:45.400 align:start position:10% line:84.66% size:70% actual physiological disease 03:45.400 --> 03:46.800 align:start position:10% line:84.66% size:62.5% much like we would view a 03:46.800 --> 03:48.066 align:start position:10% line:84.66% size:72.5% disease in other parts of the 03:48.066 --> 03:49.600 align:start position:10% line:84.66% size:45% body, for example. 03:49.600 --> 03:51.533 align:start position:10% line:84.66% size:75% He described that in this part 03:51.533 --> 03:53.000 align:start position:10% line:84.66% size:77.5% right here where he talks about 03:53.000 --> 03:55.666 align:start position:10% line:84.66% size:77.5% the good, the bad and the ugly. 03:55.666 --> 03:57.166 align:start position:10% line:84.66% size:70% Part of the criteria that he 03:57.166 --> 03:58.533 align:start position:10% line:84.66% size:60% used to demonstrate that 03:58.533 --> 04:00.366 align:start position:10% line:84.66% size:77.5% addiction is a brain disease is 04:00.366 --> 04:01.900 align:start position:10% line:84.66% size:75% that we know some things about 04:01.900 --> 04:03.866 align:start position:10% line:84.66% size:80% addiction now, and we understand 04:03.866 --> 04:05.833 align:start position:10% line:84.66% size:62.5% some of its physiological 04:05.833 --> 04:07.533 align:start position:10% line:84.66% size:25% processes. 04:07.533 --> 04:09.933 align:start position:10% line:84.66% size:80% For example, the brain circuits, 04:09.933 --> 04:12.200 align:start position:10% line:84.66% size:75% we know the areas of the brain 04:12.200 --> 04:17.700 align:start position:10% line:84.66% size:77.5% that are involved in mediating, 04:17.700 --> 04:19.466 align:start position:10% line:84.66% size:77.5% or in facilitating behaviors of 04:19.466 --> 04:22.000 align:start position:10% line:84.66% size:67.5% drug addiction and physical 04:22.000 --> 04:23.500 align:start position:10% line:84.66% size:27.5% dependence. 04:23.500 --> 04:24.533 align:start position:10% line:84.66% size:70% We know some of the proteins 04:24.533 --> 04:25.933 align:start position:10% line:84.66% size:77.5% that are involved, what we call 04:25.933 --> 04:27.466 align:start position:10% line:84.66% size:25% receptors. 04:27.466 --> 04:28.833 align:start position:10% line:84.66% size:75% We know some of the changes in 04:28.833 --> 04:30.300 align:start position:10% line:84.66% size:62.5% the neurochemistry or the 04:30.300 --> 04:31.466 align:start position:10% line:84.66% size:65% chemicals that change as a 04:31.466 --> 04:33.200 align:start position:10% line:84.66% size:47.5% result of drug use. 04:33.200 --> 04:35.966 align:start position:10% line:84.66% size:80% And we know the overall activity 04:35.966 --> 04:37.633 align:start position:10% line:84.66% size:70% of these areas of the brain. 04:37.633 --> 04:39.233 align:start position:10% line:84.66% size:62.5% So we have some idea that 04:39.233 --> 04:41.600 align:start position:10% line:84.66% size:77.5% addiction really is a change in 04:41.600 --> 04:43.633 align:start position:10% line:84.66% size:80% the physiology and the structure 04:43.633 --> 04:46.533 align:start position:10% line:84.66% size:80% of the brain in certain discrete 04:46.533 --> 04:48.000 align:start position:10% line:84.66% size:15% areas. 04:48.000 --> 04:49.366 align:start position:10% line:84.66% size:77.5% That lends some credence to the 04:49.366 --> 04:51.000 align:start position:10% line:84.66% size:62.5% idea that it's a disease. 04:51.000 --> 04:54.700 align:start position:10% line:84.66% size:70% It's not simply a problem of 04:54.700 --> 04:57.600 align:start position:10% line:84.66% size:60% will power, if you will. 04:57.600 --> 05:00.433 align:start position:10% line:84.66% size:67.5% But there is the down side. 05:00.433 --> 05:02.100 align:start position:10% line:84.66% size:77.5% Part of it, when he talks about 05:02.100 --> 05:04.233 align:start position:10% line:84.66% size:67.5% the bad, is this part right 05:04.233 --> 05:07.000 align:start position:10% line:84.66% size:75% here, public perception of the 05:07.000 --> 05:09.066 align:start position:10% line:84.66% size:52.5% disease of addiction. 05:09.066 --> 05:11.533 align:start position:10% line:84.66% size:65% You know, this was a great 05:11.533 --> 05:13.133 align:start position:10% line:84.66% size:65% shift, if you will, in how 05:13.133 --> 05:16.400 align:start position:10% line:84.66% size:67.5% addiction was though about. 05:16.400 --> 05:18.500 align:start position:10% line:84.66% size:77.5% Also, as science comes out with 05:18.500 --> 05:20.333 align:start position:10% line:84.66% size:77.5% more and more information about 05:20.333 --> 05:23.133 align:start position:10% line:84.66% size:75% what addiction is and what are 05:23.133 --> 05:24.400 align:start position:10% line:84.66% size:62.5% some of the problems, and 05:24.400 --> 05:26.000 align:start position:10% line:84.66% size:80% potentially what are some of the 05:26.000 --> 05:27.333 align:start position:10% line:84.66% size:70% treatments, it's hard to put 05:27.333 --> 05:29.500 align:start position:10% line:84.66% size:77.5% this in practice in the clinic. 05:29.500 --> 05:32.833 align:start position:10% line:84.66% size:75% Translating what occurs in the 05:32.833 --> 05:35.433 align:start position:10% line:84.66% size:75% scientific literature into the 05:35.433 --> 05:36.766 align:start position:10% line:84.66% size:55% clinical and practical 05:36.766 --> 05:39.233 align:start position:10% line:84.66% size:80% application of the literature in 05:39.233 --> 05:40.800 align:start position:10% line:84.66% size:75% treatment facilities or in the 05:40.800 --> 05:42.966 align:start position:10% line:84.66% size:50% clinic is difficult. 05:42.966 --> 05:44.533 align:start position:10% line:84.66% size:67.5% Then there's still some old 05:44.533 --> 05:46.500 align:start position:10% line:84.66% size:65% biases that may persist in 05:46.500 --> 05:47.966 align:start position:10% line:84.66% size:52.5% treatment facilities. 05:47.966 --> 05:49.233 align:start position:10% line:84.66% size:72.5% Oh, I know this worked in the 05:49.233 --> 05:50.600 align:start position:10% line:84.66% size:67.5% past, and it's worked for a 05:50.600 --> 05:52.266 align:start position:10% line:84.66% size:75% great number of people, so I'm 05:52.266 --> 05:53.466 align:start position:10% line:84.66% size:72.5% going to keep doing this even 05:53.466 --> 05:55.133 align:start position:10% line:84.66% size:72.5% though it's been suggested by 05:55.133 --> 05:56.700 align:start position:10% line:84.66% size:52.5% science that it's not 05:56.700 --> 05:58.200 align:start position:10% line:84.66% size:80% particularly helpful, or doesn't 05:58.200 --> 06:00.433 align:start position:10% line:84.66% size:57.5% give any proven result. 06:00.433 --> 06:01.900 align:start position:10% line:84.66% size:72.5% Then there is the really ugly 06:01.900 --> 06:05.166 align:start position:10% line:84.66% size:65% side of addiction which is 06:05.166 --> 06:06.400 align:start position:10% line:84.66% size:47.5% what's listed here. 06:06.400 --> 06:09.133 align:start position:10% line:84.66% size:77.5% Societal stigma continues to be 06:09.133 --> 06:11.800 align:start position:10% line:84.66% size:75% a big problem, especially with 06:11.800 --> 06:13.366 align:start position:10% line:84.66% size:67.5% the aspects of its links to 06:13.366 --> 06:15.733 align:start position:10% line:84.66% size:30% criminality. 06:15.733 --> 06:17.966 align:start position:10% line:84.66% size:72.5% Often times mental illness is 06:17.966 --> 06:19.833 align:start position:10% line:84.66% size:77.5% co-morbid, or it's diagnosed at 06:19.833 --> 06:21.300 align:start position:10% line:84.66% size:67.5% the same time as disease of 06:21.300 --> 06:22.766 align:start position:10% line:84.66% size:25% addiction. 06:22.766 --> 06:24.233 align:start position:10% line:84.66% size:75% So a person might be suffering 06:24.233 --> 06:26.433 align:start position:10% line:84.66% size:77.5% from more than one disease that 06:26.433 --> 06:29.166 align:start position:10% line:84.66% size:67.5% is linked to mental health. 06:29.166 --> 06:31.300 align:start position:10% line:84.66% size:72.5% Also, that these changes that 06:31.300 --> 06:33.000 align:start position:10% line:84.66% size:80% occur from using drugs, and some 06:33.000 --> 06:35.300 align:start position:10% line:84.66% size:75% of which we'll show today, are 06:35.300 --> 06:37.866 align:start position:10% line:84.66% size:77.5% drug changes, changes caused by 06:37.866 --> 06:39.700 align:start position:10% line:84.66% size:65% the drug use, that persist 06:39.700 --> 06:41.866 align:start position:10% line:84.66% size:77.5% throughout the entire time of a 06:41.866 --> 06:44.266 align:start position:10% line:84.66% size:77.5% persons use and even after they 06:44.266 --> 06:46.766 align:start position:10% line:84.66% size:70% have stopped using drugs and 06:46.766 --> 06:48.200 align:start position:10% line:84.66% size:60% they go into a period of 06:48.200 --> 06:49.333 align:start position:10% line:84.66% size:67.5% abstinence where there's no 06:49.333 --> 06:50.633 align:start position:10% line:84.66% size:22.5% drug use. 06:50.633 --> 06:51.766 align:start position:10% line:84.66% size:80% These changes in the brain still 06:51.766 --> 06:53.100 align:start position:10% line:84.66% size:20% persist. 06:53.100 --> 06:54.600 align:start position:10% line:84.66% size:77.5% It's not just that it ends once 06:54.600 --> 06:56.433 align:start position:10% line:84.66% size:45% the drug use ends. 06:56.433 --> 06:57.900 align:start position:10% line:84.66% size:70% These changes that are still 06:57.900 --> 07:00.266 align:start position:10% line:84.66% size:77.5% there continue to persist which 07:00.266 --> 07:02.200 align:start position:10% line:84.66% size:67.5% makes the last point, being 07:02.200 --> 07:04.066 align:start position:10% line:84.66% size:72.5% prone to relapse a particular 07:04.066 --> 07:05.633 align:start position:10% line:84.66% size:20% problem. 07:05.633 --> 07:07.300 align:start position:10% line:84.66% size:77.5% If we think of the circuitry of 07:07.300 --> 07:09.066 align:start position:10% line:84.66% size:65% the brain, the connections 07:09.066 --> 07:10.200 align:start position:10% line:84.66% size:75% between different parts of the 07:10.200 --> 07:12.200 align:start position:10% line:84.66% size:72.5% brain, being hard-wired, then 07:12.200 --> 07:13.766 align:start position:10% line:84.66% size:80% that becomes difficult to change 07:13.766 --> 07:15.600 align:start position:10% line:84.66% size:72.5% within a short period of time 07:15.600 --> 07:16.833 align:start position:10% line:84.66% size:55% that abstinence may be 07:16.833 --> 07:18.300 align:start position:10% line:84.66% size:25% occurring. 07:18.300 --> 07:19.833 align:start position:10% line:84.66% size:65% This was actually a really 07:19.833 --> 07:21.500 align:start position:10% line:84.66% size:77.5% pivotal time for thinking about 07:21.500 --> 07:23.133 align:start position:10% line:84.66% size:62.5% the disease of addiction. 07:23.133 --> 07:25.600 align:start position:10% line:84.66% size:77.5% So when I talk about it, and we 07:25.600 --> 07:27.500 align:start position:10% line:84.66% size:67.5% talk about it in scientific 07:27.500 --> 07:28.966 align:start position:10% line:84.66% size:72.5% literature, what we're really 07:28.966 --> 07:30.666 align:start position:10% line:84.66% size:70% talking about addiction as a 07:30.666 --> 07:32.466 align:start position:10% line:84.66% size:55% chronic brain disease. 07:32.466 --> 07:33.633 align:start position:10% line:84.66% size:52.5% In some cases, even a 07:33.633 --> 07:35.233 align:start position:10% line:84.66% size:72.5% developmental disease, if you 07:35.233 --> 07:36.833 align:start position:10% line:84.66% size:12.5% will. 07:36.833 --> 07:38.566 align:start position:10% line:84.66% size:60% It also has effects that 07:38.566 --> 07:40.866 align:start position:10% line:84.66% size:70% escalate over time, a person 07:40.866 --> 07:42.833 align:start position:10% line:84.66% size:60% continues to use despite 07:42.833 --> 07:45.100 align:start position:10% line:84.66% size:80% negative consequences, sometimes 07:45.100 --> 07:46.800 align:start position:10% line:84.66% size:50% very severe negative 07:46.800 --> 07:49.166 align:start position:10% line:84.66% size:80% consequences, making addiction a 07:49.166 --> 07:53.300 align:start position:10% line:84.66% size:72.5% particularly cunning disease. 07:53.300 --> 07:55.166 align:start position:10% line:84.66% size:60% It's difficult to treat. 07:55.166 --> 07:57.566 align:start position:10% line:84.66% size:77.5% Then also, a person is prone to 07:57.566 --> 07:59.066 align:start position:10% line:84.66% size:20% relapse. 07:59.066 --> 08:01.600 align:start position:10% line:84.66% size:80% If we think about addiction as a 08:01.600 --> 08:03.733 align:start position:10% line:84.66% size:75% disease and in phases of time, 08:03.733 --> 08:06.100 align:start position:10% line:84.66% size:67.5% we can think of it as three 08:06.100 --> 08:08.300 align:start position:10% line:84.66% size:67.5% periods, if we just loosely 08:08.300 --> 08:09.533 align:start position:10% line:84.66% size:32.5% divide it up. 08:09.533 --> 08:10.933 align:start position:10% line:84.66% size:80% There's the initial drug use and 08:10.933 --> 08:12.400 align:start position:10% line:84.66% size:45% drug use exposure. 08:12.400 --> 08:13.966 align:start position:10% line:84.66% size:72.5% This is the initial period of 08:13.966 --> 08:15.766 align:start position:10% line:84.66% size:37.5% drug addiction. 08:15.766 --> 08:16.966 align:start position:10% line:84.66% size:77.5% This is where a person might be 08:16.966 --> 08:18.400 align:start position:10% line:84.66% size:80% experimenting, or just initially 08:18.400 --> 08:20.066 align:start position:10% line:84.66% size:80% using drugs, but has not yet met 08:20.066 --> 08:23.266 align:start position:10% line:84.66% size:80% the three criteria necessary for 08:23.266 --> 08:27.000 align:start position:10% line:84.66% size:80% a diagnosis, but then progresses 08:27.000 --> 08:30.766 align:start position:10% line:84.66% size:72.5% into that phase where you see 08:30.766 --> 08:32.600 align:start position:10% line:84.66% size:72.5% the compulsive behaviors that 08:32.600 --> 08:34.600 align:start position:10% line:84.66% size:77.5% are illicited by drug addiction 08:34.600 --> 08:38.900 align:start position:10% line:84.66% size:70% as well as some of the other 08:38.900 --> 08:40.300 align:start position:10% line:84.66% size:80% criminal behaviors that can also 08:40.300 --> 08:44.433 align:start position:10% line:84.66% size:75% occur that make the getting of 08:44.433 --> 08:46.466 align:start position:10% line:84.66% size:75% the drugs and the using of the 08:46.466 --> 08:48.766 align:start position:10% line:84.66% size:75% drugs foremost on the addict's 08:48.766 --> 08:50.233 align:start position:10% line:84.66% size:12.5% mind. 08:50.233 --> 08:52.000 align:start position:10% line:84.66% size:77.5% Then there can come a period of 08:52.000 --> 08:54.033 align:start position:10% line:84.66% size:80% extinction or abstinence where a 08:54.033 --> 08:55.733 align:start position:10% line:84.66% size:70% person's no longer using the 08:55.733 --> 08:58.233 align:start position:10% line:84.66% size:67.5% drug, and even despite many 08:58.233 --> 09:00.333 align:start position:10% line:84.66% size:67.5% months, sometimes years, of 09:00.333 --> 09:01.900 align:start position:10% line:84.66% size:80% abstinence a person can continue 09:01.900 --> 09:03.200 align:start position:10% line:84.66% size:27.5% to relapse. 09:03.200 --> 09:04.466 align:start position:10% line:84.66% size:67.5% We can think of it in these 09:04.466 --> 09:06.133 align:start position:10% line:84.66% size:32.5% three phases. 09:06.133 --> 09:07.933 align:start position:10% line:84.66% size:77.5% What I'll largely be talking to 09:07.933 --> 09:09.300 align:start position:10% line:84.66% size:70% you about today is this very 09:09.300 --> 09:11.633 align:start position:10% line:84.66% size:75% first one, this initial stage. 09:11.633 --> 09:12.800 align:start position:10% line:84.66% size:70% What really intrigues me and 09:12.800 --> 09:15.433 align:start position:10% line:84.66% size:70% interests me is what happens 09:15.433 --> 09:18.666 align:start position:10% line:84.66% size:80% when a person starts using drugs 09:18.666 --> 09:21.800 align:start position:10% line:84.66% size:62.5% or even starts learning a 09:21.800 --> 09:23.833 align:start position:10% line:84.66% size:80% process that makes it stamped in 09:23.833 --> 09:25.533 align:start position:10% line:84.66% size:57.5% the brain, so to speak. 09:25.533 --> 09:27.100 align:start position:10% line:84.66% size:70% How do we get to that point? 09:27.100 --> 09:28.433 align:start position:10% line:84.66% size:67.5% That's really the part that 09:28.433 --> 09:32.400 align:start position:10% line:84.66% size:55% intrigues me the most. 09:32.400 --> 09:34.266 align:start position:10% line:84.66% size:72.5% When we think about addiction 09:34.266 --> 09:36.933 align:start position:10% line:84.66% size:72.5% we're thinking about it as an 09:36.933 --> 09:38.100 align:start position:10% line:84.66% size:67.5% actual disease and not just 09:38.100 --> 09:41.433 align:start position:10% line:84.66% size:67.5% simply a series of physical 09:41.433 --> 09:42.966 align:start position:10% line:84.66% size:50% withdrawal symptoms. 09:42.966 --> 09:44.466 align:start position:10% line:84.66% size:55% For example, we can be 09:44.466 --> 09:48.833 align:start position:10% line:84.66% size:75% physically tolerant of certain 09:48.833 --> 09:51.033 align:start position:10% line:84.66% size:60% chemicals and experience 09:51.033 --> 09:53.566 align:start position:10% line:84.66% size:75% withdrawal symptoms from them, 09:53.566 --> 09:54.866 align:start position:10% line:84.66% size:70% but that doesn't necessarily 09:54.866 --> 09:57.633 align:start position:10% line:84.66% size:70% mean that they are under the 09:57.633 --> 10:00.166 align:start position:10% line:84.66% size:55% umbrella of addiction. 10:00.166 --> 10:01.400 align:start position:10% line:84.66% size:72.5% For example, I drink a lot of 10:01.400 --> 10:02.700 align:start position:10% line:84.66% size:17.5% coffee. 10:02.700 --> 10:03.866 align:start position:10% line:84.66% size:72.5% I'm well known for drinking a 10:03.866 --> 10:05.066 align:start position:10% line:84.66% size:35% lot of coffee. 10:05.066 --> 10:06.333 align:start position:10% line:84.66% size:80% I feel like I'm always defending 10:06.333 --> 10:07.633 align:start position:10% line:84.66% size:17.5% coffee. 10:07.633 --> 10:10.266 align:start position:10% line:84.66% size:77.5% Coffee does have, in fact-- you 10:10.266 --> 10:11.433 align:start position:10% line:84.66% size:62.5% can build up a tolerance. 10:11.433 --> 10:14.100 align:start position:10% line:84.66% size:80% I know that I myself have a mild 10:14.100 --> 10:17.100 align:start position:10% line:84.66% size:75% physical dependence on coffee. 10:17.100 --> 10:19.000 align:start position:10% line:84.66% size:57.5% But yet, even with it's 10:19.000 --> 10:20.266 align:start position:10% line:84.66% size:60% withdrawal symptoms, the 10:20.266 --> 10:21.466 align:start position:10% line:84.66% size:65% withdrawal symptoms aren't 10:21.466 --> 10:23.366 align:start position:10% line:84.66% size:72.5% sufficient that I will go out 10:23.366 --> 10:25.400 align:start position:10% line:84.66% size:60% and cause a long host of 10:25.400 --> 10:27.100 align:start position:10% line:84.66% size:80% negative consequences for myself 10:27.100 --> 10:28.966 align:start position:10% line:84.66% size:70% in order to get more coffee. 10:28.966 --> 10:32.366 align:start position:10% line:84.66% size:57.5% I will have a headache. 10:32.366 --> 10:33.633 align:start position:10% line:84.66% size:77.5% As an indication of this, I put 10:33.633 --> 10:34.833 align:start position:10% line:84.66% size:70% up a picture of the late Amy 10:34.833 --> 10:36.533 align:start position:10% line:84.66% size:25% Winehouse. 10:36.533 --> 10:38.166 align:start position:10% line:84.66% size:60% Here she is on this side 10:38.166 --> 10:39.733 align:start position:10% line:84.66% size:75% drinking a cup of joe, a good, 10:39.733 --> 10:41.233 align:start position:10% line:84.66% size:70% old fashioned cup of coffee. 10:41.233 --> 10:42.400 align:start position:10% line:84.66% size:45% She looks healthy. 10:42.400 --> 10:43.400 align:start position:10% line:84.66% size:35% She's present. 10:43.400 --> 10:44.600 align:start position:10% line:84.66% size:30% She's alert. 10:44.600 --> 10:45.766 align:start position:10% line:84.66% size:30% She's awake. 10:45.766 --> 10:47.966 align:start position:10% line:84.66% size:72.5% This is Amy Winehouse after a 10:47.966 --> 10:51.566 align:start position:10% line:84.66% size:65% long night of drug use and 10:51.566 --> 10:52.900 align:start position:10% line:84.66% size:57.5% alcohol and drug abuse. 10:52.900 --> 10:54.233 align:start position:10% line:84.66% size:47.5% You can see a clear 10:54.233 --> 10:55.766 align:start position:10% line:84.66% size:30% distinction. 10:55.766 --> 10:57.166 align:start position:10% line:84.66% size:70% When we talk about addiction 10:57.166 --> 10:58.766 align:start position:10% line:84.66% size:75% it's more than just a physical 10:58.766 --> 11:00.966 align:start position:10% line:84.66% size:50% withdrawal symptoms. 11:00.966 --> 11:02.833 align:start position:10% line:84.66% size:70% It's a disease that persists 11:02.833 --> 11:04.366 align:start position:10% line:84.66% size:65% even in the absence of the 11:04.366 --> 11:06.800 align:start position:10% line:84.66% size:15% drugs. 11:06.800 --> 11:11.033 align:start position:10% line:84.66% size:75% When I, and many others, think 11:11.033 --> 11:12.600 align:start position:10% line:84.66% size:77.5% about addiction what I think of 11:12.600 --> 11:15.400 align:start position:10% line:84.66% size:75% addiction as is a disease that 11:15.400 --> 11:17.866 align:start position:10% line:84.66% size:67.5% takes normal learning about 11:17.866 --> 11:19.166 align:start position:10% line:84.66% size:62.5% natural rewards-- natural 11:19.166 --> 11:22.500 align:start position:10% line:84.66% size:77.5% rewards being things like sugar 11:22.500 --> 11:25.166 align:start position:10% line:84.66% size:50% or food, sex, social 11:25.166 --> 11:26.466 align:start position:10% line:84.66% size:72.5% interactions, things that are 11:26.466 --> 11:28.366 align:start position:10% line:84.66% size:62.5% normally reinforcing, and 11:28.366 --> 11:31.100 align:start position:10% line:84.66% size:80% hijacking the brain so that that 11:31.100 --> 11:32.266 align:start position:10% line:84.66% size:65% becomes the most important 11:32.266 --> 11:33.566 align:start position:10% line:84.66% size:15% thing. 11:33.566 --> 11:35.033 align:start position:10% line:84.66% size:80% The pathway in the brain that is 11:35.033 --> 11:37.000 align:start position:10% line:84.66% size:80% solidified or cemented, and that 11:37.000 --> 11:39.333 align:start position:10% line:84.66% size:72.5% keeps getting reinforced over 11:39.333 --> 11:40.800 align:start position:10% line:84.66% size:80% and over at the expense of other 11:40.800 --> 11:42.333 align:start position:10% line:84.66% size:40% natural rewards. 11:42.333 --> 11:43.700 align:start position:10% line:84.66% size:75% And quite frankly, other types 11:43.700 --> 11:46.000 align:start position:10% line:84.66% size:30% of learning. 11:48.400 --> 11:49.766 align:start position:10% line:84.66% size:77.5% I want to take you through what 11:49.766 --> 11:51.533 align:start position:10% line:84.66% size:70% I call a systems approach to 11:51.533 --> 11:52.900 align:start position:10% line:84.66% size:62.5% the disease of addiction. 11:52.900 --> 11:54.433 align:start position:10% line:84.66% size:77.5% For each one of these steps I'm 11:54.433 --> 11:58.333 align:start position:10% line:84.66% size:80% going to give at least one graph 11:58.333 --> 12:00.100 align:start position:10% line:84.66% size:77.5% or set of data that illustrates 12:00.100 --> 12:02.433 align:start position:10% line:84.66% size:75% the point the addiction is not 12:02.433 --> 12:04.100 align:start position:10% line:84.66% size:67.5% just a disease of behavior. 12:04.100 --> 12:05.333 align:start position:10% line:84.66% size:62.5% Although behavior is most 12:05.333 --> 12:07.633 align:start position:10% line:84.66% size:60% prominently what we see, 12:07.633 --> 12:09.566 align:start position:10% line:84.66% size:80% especially as family members, or 12:09.566 --> 12:12.366 align:start position:10% line:84.66% size:60% the public or employers. 12:12.366 --> 12:15.000 align:start position:10% line:84.66% size:67.5% It actually is integrated-- 12:15.000 --> 12:16.100 align:start position:10% line:84.66% size:25% Excuse me. 12:16.100 --> 12:17.300 align:start position:10% line:84.66% size:75% Addiction is a disease that is 12:17.300 --> 12:18.766 align:start position:10% line:84.66% size:65% integrated not just in the 12:18.766 --> 12:21.733 align:start position:10% line:84.66% size:67.5% behavior, but also within a 12:21.733 --> 12:25.033 align:start position:10% line:84.66% size:75% specific pathway in the brain. 12:25.033 --> 12:27.300 align:start position:10% line:84.66% size:67.5% We'll talk about that more. 12:27.300 --> 12:28.866 align:start position:10% line:84.66% size:80% Addiction even goes beyond that. 12:28.866 --> 12:30.333 align:start position:10% line:84.66% size:77.5% It's not just within a specific 12:30.333 --> 12:31.933 align:start position:10% line:84.66% size:75% area, but we can bring it down 12:31.933 --> 12:33.600 align:start position:10% line:84.66% size:80% to the cells within that area of 12:33.600 --> 12:35.300 align:start position:10% line:84.66% size:25% the brain. 12:35.300 --> 12:36.633 align:start position:10% line:84.66% size:77.5% The cells within those areas of 12:36.633 --> 12:37.900 align:start position:10% line:84.66% size:65% the brain we call neurons. 12:37.900 --> 12:40.700 align:start position:10% line:84.66% size:65% Those are the nerve cells. 12:40.700 --> 12:43.633 align:start position:10% line:84.66% size:60% If we stop at the neuron 12:43.633 --> 12:46.000 align:start position:10% line:84.66% size:80% our story is still not complete. 12:46.000 --> 12:47.400 align:start position:10% line:84.66% size:70% There are changes that occur 12:47.400 --> 12:49.733 align:start position:10% line:84.66% size:65% within the neuron that can 12:49.733 --> 12:52.733 align:start position:10% line:84.66% size:75% activate or silence genes that 12:52.733 --> 12:56.500 align:start position:10% line:84.66% size:72.5% will reiterate, or reinforce, 12:56.500 --> 12:58.766 align:start position:10% line:84.66% size:60% this learning process in 12:58.766 --> 13:01.033 align:start position:10% line:84.66% size:25% addiction. 13:01.033 --> 13:02.500 align:start position:10% line:84.66% size:80% I'll even take it a step further 13:02.500 --> 13:04.033 align:start position:10% line:84.66% size:72.5% and say that perhaps it's not 13:04.033 --> 13:05.300 align:start position:10% line:84.66% size:25% just this. 13:05.300 --> 13:06.766 align:start position:10% line:84.66% size:72.5% We might even be able to pass 13:06.766 --> 13:08.166 align:start position:10% line:84.66% size:75% some of these traits on to the 13:08.166 --> 13:10.600 align:start position:10% line:84.66% size:40% next generation. 13:10.600 --> 13:12.400 align:start position:10% line:84.66% size:72.5% That's an equally interesting 13:12.400 --> 13:13.600 align:start position:10% line:84.66% size:65% and potentially terrifying 13:13.600 --> 13:15.633 align:start position:10% line:84.66% size:20% thought. 13:15.633 --> 13:17.566 align:start position:10% line:84.66% size:72.5% Science is starting to really 13:17.566 --> 13:18.933 align:start position:10% line:84.66% size:75% unfold some interesting things 13:18.933 --> 13:20.666 align:start position:10% line:84.66% size:47.5% about this as well. 13:20.666 --> 13:23.300 align:start position:10% line:84.66% size:80% We'll start with, what do I mean 13:23.300 --> 13:25.466 align:start position:10% line:84.66% size:60% by the learning process. 13:25.466 --> 13:26.700 align:start position:10% line:84.66% size:70% There are several schools of 13:26.700 --> 13:28.166 align:start position:10% line:84.66% size:50% thought on learning. 13:28.166 --> 13:29.933 align:start position:10% line:84.66% size:77.5% When I'm talking about the type 13:29.933 --> 13:31.133 align:start position:10% line:84.66% size:80% of learning that I'll be showing 13:31.133 --> 13:32.333 align:start position:10% line:84.66% size:65% you, I'm talking about the 13:32.333 --> 13:34.466 align:start position:10% line:84.66% size:62.5% process of reinforcement. 13:34.466 --> 13:35.900 align:start position:10% line:84.66% size:80% This is where there is some kind 13:35.900 --> 13:37.600 align:start position:10% line:84.66% size:70% of stimulus that is present. 13:37.600 --> 13:38.966 align:start position:10% line:84.66% size:70% In this case here, we have a 13:38.966 --> 13:40.566 align:start position:10% line:84.66% size:27.5% hungry rat. 13:40.566 --> 13:43.033 align:start position:10% line:84.66% size:72.5% Hunger can be a very powerful 13:43.033 --> 13:45.300 align:start position:10% line:84.66% size:52.5% source of motivation. 13:45.300 --> 13:47.033 align:start position:10% line:84.66% size:77.5% What is reinforced for this rat 13:47.033 --> 13:48.633 align:start position:10% line:84.66% size:52.5% is to go out into its 13:48.633 --> 13:50.500 align:start position:10% line:84.66% size:30% environment. 13:50.500 --> 13:52.133 align:start position:10% line:84.66% size:75% He's very hungry so he's going 13:52.133 --> 13:53.400 align:start position:10% line:84.66% size:62.5% to go out and explore the 13:53.400 --> 13:55.233 align:start position:10% line:84.66% size:75% environment in search of food. 13:55.233 --> 13:57.100 align:start position:10% line:84.66% size:77.5% He finds these garbage cans and 13:57.100 --> 13:59.000 align:start position:10% line:84.66% size:70% within the garbage can is an 13:59.000 --> 14:00.800 align:start position:10% line:84.66% size:15% apple. 14:00.800 --> 14:02.300 align:start position:10% line:84.66% size:72.5% Here is a picture of the rats 14:02.300 --> 14:04.333 align:start position:10% line:84.66% size:42.5% eating the apple. 14:04.333 --> 14:05.933 align:start position:10% line:84.66% size:77.5% Going out and searching for the 14:05.933 --> 14:07.500 align:start position:10% line:84.66% size:55% food, that behavior is 14:07.500 --> 14:10.066 align:start position:10% line:84.66% size:77.5% reinforced by the reinforcer of 14:10.066 --> 14:11.800 align:start position:10% line:84.66% size:40% the food itself. 14:11.800 --> 14:13.100 align:start position:10% line:84.66% size:75% We could also, if we wanted to 14:13.100 --> 14:15.200 align:start position:10% line:84.66% size:67.5% think about this as a human 14:15.200 --> 14:17.200 align:start position:10% line:84.66% size:52.5% corelet, if you will. 14:17.200 --> 14:19.133 align:start position:10% line:84.66% size:70% We can think about this as a 14:19.133 --> 14:21.433 align:start position:10% line:84.66% size:77.5% teenager or a young person, who 14:21.433 --> 14:25.900 align:start position:10% line:84.66% size:80% are particularly vulnerable when 14:25.900 --> 14:27.200 align:start position:10% line:84.66% size:65% it comes to the disease of 14:27.200 --> 14:28.433 align:start position:10% line:84.66% size:25% addiction. 14:28.433 --> 14:30.633 align:start position:10% line:84.66% size:75% We can think of a teenager who 14:30.633 --> 14:33.600 align:start position:10% line:84.66% size:65% is stressed or isolated or 14:33.600 --> 14:36.966 align:start position:10% line:84.66% size:67.5% having some kind of what we 14:36.966 --> 14:38.500 align:start position:10% line:84.66% size:60% might term as a negative 14:38.500 --> 14:41.400 align:start position:10% line:84.66% size:67.5% emotional response, feeling 14:41.400 --> 14:42.766 align:start position:10% line:84.66% size:70% really down, who goes out to 14:42.766 --> 14:45.600 align:start position:10% line:84.66% size:72.5% search his or her environment 14:45.600 --> 14:46.900 align:start position:10% line:84.66% size:25% at school. 14:46.900 --> 14:48.200 align:start position:10% line:84.66% size:72.5% Perhaps they're talking about 14:48.200 --> 14:49.600 align:start position:10% line:84.66% size:75% this to somebody else and they 14:49.600 --> 14:51.100 align:start position:10% line:84.66% size:80% say, oh, you know what I do when 14:51.100 --> 14:52.266 align:start position:10% line:84.66% size:45% I don't feel well. 14:52.266 --> 14:53.400 align:start position:10% line:84.66% size:70% It becomes an encounter with 14:53.400 --> 14:55.000 align:start position:10% line:84.66% size:15% drugs. 14:55.000 --> 14:56.500 align:start position:10% line:84.66% size:75% In this case there's a picture 14:56.500 --> 14:57.900 align:start position:10% line:84.66% size:80% showing a student purchasing the 14:57.900 --> 14:59.633 align:start position:10% line:84.66% size:15% drugs. 14:59.633 --> 15:01.300 align:start position:10% line:84.66% size:80% The young person takes the drugs 15:01.300 --> 15:03.966 align:start position:10% line:84.66% size:50% and feels different. 15:03.966 --> 15:06.400 align:start position:10% line:84.66% size:72.5% They feel, sometimes, better. 15:06.400 --> 15:07.733 align:start position:10% line:84.66% size:77.5% They feel distant from whatever 15:07.733 --> 15:09.266 align:start position:10% line:84.66% size:77.5% was causing them anguish in the 15:09.266 --> 15:11.766 align:start position:10% line:84.66% size:70% first place, but in some way 15:11.766 --> 15:13.733 align:start position:10% line:84.66% size:75% that response is reinforced by 15:13.733 --> 15:15.566 align:start position:10% line:84.66% size:60% feeling better about the 15:15.566 --> 15:17.066 align:start position:10% line:84.66% size:60% situation or the initial 15:17.066 --> 15:19.133 align:start position:10% line:84.66% size:22.5% stimulus. 15:19.133 --> 15:21.433 align:start position:10% line:84.66% size:62.5% We approach this learning 15:21.433 --> 15:23.233 align:start position:10% line:84.66% size:70% process-- This is one of the 15:23.233 --> 15:25.833 align:start position:10% line:84.66% size:67.5% learning processes that can 15:25.833 --> 15:28.300 align:start position:10% line:84.66% size:72.5% become hijacked or focused on 15:28.300 --> 15:29.766 align:start position:10% line:84.66% size:77.5% when we think about the disease 15:29.766 --> 15:33.300 align:start position:10% line:84.66% size:32.5% of addiction. 15:33.300 --> 15:36.000 align:start position:10% line:84.66% size:80% In order to talk about this on a 15:36.000 --> 15:38.600 align:start position:10% line:84.66% size:57.5% systems level I need to 15:38.600 --> 15:40.666 align:start position:10% line:84.66% size:67.5% introduce some parts of the 15:40.666 --> 15:42.600 align:start position:10% line:84.66% size:80% cells of the brain, the neurons, 15:42.600 --> 15:43.833 align:start position:10% line:84.66% size:72.5% and how they communicate with 15:43.833 --> 15:44.566 align:start position:10% line:84.66% size:30% one another. 15:44.566 --> 15:45.800 align:start position:10% line:84.66% size:67.5% Because this becomes really 15:45.800 --> 15:47.166 align:start position:10% line:84.66% size:67.5% important for the circuitry 15:47.166 --> 15:48.533 align:start position:10% line:84.66% size:42.5% within the brain. 15:48.533 --> 15:50.433 align:start position:10% line:84.66% size:80% We have a picture over here of a 15:50.433 --> 15:51.700 align:start position:10% line:84.66% size:17.5% neuron. 15:51.700 --> 15:54.800 align:start position:10% line:84.66% size:80% This neuron can be thought of as 15:54.800 --> 15:56.933 align:start position:10% line:84.66% size:72.5% a typical neuron in the brain 15:56.933 --> 15:58.866 align:start position:10% line:84.66% size:80% that sends and receives signals. 15:58.866 --> 16:00.900 align:start position:10% line:84.66% size:80% Neurons are critically important 16:00.900 --> 16:02.166 align:start position:10% line:84.66% size:47.5% because they're the 16:02.166 --> 16:03.300 align:start position:10% line:84.66% size:67.5% communicators of the brain. 16:03.300 --> 16:04.433 align:start position:10% line:84.66% size:70% These are the cells that are 16:04.433 --> 16:05.733 align:start position:10% line:84.66% size:75% communicating across the areas 16:05.733 --> 16:07.833 align:start position:10% line:84.66% size:77.5% of the brain at are involved in 16:07.833 --> 16:09.500 align:start position:10% line:84.66% size:65% any process, but certainly 16:09.500 --> 16:10.733 align:start position:10% line:84.66% size:55% learning and certainly 16:10.733 --> 16:11.933 align:start position:10% line:84.66% size:25% addiction. 16:11.933 --> 16:14.066 align:start position:10% line:84.66% size:80% If we look at the top here, this 16:14.066 --> 16:15.566 align:start position:10% line:84.66% size:80% part right here is the cell body 16:15.566 --> 16:17.200 align:start position:10% line:84.66% size:77.5% and there are these projections 16:17.200 --> 16:18.566 align:start position:10% line:84.66% size:10% out. 16:18.566 --> 16:21.233 align:start position:10% line:84.66% size:72.5% These projects can branch out 16:21.233 --> 16:23.566 align:start position:10% line:84.66% size:65% like a tree, hence they're 16:23.566 --> 16:25.300 align:start position:10% line:84.66% size:42.5% called dendrites. 16:25.300 --> 16:27.533 align:start position:10% line:84.66% size:65% If we think of a neuron as 16:27.533 --> 16:30.066 align:start position:10% line:84.66% size:75% sending and receiving signals, 16:30.066 --> 16:31.933 align:start position:10% line:84.66% size:77.5% this is the end right here that 16:31.933 --> 16:34.533 align:start position:10% line:84.66% size:50% receives the signal. 16:34.533 --> 16:36.666 align:start position:10% line:84.66% size:65% This is the receiving end. 16:36.666 --> 16:38.533 align:start position:10% line:84.66% size:67.5% Then there is the axon that 16:38.533 --> 16:41.366 align:start position:10% line:84.66% size:67.5% projects down like this and 16:41.366 --> 16:43.100 align:start position:10% line:84.66% size:77.5% makes a contact onto some other 16:43.100 --> 16:45.100 align:start position:10% line:84.66% size:17.5% neuron. 16:45.100 --> 16:47.300 align:start position:10% line:84.66% size:67.5% This axon right here is the 16:47.300 --> 16:49.233 align:start position:10% line:84.66% size:67.5% sending part of the neuron. 16:49.233 --> 16:51.133 align:start position:10% line:84.66% size:72.5% This is what is communicating 16:51.133 --> 16:52.466 align:start position:10% line:84.66% size:72.5% the cell that was received in 16:52.466 --> 16:53.866 align:start position:10% line:84.66% size:67.5% the cell body to some other 16:53.866 --> 16:55.466 align:start position:10% line:84.66% size:12.5% cell. 16:55.466 --> 16:58.933 align:start position:10% line:84.66% size:72.5% What is also sometimes really 16:58.933 --> 17:00.433 align:start position:10% line:84.66% size:77.5% easy to think of is to think of 17:00.433 --> 17:02.000 align:start position:10% line:84.66% size:60% the receiving end, these 17:02.000 --> 17:04.666 align:start position:10% line:84.66% size:75% dendrites, as just being these 17:04.666 --> 17:08.033 align:start position:10% line:84.66% size:75% flat, well, flat surface, much 17:08.033 --> 17:10.300 align:start position:10% line:84.66% size:62.5% like is shown right here. 17:10.300 --> 17:12.333 align:start position:10% line:84.66% size:75% But actually if we look, is we 17:12.333 --> 17:14.466 align:start position:10% line:84.66% size:80% use a powerful enough microscope 17:14.466 --> 17:15.833 align:start position:10% line:84.66% size:60% to look at the dendrites 17:15.833 --> 17:18.566 align:start position:10% line:84.66% size:80% themselves we can see a few that 17:18.566 --> 17:19.900 align:start position:10% line:84.66% size:77.5% are much more like this picture 17:19.900 --> 17:21.366 align:start position:10% line:84.66% size:12.5% here. 17:21.366 --> 17:23.633 align:start position:10% line:84.66% size:77.5% This picture shows you branches 17:23.633 --> 17:24.900 align:start position:10% line:84.66% size:42.5% off the dendrite. 17:24.900 --> 17:26.533 align:start position:10% line:84.66% size:70% Then you can see these small 17:26.533 --> 17:28.233 align:start position:10% line:84.66% size:42.5% areas right here. 17:28.233 --> 17:30.000 align:start position:10% line:84.66% size:75% These areas are projection off 17:30.000 --> 17:32.266 align:start position:10% line:84.66% size:70% of the dendrites themselves. 17:32.266 --> 17:34.566 align:start position:10% line:84.66% size:77.5% These projects of the dendrites 17:34.566 --> 17:36.433 align:start position:10% line:84.66% size:45% are called spines. 17:36.433 --> 17:37.766 align:start position:10% line:84.66% size:75% The spines are actually really 17:37.766 --> 17:39.333 align:start position:10% line:84.66% size:67.5% important because these are 17:39.333 --> 17:40.800 align:start position:10% line:84.66% size:60% critical for integrating 17:40.800 --> 17:42.866 align:start position:10% line:84.66% size:77.5% information that others neurons 17:42.866 --> 17:46.800 align:start position:10% line:84.66% size:60% send to that nerve cell. 17:46.800 --> 17:49.000 align:start position:10% line:84.66% size:77.5% These spines can be present all 17:49.000 --> 17:51.200 align:start position:10% line:84.66% size:27.5% throughout. 17:51.200 --> 17:52.400 align:start position:10% line:84.66% size:67.5% What they really do is they 17:52.400 --> 17:53.600 align:start position:10% line:84.66% size:75% increase surface area and they 17:53.600 --> 17:55.400 align:start position:10% line:84.66% size:77.5% increase the likelihood, or the 17:55.400 --> 17:57.766 align:start position:10% line:84.66% size:77.5% opportunity perhaps, of neurons 17:57.766 --> 18:02.333 align:start position:10% line:84.66% size:77.5% communicating with one another. 18:02.333 --> 18:03.666 align:start position:10% line:84.66% size:50% The point of this is 18:03.666 --> 18:04.766 align:start position:10% line:84.66% size:30% integration. 18:04.766 --> 18:06.066 align:start position:10% line:84.66% size:70% It's really easy to think of 18:06.066 --> 18:08.566 align:start position:10% line:84.66% size:67.5% neurons in the brain as one 18:08.566 --> 18:09.733 align:start position:10% line:84.66% size:62.5% neuron communicating with 18:09.733 --> 18:11.433 align:start position:10% line:84.66% size:50% another neuron, that 18:11.433 --> 18:12.666 align:start position:10% line:84.66% size:62.5% communicates with another 18:12.666 --> 18:13.833 align:start position:10% line:84.66% size:17.5% neuron. 18:13.833 --> 18:15.166 align:start position:10% line:84.66% size:72.5% But that's actually not true. 18:15.166 --> 18:16.466 align:start position:10% line:84.66% size:62.5% Really, learning is about 18:16.466 --> 18:18.066 align:start position:10% line:84.66% size:75% modulating all of these inputs 18:18.066 --> 18:20.300 align:start position:10% line:84.66% size:52.5% onto a neuron itself. 18:20.300 --> 18:22.066 align:start position:10% line:84.66% size:72.5% It's not necessarily a one to 18:22.066 --> 18:23.333 align:start position:10% line:84.66% size:25% one ratio. 18:23.333 --> 18:24.700 align:start position:10% line:84.66% size:80% There can be integration, and in 18:24.700 --> 18:26.166 align:start position:10% line:84.66% size:72.5% fact, we find this is exactly 18:26.166 --> 18:27.933 align:start position:10% line:84.66% size:62.5% what happens in learning. 18:27.933 --> 18:29.733 align:start position:10% line:84.66% size:72.5% It will be multiple processes 18:29.733 --> 18:31.633 align:start position:10% line:84.66% size:77.5% from many different neurons all 18:31.633 --> 18:32.900 align:start position:10% line:84.66% size:65% projecting onto one neuron 18:32.900 --> 18:34.500 align:start position:10% line:84.66% size:17.5% itself. 18:34.500 --> 18:35.900 align:start position:10% line:84.66% size:70% It's not a one to one ratio. 18:35.900 --> 18:37.166 align:start position:10% line:84.66% size:55% It can be many neurons 18:37.166 --> 18:40.133 align:start position:10% line:84.66% size:77.5% projecting and making a contact 18:40.133 --> 18:42.400 align:start position:10% line:84.66% size:52.5% onto just one neuron. 18:42.400 --> 18:45.166 align:start position:10% line:84.66% size:72.5% This contact of one neuron to 18:45.166 --> 18:47.666 align:start position:10% line:84.66% size:65% another we call a synapse. 18:47.666 --> 18:50.200 align:start position:10% line:84.66% size:77.5% Those are some of the ways that 18:50.200 --> 18:53.366 align:start position:10% line:84.66% size:55% integration can occur. 18:53.366 --> 18:56.033 align:start position:10% line:84.66% size:80% Integration is really a cellular 18:56.033 --> 18:58.466 align:start position:10% line:84.66% size:75% way to communicate between one 18:58.466 --> 19:00.166 align:start position:10% line:84.66% size:42.5% cell and another. 19:00.166 --> 19:01.666 align:start position:10% line:84.66% size:77.5% In fact, we talk about learning 19:01.666 --> 19:03.033 align:start position:10% line:84.66% size:67.5% as an integration of what's 19:03.033 --> 19:04.900 align:start position:10% line:84.66% size:20% learned. 19:04.900 --> 19:06.100 align:start position:10% line:84.66% size:62.5% It's really honing in and 19:06.100 --> 19:07.366 align:start position:10% line:84.66% size:55% modifying these neural 19:07.366 --> 19:08.800 align:start position:10% line:84.66% size:77.5% connections that becomes really 19:08.800 --> 19:10.266 align:start position:10% line:84.66% size:25% important. 19:10.266 --> 19:11.600 align:start position:10% line:84.66% size:57.5% In fact, in the case of 19:11.600 --> 19:13.033 align:start position:10% line:84.66% size:60% addiction they become so 19:13.033 --> 19:14.566 align:start position:10% line:84.66% size:67.5% hard-wired that things that 19:14.566 --> 19:16.766 align:start position:10% line:84.66% size:62.5% commonly don't seem to be 19:16.766 --> 19:18.166 align:start position:10% line:84.66% size:67.5% affiliated with anything in 19:18.166 --> 19:19.633 align:start position:10% line:84.66% size:75% particular, like a mirror, for 19:19.633 --> 19:21.833 align:start position:10% line:84.66% size:20% example. 19:21.833 --> 19:23.533 align:start position:10% line:84.66% size:72.5% That's just something that we 19:23.533 --> 19:25.233 align:start position:10% line:84.66% size:80% use to get ready in the morning. 19:25.233 --> 19:26.533 align:start position:10% line:84.66% size:60% For somebody that uses a 19:26.533 --> 19:28.233 align:start position:10% line:84.66% size:80% psychostimulant like cocaine, it 19:28.233 --> 19:29.633 align:start position:10% line:84.66% size:75% can have an entirely different 19:29.633 --> 19:31.433 align:start position:10% line:84.66% size:60% meaning, because if it's 19:31.433 --> 19:33.300 align:start position:10% line:84.66% size:77.5% intensive use always correlated 19:33.300 --> 19:35.366 align:start position:10% line:84.66% size:72.5% with the same thing, which is 19:35.366 --> 19:36.533 align:start position:10% line:84.66% size:65% using as it a platform for 19:36.533 --> 19:39.266 align:start position:10% line:84.66% size:30% using drugs. 19:39.266 --> 19:44.033 align:start position:10% line:84.66% size:75% One common misconception about 19:44.033 --> 19:46.466 align:start position:10% line:84.66% size:77.5% learning is about how the brain 19:46.466 --> 19:48.233 align:start position:10% line:84.66% size:55% is actually connected. 19:48.233 --> 19:49.700 align:start position:10% line:84.66% size:67.5% When I'm talking about that 19:49.700 --> 19:51.433 align:start position:10% line:84.66% size:80% connection I'm talking about one 19:51.433 --> 19:53.066 align:start position:10% line:84.66% size:77.5% neuron communicating with other 19:53.066 --> 19:55.200 align:start position:10% line:84.66% size:20% neurons. 19:55.200 --> 19:57.733 align:start position:10% line:84.66% size:75% I think of this often, I think 19:57.733 --> 20:00.100 align:start position:10% line:84.66% size:80% of how students learn and how to 20:00.100 --> 20:01.700 align:start position:10% line:84.66% size:80% best communicate to how students 20:01.700 --> 20:03.066 align:start position:10% line:84.66% size:15% learn. 20:03.066 --> 20:04.566 align:start position:10% line:84.66% size:77.5% We often think of young people, 20:04.566 --> 20:06.500 align:start position:10% line:84.66% size:75% especially, as sponges or open 20:06.500 --> 20:07.866 align:start position:10% line:84.66% size:15% books. 20:07.866 --> 20:09.166 align:start position:10% line:84.66% size:77.5% They're just waiting to suck up 20:09.166 --> 20:11.200 align:start position:10% line:84.66% size:52.5% all this information. 20:11.200 --> 20:12.500 align:start position:10% line:84.66% size:72.5% They don't necessarily have a 20:12.500 --> 20:13.800 align:start position:10% line:84.66% size:52.5% long list of previous 20:13.800 --> 20:16.033 align:start position:10% line:84.66% size:30% experiences. 20:16.033 --> 20:17.766 align:start position:10% line:84.66% size:80% That's true to a certain extent, 20:17.766 --> 20:18.966 align:start position:10% line:84.66% size:62.5% but that's not the entire 20:18.966 --> 20:20.266 align:start position:10% line:84.66% size:20% picture. 20:20.266 --> 20:25.333 align:start position:10% line:84.66% size:65% This is an MRI scan of the 20:25.333 --> 20:26.833 align:start position:10% line:84.66% size:67.5% amount of gray matter, gray 20:26.833 --> 20:28.366 align:start position:10% line:84.66% size:75% matter meaning the areas where 20:28.366 --> 20:30.133 align:start position:10% line:84.66% size:77.5% these neurons are present, in a 20:30.133 --> 20:31.933 align:start position:10% line:84.66% size:50% five year old child. 20:31.933 --> 20:33.933 align:start position:10% line:84.66% size:62.5% That is shown right here. 20:33.933 --> 20:35.600 align:start position:10% line:84.66% size:77.5% Then as that child increases in 20:35.600 --> 20:37.366 align:start position:10% line:84.66% size:10% age. 20:37.366 --> 20:39.400 align:start position:10% line:84.66% size:72.5% If you look at the scale over 20:39.400 --> 20:41.700 align:start position:10% line:84.66% size:75% here you can see that the pink 20:41.700 --> 20:44.166 align:start position:10% line:84.66% size:62.5% and the red areas are the 20:44.166 --> 20:47.000 align:start position:10% line:84.66% size:77.5% greatest amount of gray matter. 20:47.000 --> 20:48.300 align:start position:10% line:84.66% size:77.5% At the bottom are the blues and 20:48.300 --> 20:49.600 align:start position:10% line:84.66% size:30% the purples. 20:49.600 --> 20:51.233 align:start position:10% line:84.66% size:80% You can see that these are areas 20:51.233 --> 20:54.300 align:start position:10% line:84.66% size:70% of a lot of gray matter, the 20:54.300 --> 20:55.966 align:start position:10% line:84.66% size:37.5% highest amount. 20:55.966 --> 21:00.166 align:start position:10% line:84.66% size:72.5% It's not an increase learning 21:00.166 --> 21:01.166 align:start position:10% line:84.66% size:55% over a period of time. 21:01.166 --> 21:02.866 align:start position:10% line:84.66% size:72.5% I think it's safe to say that 21:02.866 --> 21:04.233 align:start position:10% line:84.66% size:77.5% you learn from the ages of five 21:04.233 --> 21:06.166 align:start position:10% line:84.66% size:15% to 20. 21:06.166 --> 21:07.266 align:start position:10% line:84.66% size:75% You're learning things all the 21:07.266 --> 21:08.433 align:start position:10% line:84.66% size:12.5% time. 21:08.433 --> 21:09.700 align:start position:10% line:84.66% size:70% What's not happening is that 21:09.700 --> 21:11.766 align:start position:10% line:84.66% size:77.5% there's an increase necessarily 21:11.766 --> 21:12.900 align:start position:10% line:84.66% size:77.5% in your old connectivity or the 21:12.900 --> 21:14.333 align:start position:10% line:84.66% size:45% amount of neurons. 21:14.333 --> 21:16.100 align:start position:10% line:84.66% size:70% What's actually happening is 21:16.100 --> 21:18.966 align:start position:10% line:84.66% size:67.5% that you are loosing neural 21:18.966 --> 21:20.666 align:start position:10% line:84.66% size:75% connections, and the amount of 21:20.666 --> 21:22.033 align:start position:10% line:84.66% size:77.5% cells that can make connections 21:22.033 --> 21:23.766 align:start position:10% line:84.66% size:62.5% because, as this child is 21:23.766 --> 21:26.300 align:start position:10% line:84.66% size:80% learning, they are honing in and 21:26.300 --> 21:28.533 align:start position:10% line:84.66% size:62.5% focusing the circuits and 21:28.533 --> 21:30.033 align:start position:10% line:84.66% size:65% reinforcing these specific 21:30.033 --> 21:32.066 align:start position:10% line:84.66% size:30% connections. 21:32.066 --> 21:33.433 align:start position:10% line:84.66% size:62.5% The amount of gray matter 21:33.433 --> 21:35.033 align:start position:10% line:84.66% size:72.5% doesn't increase as we learn, 21:35.033 --> 21:37.133 align:start position:10% line:84.66% size:70% and not necessarily does the 21:37.133 --> 21:38.500 align:start position:10% line:84.66% size:65% neural connectivity or the 21:38.500 --> 21:40.833 align:start position:10% line:84.66% size:77.5% number of connections increase, 21:40.833 --> 21:42.266 align:start position:10% line:84.66% size:75% but they become solidified and 21:42.266 --> 21:43.900 align:start position:10% line:84.66% size:27.5% reinforced. 21:43.900 --> 21:46.466 align:start position:10% line:84.66% size:75% They are enhancing our learned 21:46.466 --> 21:49.166 align:start position:10% line:84.66% size:25% knowledge. 21:49.166 --> 21:52.033 align:start position:10% line:84.66% size:80% As you can see, over time, there 21:52.033 --> 21:53.733 align:start position:10% line:84.66% size:70% is a significant decrease in 21:53.733 --> 21:55.700 align:start position:10% line:84.66% size:80% the amount of gray matter at 20. 21:55.700 --> 21:57.066 align:start position:10% line:84.66% size:72.5% Although this area right here 21:57.066 --> 21:58.533 align:start position:10% line:84.66% size:65% I would like to point out. 21:58.533 --> 21:59.900 align:start position:10% line:84.66% size:77.5% At the age of 20, these are the 21:59.900 --> 22:01.366 align:start position:10% line:84.66% size:42.5% frontal cortices. 22:01.366 --> 22:03.100 align:start position:10% line:84.66% size:72.5% Especially we know within the 22:03.100 --> 22:04.733 align:start position:10% line:84.66% size:80% pre-frontal cortex, this area is 22:04.733 --> 22:08.833 align:start position:10% line:84.66% size:37.5% not solidified. 22:08.833 --> 22:10.766 align:start position:10% line:84.66% size:77.5% It's not fully developed by the 22:10.766 --> 22:11.800 align:start position:10% line:84.66% size:25% age of 20. 22:11.800 --> 22:13.433 align:start position:10% line:84.66% size:75% That actually occurs about age 22:13.433 --> 22:15.566 align:start position:10% line:84.66% size:17.5% 20, 25. 22:15.566 --> 22:17.466 align:start position:10% line:84.66% size:80% What this is also showing, right 22:17.466 --> 22:20.000 align:start position:10% line:84.66% size:57.5% here, this is an age of 22:20.000 --> 22:22.266 align:start position:10% line:84.66% size:72.5% incidence for first drug use. 22:22.266 --> 22:25.900 align:start position:10% line:84.66% size:67.5% It shows the extent, or the 22:25.900 --> 22:27.533 align:start position:10% line:84.66% size:77.5% frequency, with which the first 22:27.533 --> 22:29.266 align:start position:10% line:84.66% size:40% drug use occurs. 22:29.266 --> 22:31.333 align:start position:10% line:84.66% size:70% For children or infants it's 22:31.333 --> 22:33.133 align:start position:10% line:84.66% size:27.5% very small. 22:33.133 --> 22:35.566 align:start position:10% line:84.66% size:77.5% Sometimes one or two first drug 22:35.566 --> 22:37.833 align:start position:10% line:84.66% size:72.5% occurrences occur as a child. 22:37.833 --> 22:39.866 align:start position:10% line:84.66% size:72.5% But the most common time when 22:39.866 --> 22:42.133 align:start position:10% line:84.66% size:80% the first drug occurrence occurs 22:42.133 --> 22:43.766 align:start position:10% line:84.66% size:75% within a person's life span is 22:43.766 --> 22:46.133 align:start position:10% line:84.66% size:57.5% when they a teenager or 22:46.133 --> 22:48.033 align:start position:10% line:84.66% size:27.5% adolescent. 22:48.033 --> 22:49.700 align:start position:10% line:84.66% size:80% If we think about the adolescent 22:49.700 --> 22:51.200 align:start position:10% line:84.66% size:50% and teenage years as 22:51.200 --> 22:53.733 align:start position:10% line:84.66% size:57.5% approximately 11 to 19, 22:53.733 --> 22:55.333 align:start position:10% line:84.66% size:70% approximately, and we map it 22:55.333 --> 22:57.566 align:start position:10% line:84.66% size:72.5% over here to this approximate 22:57.566 --> 22:59.200 align:start position:10% line:84.66% size:77.5% time, we're talking about these 22:59.200 --> 23:00.566 align:start position:10% line:84.66% size:65% areas right in here, these 23:00.566 --> 23:01.900 align:start position:10% line:84.66% size:25% timelines. 23:01.900 --> 23:03.233 align:start position:10% line:84.66% size:80% You can see, they're still a lot 23:03.233 --> 23:05.133 align:start position:10% line:84.66% size:80% of development that is occurring 23:05.133 --> 23:07.366 align:start position:10% line:84.66% size:65% and that early exposure to 23:07.366 --> 23:09.566 align:start position:10% line:84.66% size:80% drugs, because there isn't a lot 23:09.566 --> 23:10.766 align:start position:10% line:84.66% size:65% of learning that's already 23:10.766 --> 23:12.733 align:start position:10% line:84.66% size:75% occurred, makes a young person 23:12.733 --> 23:14.466 align:start position:10% line:84.66% size:75% more vulnerable to becoming an 23:14.466 --> 23:16.600 align:start position:10% line:84.66% size:80% addict than perhaps a person who 23:16.600 --> 23:18.366 align:start position:10% line:84.66% size:72.5% is first using drugs later in 23:18.366 --> 23:19.633 align:start position:10% line:84.66% size:12.5% life. 23:19.633 --> 23:20.866 align:start position:10% line:84.66% size:60% We know this to be true. 23:20.866 --> 23:22.100 align:start position:10% line:84.66% size:52.5% There's been a strong 23:22.100 --> 23:24.133 align:start position:10% line:84.66% size:75% correlation established by the 23:24.133 --> 23:26.966 align:start position:10% line:84.66% size:72.5% National Institute of Health. 23:26.966 --> 23:28.800 align:start position:10% line:84.66% size:77.5% So when we talk about the parts 23:28.800 --> 23:30.433 align:start position:10% line:84.66% size:75% of the brain that are involved 23:30.433 --> 23:31.800 align:start position:10% line:84.66% size:70% we're actually talking about 23:31.800 --> 23:34.500 align:start position:10% line:84.66% size:77.5% something that we call commonly 23:34.500 --> 23:36.633 align:start position:10% line:84.66% size:75% the mesolimbic dopamine reward 23:36.633 --> 23:37.833 align:start position:10% line:84.66% size:20% pathway. 23:37.833 --> 23:38.966 align:start position:10% line:84.66% size:72.5% I'm just going to call it the 23:38.966 --> 23:40.200 align:start position:10% line:84.66% size:37.5% reward pathway. 23:40.200 --> 23:42.200 align:start position:10% line:84.66% size:65% That's quite the mouthful. 23:42.200 --> 23:43.566 align:start position:10% line:84.66% size:70% What we're talking about are 23:43.566 --> 23:46.133 align:start position:10% line:84.66% size:77.5% mid-brain areas which release a 23:46.133 --> 23:47.466 align:start position:10% line:84.66% size:72.5% chemical that is often talked 23:47.466 --> 23:49.566 align:start position:10% line:84.66% size:67.5% about in addiction studies. 23:49.566 --> 23:50.666 align:start position:10% line:84.66% size:57.5% That chemical is called 23:50.666 --> 23:52.100 align:start position:10% line:84.66% size:22.5% dopamine. 23:52.100 --> 23:53.700 align:start position:10% line:84.66% size:60% This is a chemical, or a 23:53.700 --> 23:55.533 align:start position:10% line:84.66% size:75% neurotransmitter, that neurons 23:55.533 --> 23:56.733 align:start position:10% line:84.66% size:62.5% use to communicate to one 23:56.733 --> 23:58.200 align:start position:10% line:84.66% size:20% another. 23:58.200 --> 24:01.933 align:start position:10% line:84.66% size:77.5% It's these areas right in here. 24:01.933 --> 24:03.733 align:start position:10% line:84.66% size:75% Then also these striatal areas 24:03.733 --> 24:05.666 align:start position:10% line:84.66% size:65% right here as they project 24:05.666 --> 24:07.233 align:start position:10% line:84.66% size:60% forward to these frontal 24:07.233 --> 24:09.566 align:start position:10% line:84.66% size:37.5% cortices areas. 24:09.566 --> 24:11.666 align:start position:10% line:84.66% size:75% It's these pathways right here 24:11.666 --> 24:13.300 align:start position:10% line:84.66% size:80% that we call, collectively, part 24:13.300 --> 24:15.033 align:start position:10% line:84.66% size:55% of the reward pathway. 24:15.033 --> 24:17.600 align:start position:10% line:84.66% size:75% When I talk about areas of the 24:17.600 --> 24:20.033 align:start position:10% line:84.66% size:65% brain that are involved in 24:20.033 --> 24:23.466 align:start position:10% line:84.66% size:60% learning, addiction, the 24:23.466 --> 24:26.666 align:start position:10% line:84.66% size:72.5% pleasurable feelings of drugs 24:26.666 --> 24:28.433 align:start position:10% line:84.66% size:62.5% that can induce euphoria, 24:28.433 --> 24:30.033 align:start position:10% line:84.66% size:75% motivation, it's these area of 24:30.033 --> 24:31.433 align:start position:10% line:84.66% size:62.5% the brain that I'm really 24:31.433 --> 24:32.733 align:start position:10% line:84.66% size:35% talking about. 24:32.733 --> 24:34.133 align:start position:10% line:84.66% size:75% It's these area that have been 24:34.133 --> 24:35.433 align:start position:10% line:84.66% size:57.5% isolated as part of the 24:35.433 --> 24:37.733 align:start position:10% line:84.66% size:80% important process for developing 24:37.733 --> 24:41.433 align:start position:10% line:84.66% size:62.5% the disease of addiction. 24:41.433 --> 24:44.666 align:start position:10% line:84.66% size:57.5% So if what I showed you 24:44.666 --> 24:46.500 align:start position:10% line:84.66% size:67.5% previously is true that the 24:46.500 --> 24:48.600 align:start position:10% line:84.66% size:80% number of neural connections and 24:48.600 --> 24:50.466 align:start position:10% line:84.66% size:77.5% the number of neurons over time 24:50.466 --> 24:51.866 align:start position:10% line:84.66% size:67.5% may decrease as learning is 24:51.866 --> 24:53.566 align:start position:10% line:84.66% size:65% happening, that a singular 24:53.566 --> 24:55.100 align:start position:10% line:84.66% size:70% pathway or a set of pathways 24:55.100 --> 24:57.466 align:start position:10% line:84.66% size:77.5% becomes reinforced, we actually 24:57.466 --> 25:00.166 align:start position:10% line:84.66% size:77.5% have some data to suggest this. 25:00.166 --> 25:02.666 align:start position:10% line:84.66% size:70% This here is a graph that is 25:02.666 --> 25:04.500 align:start position:10% line:84.66% size:42.5% taken from a rat. 25:04.500 --> 25:07.233 align:start position:10% line:84.66% size:67.5% This set group of rats have 25:07.233 --> 25:08.566 align:start position:10% line:84.66% size:65% exposed to an injection of 25:08.566 --> 25:10.066 align:start position:10% line:84.66% size:77.5% saline which we wouldn't expect 25:10.066 --> 25:12.400 align:start position:10% line:84.66% size:40% any effect from. 25:12.400 --> 25:14.833 align:start position:10% line:84.66% size:72.5% These have been injected with 25:14.833 --> 25:17.033 align:start position:10% line:84.66% size:80% amphetamine, also commonly known 25:17.033 --> 25:18.733 align:start position:10% line:84.66% size:22.5% as speed. 25:18.733 --> 25:21.200 align:start position:10% line:84.66% size:80% These are all of the spines that 25:21.200 --> 25:22.633 align:start position:10% line:84.66% size:62.5% are present on one of the 25:22.633 --> 25:24.866 align:start position:10% line:84.66% size:75% dendrites in a saline injected 25:24.866 --> 25:27.033 align:start position:10% line:84.66% size:57.5% animal, i.e. a control. 25:27.033 --> 25:28.766 align:start position:10% line:84.66% size:70% These are after the drug has 25:28.766 --> 25:30.900 align:start position:10% line:84.66% size:35% been injected. 25:30.900 --> 25:32.433 align:start position:10% line:84.66% size:55% This is just one time. 25:32.433 --> 25:34.133 align:start position:10% line:84.66% size:80% But you can see what's happened. 25:34.133 --> 25:35.666 align:start position:10% line:84.66% size:70% At least I hope you can see, 25:35.666 --> 25:37.266 align:start position:10% line:84.66% size:77.5% that the density, or the number 25:37.266 --> 25:38.933 align:start position:10% line:84.66% size:70% of spines, has significantly 25:38.933 --> 25:40.433 align:start position:10% line:84.66% size:25% increased. 25:40.433 --> 25:41.866 align:start position:10% line:84.66% size:67.5% In fact, if we look at this 25:41.866 --> 25:44.166 align:start position:10% line:84.66% size:75% graphically we can compare the 25:44.166 --> 25:45.733 align:start position:10% line:84.66% size:72.5% saline treated and we can see 25:45.733 --> 25:47.066 align:start position:10% line:84.66% size:65% that there's a much higher 25:47.066 --> 25:48.766 align:start position:10% line:84.66% size:57.5% number of spines in the 25:48.766 --> 25:51.033 align:start position:10% line:84.66% size:50% amphetamine treated. 25:51.033 --> 25:54.533 align:start position:10% line:84.66% size:80% What's actually happening is the 25:54.533 --> 25:56.800 align:start position:10% line:84.66% size:72.5% number of neural connections, 25:56.800 --> 25:58.300 align:start position:10% line:84.66% size:80% connections between neurons, the 25:58.300 --> 25:59.900 align:start position:10% line:84.66% size:80% potential for that is increasing 25:59.900 --> 26:01.300 align:start position:10% line:84.66% size:80% because the number of spines are 26:01.300 --> 26:02.966 align:start position:10% line:84.66% size:27.5% increasing. 26:02.966 --> 26:04.933 align:start position:10% line:84.66% size:75% It's not just necessarily that 26:04.933 --> 26:06.066 align:start position:10% line:84.66% size:60% the number of spines are 26:06.066 --> 26:07.300 align:start position:10% line:84.66% size:27.5% increasing. 26:07.300 --> 26:08.966 align:start position:10% line:84.66% size:75% This picture shows right here, 26:08.966 --> 26:10.433 align:start position:10% line:84.66% size:77.5% this is in the control rat with 26:10.433 --> 26:12.733 align:start position:10% line:84.66% size:60% one spine and some other 26:12.733 --> 26:14.733 align:start position:10% line:84.66% size:47.5% projection onto it. 26:14.733 --> 26:16.066 align:start position:10% line:84.66% size:65% This is in the amphetamine 26:16.066 --> 26:17.400 align:start position:10% line:84.66% size:20% treated. 26:17.400 --> 26:19.066 align:start position:10% line:84.66% size:77.5% There will actually be a growth 26:19.066 --> 26:20.666 align:start position:10% line:84.66% size:80% of the spines in response to the 26:20.666 --> 26:22.433 align:start position:10% line:84.66% size:67.5% drug treatment to reinforce 26:22.433 --> 26:25.600 align:start position:10% line:84.66% size:37.5% those pathways. 26:25.600 --> 26:27.600 align:start position:10% line:84.66% size:72.5% Drugs structurally change the 26:27.600 --> 26:28.833 align:start position:10% line:84.66% size:15% brain. 26:28.833 --> 26:30.166 align:start position:10% line:84.66% size:77.5% And this is just in the initial 26:30.166 --> 26:31.466 align:start position:10% line:84.66% size:25% beginning. 26:31.466 --> 26:33.300 align:start position:10% line:84.66% size:60% With continued drug use, 26:33.300 --> 26:34.966 align:start position:10% line:84.66% size:70% especially of the same type, 26:34.966 --> 26:37.033 align:start position:10% line:84.66% size:77.5% these pathways can have an even 26:37.033 --> 26:39.366 align:start position:10% line:84.66% size:80% greater growth of spines and can 26:39.366 --> 26:42.600 align:start position:10% line:84.66% size:77.5% respond even more strongly, and 26:42.600 --> 26:44.833 align:start position:10% line:84.66% size:62.5% at the exclusion of other 26:44.833 --> 26:46.200 align:start position:10% line:84.66% size:62.5% things, in the disease of 26:46.200 --> 26:49.166 align:start position:10% line:84.66% size:25% addiction. 26:49.166 --> 26:51.333 align:start position:10% line:84.66% size:77.5% If we think of addiction as, in 26:51.333 --> 26:55.533 align:start position:10% line:84.66% size:62.5% some ways, learning being 26:55.533 --> 26:58.233 align:start position:10% line:84.66% size:72.5% hijacked by the brain, we can 26:58.233 --> 26:59.566 align:start position:10% line:84.66% size:75% think of this as a model right 26:59.566 --> 27:00.933 align:start position:10% line:84.66% size:12.5% here. 27:00.933 --> 27:02.266 align:start position:10% line:84.66% size:55% Here is a normal brain 27:02.266 --> 27:03.566 align:start position:10% line:84.66% size:55% undergoing normal life 27:03.566 --> 27:07.433 align:start position:10% line:84.66% size:80% experiences, whatever normal is, 27:07.433 --> 27:09.333 align:start position:10% line:84.66% size:70% but non-drug included set of 27:09.333 --> 27:11.433 align:start position:10% line:84.66% size:30% experiences. 27:11.433 --> 27:13.300 align:start position:10% line:84.66% size:60% It has lots of activity. 27:13.300 --> 27:14.833 align:start position:10% line:84.66% size:52.5% It has lots of neural 27:14.833 --> 27:16.433 align:start position:10% line:84.66% size:32.5% connectivity. 27:16.433 --> 27:17.766 align:start position:10% line:84.66% size:70% This person is able to learn 27:17.766 --> 27:19.200 align:start position:10% line:84.66% size:50% things all the time. 27:19.200 --> 27:20.733 align:start position:10% line:84.66% size:77.5% We can think of this as a model 27:20.733 --> 27:23.000 align:start position:10% line:84.66% size:80% for the addict brain where these 27:23.000 --> 27:24.633 align:start position:10% line:84.66% size:80% reward pathways that are heavily 27:24.633 --> 27:27.333 align:start position:10% line:84.66% size:65% reinforced and it's at the 27:27.333 --> 27:29.133 align:start position:10% line:84.66% size:65% expense of other activity. 27:29.133 --> 27:30.266 align:start position:10% line:84.66% size:75% There's a decrease in activity 27:30.266 --> 27:31.666 align:start position:10% line:84.66% size:80% in other parts of the brain, but 27:31.666 --> 27:33.033 align:start position:10% line:84.66% size:80% the parts that are involved with 27:33.033 --> 27:34.333 align:start position:10% line:84.66% size:62.5% the reward pathway become 27:34.333 --> 27:37.433 align:start position:10% line:84.66% size:35% heavily wired. 27:37.433 --> 27:38.766 align:start position:10% line:84.66% size:70% When we talk about how drugs 27:38.766 --> 27:41.066 align:start position:10% line:84.66% size:77.5% enact their effect in the brain 27:41.066 --> 27:43.633 align:start position:10% line:84.66% size:72.5% what we're talking about is a 27:43.633 --> 27:46.100 align:start position:10% line:84.66% size:72.5% series of chemical changes, a 27:46.100 --> 27:50.400 align:start position:10% line:84.66% size:65% series of protein changes. 27:50.400 --> 27:51.600 align:start position:10% line:84.66% size:77.5% That can occur over a period of 27:51.600 --> 27:52.900 align:start position:10% line:84.66% size:12.5% time. 27:52.900 --> 27:54.733 align:start position:10% line:84.66% size:75% Again, if we take this picture 27:54.733 --> 27:58.200 align:start position:10% line:84.66% size:57.5% right here, this is the 27:58.200 --> 27:59.500 align:start position:10% line:84.66% size:35% receiving end. 27:59.500 --> 28:01.400 align:start position:10% line:84.66% size:80% This is the plasma membrane of a 28:01.400 --> 28:03.333 align:start position:10% line:84.66% size:70% spine of one of the neurons. 28:03.333 --> 28:05.133 align:start position:10% line:84.66% size:75% This is the end that sends the 28:05.133 --> 28:07.500 align:start position:10% line:84.66% size:45% signal right here. 28:07.500 --> 28:10.133 align:start position:10% line:84.66% size:80% This is the very end of the axon 28:10.133 --> 28:11.833 align:start position:10% line:84.66% size:62.5% called the axon terminal. 28:11.833 --> 28:14.033 align:start position:10% line:84.66% size:70% This will release a chemical 28:14.033 --> 28:16.233 align:start position:10% line:84.66% size:70% like a neurotransmitter into 28:16.233 --> 28:17.866 align:start position:10% line:84.66% size:75% this space right here where it 28:17.866 --> 28:19.766 align:start position:10% line:84.66% size:77.5% can then bind to these proteins 28:19.766 --> 28:21.166 align:start position:10% line:84.66% size:77.5% that are embedded in the plasma 28:21.166 --> 28:23.133 align:start position:10% line:84.66% size:65% membrane called receptors. 28:23.133 --> 28:25.566 align:start position:10% line:84.66% size:80% These receptors are specific for 28:25.566 --> 28:27.166 align:start position:10% line:84.66% size:47.5% a certain chemical. 28:27.166 --> 28:28.433 align:start position:10% line:84.66% size:57.5% In this case, these are 28:28.433 --> 28:29.866 align:start position:10% line:84.66% size:67.5% dopamine receptors that are 28:29.866 --> 28:31.833 align:start position:10% line:84.66% size:70% specific to bind only to the 28:31.833 --> 28:33.433 align:start position:10% line:84.66% size:52.5% chemical of dopamine. 28:33.433 --> 28:35.100 align:start position:10% line:84.66% size:40% This is a normal 28:35.100 --> 28:36.466 align:start position:10% line:84.66% size:75% neurotransmission process that 28:36.466 --> 28:38.733 align:start position:10% line:84.66% size:70% occurs in everybody's brain. 28:38.733 --> 28:41.100 align:start position:10% line:84.66% size:72.5% What you can see here is when 28:41.100 --> 28:42.466 align:start position:10% line:84.66% size:62.5% the chemical is released, 28:42.466 --> 28:44.566 align:start position:10% line:84.66% size:70% dopamine, it can be present, 28:44.566 --> 28:45.933 align:start position:10% line:84.66% size:60% these stars, bind to the 28:45.933 --> 28:47.366 align:start position:10% line:84.66% size:75% different protein receptors on 28:47.366 --> 28:49.500 align:start position:10% line:84.66% size:52.5% the receiving neuron. 28:49.500 --> 28:50.800 align:start position:10% line:84.66% size:65% Or it can bind to what are 28:50.800 --> 28:52.733 align:start position:10% line:84.66% size:72.5% called dopamine transporters. 28:52.733 --> 28:54.133 align:start position:10% line:84.66% size:80% These transporters will actually 28:54.133 --> 28:55.633 align:start position:10% line:84.66% size:80% bring the dopamine back into the 28:55.633 --> 28:57.466 align:start position:10% line:84.66% size:77.5% nerve, to the axon terminal, to 28:57.466 --> 28:58.866 align:start position:10% line:84.66% size:27.5% recycle it. 28:58.866 --> 29:00.333 align:start position:10% line:84.66% size:70% It can be used over and over 29:00.333 --> 29:02.666 align:start position:10% line:84.66% size:15% again. 29:02.666 --> 29:04.600 align:start position:10% line:84.66% size:80% What happens with drugs of abuse 29:04.600 --> 29:07.133 align:start position:10% line:84.66% size:75% like cocaine, is that cocaine, 29:07.133 --> 29:09.900 align:start position:10% line:84.66% size:77.5% when a person in exposed, binds 29:09.900 --> 29:11.666 align:start position:10% line:84.66% size:80% to this dopamine transporter and 29:11.666 --> 29:13.266 align:start position:10% line:84.66% size:32.5% it blocks it. 29:13.266 --> 29:14.800 align:start position:10% line:84.66% size:80% This dopamine transporter can no 29:14.800 --> 29:17.400 align:start position:10% line:84.66% size:57.5% longer go back into the 29:17.400 --> 29:19.066 align:start position:10% line:84.66% size:52.5% presynaptic terminal. 29:19.066 --> 29:20.666 align:start position:10% line:84.66% size:77.5% It can no longer go back to the 29:20.666 --> 29:25.000 align:start position:10% line:84.66% size:65% sending end of the neuron. 29:25.000 --> 29:26.733 align:start position:10% line:84.66% size:72.5% What happens then is that all 29:26.733 --> 29:28.566 align:start position:10% line:84.66% size:70% the dopamine is left in that 29:28.566 --> 29:29.866 align:start position:10% line:84.66% size:75% space, and it can keep binding 29:29.866 --> 29:31.300 align:start position:10% line:84.66% size:80% to receptors and keep binding to 29:31.300 --> 29:33.766 align:start position:10% line:84.66% size:77.5% receptors, and continually keep 29:33.766 --> 29:37.600 align:start position:10% line:84.66% size:60% activating these spines. 29:37.600 --> 29:41.966 align:start position:10% line:84.66% size:77.5% So drugs of abuse, like cocaine 29:41.966 --> 29:44.500 align:start position:10% line:84.66% size:77.5% and other psychostimulates, can 29:44.500 --> 29:46.733 align:start position:10% line:84.66% size:67.5% not only effect the protein 29:46.733 --> 29:48.500 align:start position:10% line:84.66% size:70% receptors, but they can also 29:48.500 --> 29:50.533 align:start position:10% line:84.66% size:60% effect the transporters. 29:50.533 --> 29:51.766 align:start position:10% line:84.66% size:72.5% And these effects can be very 29:51.766 --> 29:53.866 align:start position:10% line:84.66% size:32.5% long-lasting. 29:53.866 --> 29:56.833 align:start position:10% line:84.66% size:62.5% As I said before, there's 29:56.833 --> 29:58.566 align:start position:10% line:84.66% size:75% initial changes that happen by 29:58.566 --> 30:01.100 align:start position:10% line:84.66% size:62.5% different drugs of abuse. 30:01.100 --> 30:02.466 align:start position:10% line:84.66% size:60% This is a technique that 30:02.466 --> 30:03.833 align:start position:10% line:84.66% size:77.5% actually, if we go back to this 30:03.833 --> 30:05.066 align:start position:10% line:84.66% size:20% picture. 30:05.066 --> 30:07.533 align:start position:10% line:84.66% size:55% This space right here? 30:07.533 --> 30:09.666 align:start position:10% line:84.66% size:75% A probe can be inserted into a 30:09.666 --> 30:11.266 align:start position:10% line:84.66% size:77.5% specific areas of the brain and 30:11.266 --> 30:13.233 align:start position:10% line:84.66% size:67.5% it can actually measure the 30:13.233 --> 30:14.566 align:start position:10% line:84.66% size:62.5% amount of dopamine that's 30:14.566 --> 30:15.933 align:start position:10% line:84.66% size:75% present in that extra-cellular 30:15.933 --> 30:17.500 align:start position:10% line:84.66% size:77.5% space, the space outside of the 30:17.500 --> 30:18.933 align:start position:10% line:84.66% size:15% cells. 30:18.933 --> 30:20.466 align:start position:10% line:84.66% size:75% That process is called in vivo 30:20.466 --> 30:22.766 align:start position:10% line:84.66% size:35% microdialysis. 30:22.766 --> 30:26.800 align:start position:10% line:84.66% size:80% In this experiment what happened 30:26.800 --> 30:29.100 align:start position:10% line:84.66% size:80% is that animals where exposed to 30:29.100 --> 30:30.866 align:start position:10% line:84.66% size:72.5% different drugs, in this case 30:30.866 --> 30:32.833 align:start position:10% line:84.66% size:75% amphetamine, cocaine, nicotine 30:32.833 --> 30:34.833 align:start position:10% line:84.66% size:32.5% and morphine. 30:34.833 --> 30:36.666 align:start position:10% line:84.66% size:57.5% This process of in vivo 30:36.666 --> 30:38.533 align:start position:10% line:84.66% size:62.5% microdialysis was used to 30:38.533 --> 30:40.166 align:start position:10% line:84.66% size:75% measure the amount of dopamine 30:40.166 --> 30:41.433 align:start position:10% line:84.66% size:75% that's actually present in the 30:41.433 --> 30:43.066 align:start position:10% line:84.66% size:70% extra-cellular space, in the 30:43.066 --> 30:46.633 align:start position:10% line:84.66% size:65% space between two neurons. 30:46.633 --> 30:48.466 align:start position:10% line:84.66% size:70% As you can see here, this is 30:48.466 --> 30:49.733 align:start position:10% line:84.66% size:22.5% dopamine. 30:49.733 --> 30:51.200 align:start position:10% line:84.66% size:75% You can see, after amphetamine 30:51.200 --> 30:53.200 align:start position:10% line:84.66% size:77.5% it rises very sharply, and then 30:53.200 --> 30:54.533 align:start position:10% line:84.66% size:32.5% it decreases. 30:54.533 --> 30:57.600 align:start position:10% line:84.66% size:75% It actually increases ten-fold 30:57.600 --> 30:59.833 align:start position:10% line:84.66% size:72.5% above baseline, above regular 30:59.833 --> 31:03.433 align:start position:10% line:84.66% size:42.5% dopamine release. 31:03.433 --> 31:05.166 align:start position:10% line:84.66% size:67.5% In cocaine you can see that 31:05.166 --> 31:06.700 align:start position:10% line:84.66% size:80% again it elevates and comes back 31:06.700 --> 31:08.133 align:start position:10% line:84.66% size:12.5% down. 31:08.133 --> 31:09.400 align:start position:10% line:84.66% size:67.5% You see this trend also for 31:09.400 --> 31:11.866 align:start position:10% line:84.66% size:77.5% morphine and also for nicotine. 31:11.866 --> 31:13.166 align:start position:10% line:84.66% size:77.5% Nicotine not quite as high, but 31:13.166 --> 31:15.100 align:start position:10% line:84.66% size:35% still present. 31:15.100 --> 31:17.133 align:start position:10% line:84.66% size:77.5% This is with a single injection 31:17.133 --> 31:18.966 align:start position:10% line:84.66% size:60% of the drug, or a single 31:18.966 --> 31:20.466 align:start position:10% line:84.66% size:52.5% exposure to the drug. 31:20.466 --> 31:21.900 align:start position:10% line:84.66% size:80% It greatly elevates the dopamine 31:21.900 --> 31:23.633 align:start position:10% line:84.66% size:67.5% that is present between the 31:23.633 --> 31:25.966 align:start position:10% line:84.66% size:75% cells to keep activating these 31:25.966 --> 31:28.466 align:start position:10% line:84.66% size:70% neurons over and over again. 31:28.466 --> 31:30.433 align:start position:10% line:84.66% size:75% It can be a ten-fold increase. 31:30.433 --> 31:31.900 align:start position:10% line:84.66% size:77.5% It can be a four-fold increase, 31:31.900 --> 31:33.566 align:start position:10% line:84.66% size:60% but it's many times over 31:33.566 --> 31:35.333 align:start position:10% line:84.66% size:52.5% increasing the neuron 31:35.333 --> 31:37.233 align:start position:10% line:84.66% size:80% transmitters that are available, 31:37.233 --> 31:40.700 align:start position:10% line:84.66% size:80% i.e. the activation of the cell. 31:40.700 --> 31:43.433 align:start position:10% line:84.66% size:77.5% Drugs can effect the chemistry. 31:43.433 --> 31:44.800 align:start position:10% line:84.66% size:65% They can also effect these 31:44.800 --> 31:46.433 align:start position:10% line:84.66% size:32.5% transporters. 31:46.433 --> 31:47.666 align:start position:10% line:84.66% size:57.5% This is what's called a 31:47.666 --> 31:49.533 align:start position:10% line:84.66% size:50% functional MRI scan. 31:49.533 --> 31:53.066 align:start position:10% line:84.66% size:80% These are scanned images looking 31:53.066 --> 31:54.800 align:start position:10% line:84.66% size:70% at this dopamine transporter 31:54.800 --> 31:56.866 align:start position:10% line:84.66% size:62.5% which is the protein that 31:56.866 --> 31:58.300 align:start position:10% line:84.66% size:75% carries the dopamine back into 31:58.300 --> 32:00.266 align:start position:10% line:84.66% size:60% the cell to be recycled. 32:00.266 --> 32:02.100 align:start position:10% line:84.66% size:67.5% This is done looking at the 32:02.100 --> 32:04.733 align:start position:10% line:84.66% size:72.5% dopamine transporter activity 32:04.733 --> 32:06.766 align:start position:10% line:84.66% size:75% within this middle area of the 32:06.766 --> 32:08.666 align:start position:10% line:84.66% size:62.5% brain, part of the reward 32:08.666 --> 32:10.100 align:start position:10% line:84.66% size:20% pathway. 32:10.100 --> 32:11.300 align:start position:10% line:84.66% size:67.5% This is in a normal control 32:11.300 --> 32:12.633 align:start position:10% line:84.66% size:17.5% person. 32:12.633 --> 32:14.233 align:start position:10% line:84.66% size:77.5% This is in a person who has not 32:14.233 --> 32:15.966 align:start position:10% line:84.66% size:25% used drug. 32:15.966 --> 32:17.033 align:start position:10% line:84.66% size:70% You can see that it's highly 32:17.033 --> 32:18.233 align:start position:10% line:84.66% size:17.5% active. 32:18.233 --> 32:19.366 align:start position:10% line:84.66% size:77.5% You can compare it to the scale 32:19.366 --> 32:20.566 align:start position:10% line:84.66% size:12.5% here. 32:20.566 --> 32:21.666 align:start position:10% line:84.66% size:75% You can see a very high amount 32:21.666 --> 32:22.766 align:start position:10% line:84.66% size:35% of activation. 32:22.766 --> 32:24.166 align:start position:10% line:84.66% size:80% If we look at a person who was a 32:24.166 --> 32:26.166 align:start position:10% line:84.66% size:80% chronic methamphetamine user who 32:26.166 --> 32:28.166 align:start position:10% line:84.66% size:77.5% has been abstinent and not used 32:28.166 --> 32:29.733 align:start position:10% line:84.66% size:80% the methamphetamine or any other 32:29.733 --> 32:32.800 align:start position:10% line:84.66% size:80% drug for at least one month, you 32:32.800 --> 32:35.466 align:start position:10% line:84.66% size:77.5% can see that despite the period 32:35.466 --> 32:37.100 align:start position:10% line:84.66% size:77.5% of abstinence there's still not 32:37.100 --> 32:38.600 align:start position:10% line:84.66% size:80% as much activity in this area in 32:38.600 --> 32:40.433 align:start position:10% line:84.66% size:72.5% the brain as a normal control 32:40.433 --> 32:41.833 align:start position:10% line:84.66% size:80% person, a person who doesn't use 32:41.833 --> 32:46.000 align:start position:10% line:84.66% size:15% drugs. 32:46.000 --> 32:47.200 align:start position:10% line:84.66% size:57.5% Only after 14 months of 32:47.200 --> 32:49.400 align:start position:10% line:84.66% size:75% abstinence do we only start to 32:49.400 --> 32:51.166 align:start position:10% line:84.66% size:65% see a return to the normal 32:51.166 --> 32:52.700 align:start position:10% line:84.66% size:72.5% amount activity in the brain. 32:52.700 --> 32:54.166 align:start position:10% line:84.66% size:72.5% So 14 months of abstinence is 32:54.166 --> 32:55.800 align:start position:10% line:84.66% size:70% over a year of not using the 32:55.800 --> 32:58.400 align:start position:10% line:84.66% size:80% drugs, and these changes to just 32:58.400 --> 33:00.200 align:start position:10% line:84.66% size:70% this protein alone are still 33:00.200 --> 33:01.466 align:start position:10% line:84.66% size:62.5% present and they're still 33:01.466 --> 33:03.066 align:start position:10% line:84.66% size:27.5% persisting. 33:03.066 --> 33:05.200 align:start position:10% line:84.66% size:75% So despite not having the drug 33:05.200 --> 33:08.166 align:start position:10% line:84.66% size:72.5% in the addict's system, these 33:08.166 --> 33:10.333 align:start position:10% line:84.66% size:72.5% neural changes continue to be 33:10.333 --> 33:12.333 align:start position:10% line:84.66% size:62.5% present within the brain. 33:12.333 --> 33:14.300 align:start position:10% line:84.66% size:77.5% This could potentially set up a 33:14.300 --> 33:15.533 align:start position:10% line:84.66% size:67.5% person to be more likely to 33:15.533 --> 33:17.133 align:start position:10% line:84.66% size:67.5% relapse and start using the 33:17.133 --> 33:20.866 align:start position:10% line:84.66% size:30% drugs again. 33:20.866 --> 33:23.366 align:start position:10% line:84.66% size:52.5% If we look at protein 33:23.366 --> 33:25.033 align:start position:10% line:84.66% size:80% transporters we can also look at 33:25.033 --> 33:26.866 align:start position:10% line:84.66% size:25% receptors. 33:26.866 --> 33:29.000 align:start position:10% line:84.66% size:80% We can model the normal learning 33:29.000 --> 33:31.200 align:start position:10% line:84.66% size:75% that occurs that gets hijacked 33:31.200 --> 33:33.533 align:start position:10% line:84.66% size:70% in the disease of addiction. 33:33.533 --> 33:36.266 align:start position:10% line:84.66% size:72.5% We can use chambers like this 33:36.266 --> 33:38.433 align:start position:10% line:84.66% size:72.5% that is shown with the rat in 33:38.433 --> 33:40.133 align:start position:10% line:84.66% size:27.5% the center. 33:40.133 --> 33:43.633 align:start position:10% line:84.66% size:80% This is called operant learning. 33:43.633 --> 33:46.433 align:start position:10% line:84.66% size:70% This is the type of learning 33:46.433 --> 33:48.100 align:start position:10% line:84.66% size:75% that was discovered and coined 33:48.100 --> 33:50.166 align:start position:10% line:84.66% size:77.5% by B.F. Skinner where you place 33:50.166 --> 33:51.666 align:start position:10% line:84.66% size:75% the rat into what is called an 33:51.666 --> 33:53.233 align:start position:10% line:84.66% size:72.5% operant chamber, or a Skinner 33:53.233 --> 33:54.400 align:start position:10% line:84.66% size:72.5% chamber, depending on who you 33:54.400 --> 33:55.866 align:start position:10% line:84.66% size:20% talk to. 33:55.866 --> 33:58.833 align:start position:10% line:84.66% size:80% You can bring the rat inside and 33:58.833 --> 34:00.766 align:start position:10% line:84.66% size:65% this lever can extend out. 34:00.766 --> 34:03.466 align:start position:10% line:84.66% size:57.5% As you place the rat in 34:03.466 --> 34:04.933 align:start position:10% line:84.66% size:80% initially the rat will go around 34:04.933 --> 34:07.000 align:start position:10% line:84.66% size:70% exploring their environment, 34:07.000 --> 34:08.666 align:start position:10% line:84.66% size:60% which is normal adaptive 34:08.666 --> 34:09.966 align:start position:10% line:84.66% size:22.5% behavior. 34:09.966 --> 34:11.333 align:start position:10% line:84.66% size:80% Maybe it'll accidentally hit, or 34:11.333 --> 34:13.300 align:start position:10% line:84.66% size:72.5% intentionally hit this lever. 34:13.300 --> 34:15.066 align:start position:10% line:84.66% size:75% What can happen is that a food 34:15.066 --> 34:18.000 align:start position:10% line:84.66% size:75% pellet, and in the next case-- 34:18.000 --> 34:20.533 align:start position:10% line:84.66% size:25% excuse me. 34:20.533 --> 34:21.833 align:start position:10% line:84.66% size:70% In the next example that I'm 34:21.833 --> 34:23.066 align:start position:10% line:84.66% size:72.5% going to give, sugar pellets, 34:23.066 --> 34:25.300 align:start position:10% line:84.66% size:60% because rats love sugar. 34:25.300 --> 34:26.866 align:start position:10% line:84.66% size:67.5% This pellet can actually be 34:26.866 --> 34:28.366 align:start position:10% line:84.66% size:72.5% dispensed down into this food 34:28.366 --> 34:29.533 align:start position:10% line:84.66% size:17.5% trough. 34:29.533 --> 34:30.700 align:start position:10% line:84.66% size:77.5% The rat can then go an retrieve 34:30.700 --> 34:32.266 align:start position:10% line:84.66% size:42.5% the sugar pellet. 34:32.266 --> 34:35.266 align:start position:10% line:84.66% size:75% We can automate and record the 34:35.266 --> 34:36.600 align:start position:10% line:84.66% size:75% number of times that the lever 34:36.600 --> 34:38.200 align:start position:10% line:84.66% size:70% is pressed and the number of 34:38.200 --> 34:39.333 align:start position:10% line:84.66% size:72.5% time that the rat goes to get 34:39.333 --> 34:40.433 align:start position:10% line:84.66% size:25% the sugar. 34:40.433 --> 34:41.966 align:start position:10% line:84.66% size:77.5% Quite frankly, rats are willing 34:41.966 --> 34:44.700 align:start position:10% line:84.66% size:77.5% to work for sugar quite a large 34:44.700 --> 34:47.100 align:start position:10% line:84.66% size:70% amount when they are hungry. 34:47.100 --> 34:48.766 align:start position:10% line:84.66% size:80% We're still using the motivation 34:48.766 --> 34:50.066 align:start position:10% line:84.66% size:60% of hunger as the initial 34:50.066 --> 34:51.366 align:start position:10% line:84.66% size:22.5% stimulus. 34:51.366 --> 34:53.800 align:start position:10% line:84.66% size:77.5% This is as example of an albino 34:53.800 --> 34:55.800 align:start position:10% line:84.66% size:75% rat that we use in our studies 34:55.800 --> 34:58.133 align:start position:10% line:84.66% size:25% called --. 34:58.133 --> 34:59.800 align:start position:10% line:84.66% size:67.5% This rat is in the chamber. 34:59.800 --> 35:01.366 align:start position:10% line:84.66% size:70% Here are the levers that can 35:01.366 --> 35:02.466 align:start position:10% line:84.66% size:27.5% extend out. 35:02.466 --> 35:04.066 align:start position:10% line:84.66% size:70% They're not extended at this 35:04.066 --> 35:05.133 align:start position:10% line:84.66% size:15% point. 35:05.133 --> 35:06.233 align:start position:10% line:84.66% size:45% They're retracted. 35:06.233 --> 35:09.233 align:start position:10% line:84.66% size:67.5% But when the session begins 35:09.233 --> 35:12.266 align:start position:10% line:84.66% size:75% these levers will come out and 35:12.266 --> 35:14.233 align:start position:10% line:84.66% size:57.5% the rat can press them. 35:14.233 --> 35:16.166 align:start position:10% line:84.66% size:70% Every press that it gives it 35:16.166 --> 35:18.300 align:start position:10% line:84.66% size:75% receives a sugar pellet in the 35:18.300 --> 35:19.733 align:start position:10% line:84.66% size:17.5% trough. 35:19.733 --> 35:21.000 align:start position:10% line:84.66% size:75% Then he can go enjoy his sugar 35:21.000 --> 35:22.666 align:start position:10% line:84.66% size:72.5% pellet, then press and go and 35:22.666 --> 35:24.300 align:start position:10% line:84.66% size:52.5% enjoy a sugar pellet. 35:24.300 --> 35:27.466 align:start position:10% line:84.66% size:70% And do this many times over. 35:27.466 --> 35:31.133 align:start position:10% line:84.66% size:80% We can use this in multiple ways 35:31.133 --> 35:32.800 align:start position:10% line:84.66% size:80% to study different points in the 35:32.800 --> 35:34.466 align:start position:10% line:84.66% size:50% phases of addiction. 35:34.466 --> 35:36.166 align:start position:10% line:84.66% size:67.5% What I'm most interested in 35:36.166 --> 35:38.200 align:start position:10% line:84.66% size:72.5% learning is what areas of the 35:38.200 --> 35:40.600 align:start position:10% line:84.66% size:72.5% brain, and which proteins the 35:40.600 --> 35:42.933 align:start position:10% line:84.66% size:75% different cells of those areas 35:42.933 --> 35:45.933 align:start position:10% line:84.66% size:65% of the brain guide, or are 35:45.933 --> 35:49.466 align:start position:10% line:84.66% size:75% critical, for the rat learning 35:49.466 --> 35:52.166 align:start position:10% line:84.66% size:77.5% about how pressing the lever is 35:52.166 --> 35:53.800 align:start position:10% line:84.66% size:77.5% reinforced by getting the sugar 35:53.800 --> 35:54.966 align:start position:10% line:84.66% size:17.5% pellet. 35:54.966 --> 35:56.133 align:start position:10% line:84.66% size:65% How it learns this operant 35:56.133 --> 35:57.266 align:start position:10% line:84.66% size:22.5% behavior. 35:57.266 --> 35:58.633 align:start position:10% line:84.66% size:65% Every time it operates the 35:58.633 --> 36:00.366 align:start position:10% line:84.66% size:80% lever, it gets the sugar pellet. 36:00.366 --> 36:02.300 align:start position:10% line:84.66% size:75% How is that learning, or where 36:02.300 --> 36:04.566 align:start position:10% line:84.66% size:72.5% is that learning, held within 36:04.566 --> 36:06.100 align:start position:10% line:84.66% size:25% the brain? 36:06.100 --> 36:07.433 align:start position:10% line:84.66% size:75% We can do studies that look at 36:07.433 --> 36:09.300 align:start position:10% line:84.66% size:12.5% this. 36:09.300 --> 36:10.800 align:start position:10% line:84.66% size:77.5% In this case we can use a rat's 36:10.800 --> 36:12.000 align:start position:10% line:84.66% size:80% willingness to press a lever for 36:12.000 --> 36:13.833 align:start position:10% line:84.66% size:12.5% food. 36:13.833 --> 36:15.166 align:start position:10% line:84.66% size:57.5% We can look at the very 36:15.166 --> 36:16.633 align:start position:10% line:84.66% size:75% beginning, or the acquisition, 36:16.633 --> 36:17.966 align:start position:10% line:84.66% size:42.5% of this behavior. 36:17.966 --> 36:19.366 align:start position:10% line:84.66% size:67.5% We can put the rat into the 36:19.366 --> 36:22.733 align:start position:10% line:84.66% size:72.5% chamber and the rat can start 36:22.733 --> 36:24.400 align:start position:10% line:84.66% size:75% exploring the environment, and 36:24.400 --> 36:26.200 align:start position:10% line:84.66% size:75% start learning that every time 36:26.200 --> 36:27.933 align:start position:10% line:84.66% size:80% he presses the lever he received 36:27.933 --> 36:31.266 align:start position:10% line:84.66% size:77.5% a sugar pellet as a reinforcer. 36:31.266 --> 36:33.400 align:start position:10% line:84.66% size:77.5% In order to find which areas of 36:33.400 --> 36:35.466 align:start position:10% line:84.66% size:70% the brain, and which protein 36:35.466 --> 36:37.900 align:start position:10% line:84.66% size:67.5% receptors are important for 36:37.900 --> 36:39.400 align:start position:10% line:84.66% size:67.5% receiving the signal of the 36:39.400 --> 36:41.133 align:start position:10% line:84.66% size:80% neurotransmitter, what we can do 36:41.133 --> 36:43.533 align:start position:10% line:84.66% size:77.5% is we can use a drug and inject 36:43.533 --> 36:45.900 align:start position:10% line:84.66% size:77.5% it into a very specific part of 36:45.900 --> 36:47.733 align:start position:10% line:84.66% size:72.5% the brain, parts of the brain 36:47.733 --> 36:50.166 align:start position:10% line:84.66% size:80% that are in that reward pathway. 36:50.166 --> 36:52.633 align:start position:10% line:84.66% size:67.5% We can then use a drug that 36:52.633 --> 36:54.733 align:start position:10% line:84.66% size:57.5% blocks these receptors. 36:54.733 --> 36:56.533 align:start position:10% line:84.66% size:72.5% These Xs are representing the 36:56.533 --> 36:59.100 align:start position:10% line:84.66% size:70% blockade of these receptors. 36:59.100 --> 37:01.700 align:start position:10% line:84.66% size:80% If these receptors in a specific 37:01.700 --> 37:03.433 align:start position:10% line:84.66% size:75% part of the brain are involved 37:03.433 --> 37:05.233 align:start position:10% line:84.66% size:80% in mediating this behavior, than 37:05.233 --> 37:08.200 align:start position:10% line:84.66% size:70% rats injected with this drug 37:08.200 --> 37:10.033 align:start position:10% line:84.66% size:80% in the mesolimbic reward pathway 37:10.033 --> 37:11.533 align:start position:10% line:84.66% size:80% will not learn the behavior like 37:11.533 --> 37:14.733 align:start position:10% line:84.66% size:67.5% their control counterparts. 37:14.733 --> 37:16.366 align:start position:10% line:84.66% size:70% As we look at the very first 37:16.366 --> 37:17.700 align:start position:10% line:84.66% size:75% sessions that occur, the first 37:17.700 --> 37:19.100 align:start position:10% line:84.66% size:77.5% five sessions, where the rat is 37:19.100 --> 37:20.700 align:start position:10% line:84.66% size:70% learning about the lever and 37:20.700 --> 37:22.066 align:start position:10% line:84.66% size:75% learning to press the lever in 37:22.066 --> 37:23.766 align:start position:10% line:84.66% size:70% order to receive the pellet. 37:23.766 --> 37:25.466 align:start position:10% line:84.66% size:80% What we can see is these are the 37:25.466 --> 37:28.666 align:start position:10% line:84.66% size:80% saline injected animals with the 37:28.666 --> 37:32.633 align:start position:10% line:84.66% size:52.5% hollow white circles. 37:32.633 --> 37:34.900 align:start position:10% line:84.66% size:72.5% These right here are the drug 37:34.900 --> 37:38.333 align:start position:10% line:84.66% size:42.5% injected animals. 37:38.333 --> 37:40.400 align:start position:10% line:84.66% size:75% These animals have received an 37:40.400 --> 37:42.333 align:start position:10% line:84.66% size:80% injection that blocks a specific 37:42.333 --> 37:44.366 align:start position:10% line:84.66% size:67.5% type of glutamate receptor. 37:44.366 --> 37:45.866 align:start position:10% line:84.66% size:62.5% Glutamate is an important 37:45.866 --> 37:47.400 align:start position:10% line:84.66% size:75% excitatory neurotransmitter in 37:47.400 --> 37:48.600 align:start position:10% line:84.66% size:25% the brain. 37:48.600 --> 37:49.900 align:start position:10% line:84.66% size:72.5% It's actually the most common 37:49.900 --> 37:51.766 align:start position:10% line:84.66% size:10% one. 37:51.766 --> 37:53.700 align:start position:10% line:84.66% size:75% This is in a part of the brain 37:53.700 --> 37:55.700 align:start position:10% line:84.66% size:50% called the straitum. 37:55.700 --> 37:57.100 align:start position:10% line:84.66% size:67.5% This is part of that reward 37:57.100 --> 37:58.500 align:start position:10% line:84.66% size:20% pathway. 37:58.500 --> 38:00.166 align:start position:10% line:84.66% size:77.5% What we find is that the number 38:00.166 --> 38:01.466 align:start position:10% line:84.66% size:65% of lever presses initially 38:01.466 --> 38:02.700 align:start position:10% line:84.66% size:72.5% doesn't have much significant 38:02.700 --> 38:04.100 align:start position:10% line:84.66% size:25% different. 38:04.100 --> 38:05.666 align:start position:10% line:84.66% size:77.5% But as a normal rat, who is not 38:05.666 --> 38:07.866 align:start position:10% line:84.66% size:75% having any drug on-board, this 38:07.866 --> 38:10.566 align:start position:10% line:84.66% size:70% group of rats learned to bar 38:10.566 --> 38:11.833 align:start position:10% line:84.66% size:15% press. 38:11.833 --> 38:13.066 align:start position:10% line:84.66% size:60% Now they're bar pressing 38:13.066 --> 38:14.333 align:start position:10% line:84.66% size:65% approximately 150 times on 38:14.333 --> 38:15.600 align:start position:10% line:84.66% size:77.5% average and getting quite a few 38:15.600 --> 38:17.233 align:start position:10% line:84.66% size:35% sugar pellets. 38:17.233 --> 38:18.433 align:start position:10% line:84.66% size:70% They'll continue to do this. 38:18.433 --> 38:20.200 align:start position:10% line:84.66% size:77.5% We can see that before each one 38:20.200 --> 38:22.800 align:start position:10% line:84.66% size:72.5% of these sessions the animals 38:22.800 --> 38:24.166 align:start position:10% line:84.66% size:77.5% are injected either with saline 38:24.166 --> 38:26.833 align:start position:10% line:84.66% size:42.5% or with the drug. 38:26.833 --> 38:27.866 align:start position:10% line:84.66% size:67.5% These are the rats that are 38:27.866 --> 38:29.266 align:start position:10% line:84.66% size:57.5% injected with the drug. 38:29.266 --> 38:30.533 align:start position:10% line:84.66% size:70% They don't even get up to 50 38:30.533 --> 38:32.133 align:start position:10% line:84.66% size:15% times. 38:32.133 --> 38:33.800 align:start position:10% line:84.66% size:60% Some of them are kind of 38:33.800 --> 38:35.566 align:start position:10% line:84.66% size:80% learning that pressing the level 38:35.566 --> 38:37.433 align:start position:10% line:84.66% size:60% leads to a sugar pellet. 38:37.433 --> 38:40.466 align:start position:10% line:84.66% size:50% Others, not so much. 38:40.466 --> 38:43.466 align:start position:10% line:84.66% size:77.5% In fact, once on this day, this 38:43.466 --> 38:45.500 align:start position:10% line:84.66% size:72.5% dotted line indicates the day 38:45.500 --> 38:47.033 align:start position:10% line:84.66% size:67.5% that the injection stopped. 38:47.033 --> 38:48.533 align:start position:10% line:84.66% size:75% No longer did the rats receive 38:48.533 --> 38:50.100 align:start position:10% line:84.66% size:30% any injects. 38:50.100 --> 38:51.833 align:start position:10% line:84.66% size:75% The control rats are operating 38:51.833 --> 38:53.733 align:start position:10% line:84.66% size:65% at about a standard level. 38:53.733 --> 38:55.466 align:start position:10% line:84.66% size:67.5% Right here, you can see the 38:55.466 --> 38:57.800 align:start position:10% line:84.66% size:80% white dots are all around 200 to 38:57.800 --> 39:00.266 align:start position:10% line:84.66% size:45% 250 lever presses. 39:00.266 --> 39:02.200 align:start position:10% line:84.66% size:72.5% And even after the drug is no 39:02.200 --> 39:04.033 align:start position:10% line:84.66% size:75% longer in their system you can 39:04.033 --> 39:05.833 align:start position:10% line:84.66% size:77.5% see that the rats that had that 39:05.833 --> 39:07.000 align:start position:10% line:84.66% size:60% drug are still trying to 39:07.000 --> 39:08.500 align:start position:10% line:84.66% size:22.5% catch up. 39:08.500 --> 39:09.833 align:start position:10% line:84.66% size:77.5% They eventually do, but it took 39:09.833 --> 39:11.433 align:start position:10% line:84.66% size:72.5% them longer, because they had 39:11.433 --> 39:13.700 align:start position:10% line:84.66% size:80% this receptor in a specific part 39:13.700 --> 39:16.666 align:start position:10% line:84.66% size:52.5% of the brain blocked. 39:16.666 --> 39:18.733 align:start position:10% line:84.66% size:77.5% If we inject them one more time 39:18.733 --> 39:20.033 align:start position:10% line:84.66% size:70% with the drug before putting 39:20.033 --> 39:21.533 align:start position:10% line:84.66% size:77.5% them in the chamber, we can see 39:21.533 --> 39:23.133 align:start position:10% line:84.66% size:35% no difference. 39:23.133 --> 39:24.800 align:start position:10% line:84.66% size:32.5% That matters. 39:24.800 --> 39:26.333 align:start position:10% line:84.66% size:57.5% What that means is that 39:26.333 --> 39:27.966 align:start position:10% line:84.66% size:80% receptor, this type of glutamate 39:27.966 --> 39:29.900 align:start position:10% line:84.66% size:77.5% receptor, in a specific part of 39:29.900 --> 39:32.433 align:start position:10% line:84.66% size:67.5% the straitum, is critically 39:32.433 --> 39:33.833 align:start position:10% line:84.66% size:67.5% important for learning this 39:33.833 --> 39:35.733 align:start position:10% line:84.66% size:72.5% behavior but not carrying out 39:35.733 --> 39:37.100 align:start position:10% line:84.66% size:75% the behavior once it's already 39:37.100 --> 39:38.533 align:start position:10% line:84.66% size:32.5% been learned. 39:38.533 --> 39:39.833 align:start position:10% line:84.66% size:62.5% It's only in that initial 39:39.833 --> 39:41.666 align:start position:10% line:84.66% size:65% acquisition time that this 39:41.666 --> 39:42.966 align:start position:10% line:84.66% size:70% receptor in this part of the 39:42.966 --> 39:45.266 align:start position:10% line:84.66% size:65% brain is really important. 39:45.266 --> 39:46.866 align:start position:10% line:84.66% size:80% This allows up to use a model of 39:46.866 --> 39:49.833 align:start position:10% line:84.66% size:67.5% learning, that is a type of 39:49.833 --> 39:51.966 align:start position:10% line:84.66% size:80% learning that all people do, and 39:51.966 --> 39:53.366 align:start position:10% line:84.66% size:62.5% that gets hijacked in the 39:53.366 --> 39:54.866 align:start position:10% line:84.66% size:62.5% disease of addiction, and 39:54.866 --> 39:56.400 align:start position:10% line:84.66% size:72.5% investigate which proteins in 39:56.400 --> 39:57.600 align:start position:10% line:84.66% size:70% which areas of the brain are 39:57.600 --> 39:59.833 align:start position:10% line:84.66% size:30% responsible. 40:01.466 --> 40:03.066 align:start position:10% line:84.66% size:75% Of course, it would be a short 40:03.066 --> 40:04.600 align:start position:10% line:84.66% size:72.5% story if we ended at just the 40:04.600 --> 40:06.600 align:start position:10% line:84.66% size:25% receptors. 40:06.600 --> 40:07.966 align:start position:10% line:84.66% size:72.5% As I like to always remind my 40:07.966 --> 40:09.133 align:start position:10% line:84.66% size:67.5% students, there are lots of 40:09.133 --> 40:10.433 align:start position:10% line:84.66% size:80% things that happen in the cells, 40:10.433 --> 40:11.666 align:start position:10% line:84.66% size:77.5% besides the receptors, that are 40:11.666 --> 40:14.233 align:start position:10% line:84.66% size:75% present that face the outside. 40:14.233 --> 40:16.300 align:start position:10% line:84.66% size:77.5% This is representing a model of 40:16.300 --> 40:17.966 align:start position:10% line:84.66% size:67.5% a cell which is shown right 40:17.966 --> 40:19.300 align:start position:10% line:84.66% size:12.5% here. 40:19.300 --> 40:20.633 align:start position:10% line:84.66% size:65% This is a receptor that is 40:20.633 --> 40:22.666 align:start position:10% line:84.66% size:77.5% inserted into the membrane, the 40:22.666 --> 40:25.200 align:start position:10% line:84.66% size:25% cell wall. 40:25.200 --> 40:26.933 align:start position:10% line:84.66% size:62.5% When some kind of drug or 40:26.933 --> 40:28.466 align:start position:10% line:84.66% size:65% neurotransmitter binds the 40:28.466 --> 40:30.366 align:start position:10% line:84.66% size:72.5% receptor there are actually a 40:30.366 --> 40:32.766 align:start position:10% line:84.66% size:77.5% whole slough of protein changes 40:32.766 --> 40:34.433 align:start position:10% line:84.66% size:27.5% that occur. 40:34.433 --> 40:36.066 align:start position:10% line:84.66% size:80% It's not like the signal gets to 40:36.066 --> 40:37.300 align:start position:10% line:84.66% size:22.5% the cell. 40:37.300 --> 40:38.700 align:start position:10% line:84.66% size:65% Something has to happen in 40:38.700 --> 40:39.966 align:start position:10% line:84.66% size:77.5% order to change the activity of 40:39.966 --> 40:41.200 align:start position:10% line:84.66% size:22.5% the cell. 40:41.200 --> 40:42.600 align:start position:10% line:84.66% size:72.5% Actually, quite a few protein 40:42.600 --> 40:44.133 align:start position:10% line:84.66% size:65% changes happen in order to 40:44.133 --> 40:46.466 align:start position:10% line:84.66% size:75% change the signal in the cell. 40:46.466 --> 40:50.066 align:start position:10% line:84.66% size:80% These proteins can even get into 40:50.066 --> 40:51.500 align:start position:10% line:84.66% size:60% the nucleus and cause as 40:51.500 --> 40:53.800 align:start position:10% line:84.66% size:80% activation, or an alteration, in 40:53.800 --> 40:57.433 align:start position:10% line:84.66% size:72.5% the transcription of the DNA. 40:57.433 --> 40:59.700 align:start position:10% line:84.66% size:67.5% DNA transcription is really 40:59.700 --> 41:01.533 align:start position:10% line:84.66% size:72.5% important because the process 41:01.533 --> 41:03.066 align:start position:10% line:84.66% size:55% eventually ends in the 41:03.066 --> 41:04.533 align:start position:10% line:84.66% size:47.5% translation, or the 41:04.533 --> 41:05.666 align:start position:10% line:84.66% size:62.5% production, of all of the 41:05.666 --> 41:07.000 align:start position:10% line:84.66% size:22.5% proteins. 41:07.000 --> 41:08.966 align:start position:10% line:84.66% size:80% These proteins are the receptors 41:08.966 --> 41:10.666 align:start position:10% line:84.66% size:52.5% and the transporters. 41:10.666 --> 41:14.766 align:start position:10% line:84.66% size:77.5% The DNA is transcribed and many 41:14.766 --> 41:16.300 align:start position:10% line:84.66% size:75% more of the receptors are made 41:16.300 --> 41:18.133 align:start position:10% line:84.66% size:75% available so that they can now 41:18.133 --> 41:19.800 align:start position:10% line:84.66% size:70% receive the signal coming in 41:19.800 --> 41:21.033 align:start position:10% line:84.66% size:70% because of the repeated drug 41:21.033 --> 41:22.533 align:start position:10% line:84.66% size:10% use. 41:22.533 --> 41:24.100 align:start position:10% line:84.66% size:70% This is a picture right here 41:24.100 --> 41:25.700 align:start position:10% line:84.66% size:72.5% that gives you an idea of the 41:25.700 --> 41:27.100 align:start position:10% line:84.66% size:77.5% number of molecules, this is an 41:27.100 --> 41:29.366 align:start position:10% line:84.66% size:75% abbreviated list of the number 41:29.366 --> 41:31.033 align:start position:10% line:84.66% size:72.5% of protein changes that occur 41:31.033 --> 41:32.900 align:start position:10% line:84.66% size:80% once within the plasma membrane. 41:32.900 --> 41:35.266 align:start position:10% line:84.66% size:67.5% Here are two ascending axon 41:35.266 --> 41:36.600 align:start position:10% line:84.66% size:25% terminals. 41:36.600 --> 41:37.833 align:start position:10% line:84.66% size:77.5% Here's the plasma membrane of a 41:37.833 --> 41:39.100 align:start position:10% line:84.66% size:15% spine. 41:39.100 --> 41:40.466 align:start position:10% line:84.66% size:80% And here are different receptors 41:40.466 --> 41:41.933 align:start position:10% line:84.66% size:80% that are present within the cell 41:41.933 --> 41:43.133 align:start position:10% line:84.66% size:12.5% wall. 41:43.133 --> 41:44.733 align:start position:10% line:84.66% size:62.5% You can see the number of 41:44.733 --> 41:46.033 align:start position:10% line:84.66% size:75% protein changes that can start 41:46.033 --> 41:47.733 align:start position:10% line:84.66% size:77.5% to occur, and how these protein 41:47.733 --> 41:50.266 align:start position:10% line:84.66% size:80% changes can get into the nucleus 41:50.266 --> 41:52.366 align:start position:10% line:84.66% size:75% and actually cause a change in 41:52.366 --> 41:54.566 align:start position:10% line:84.66% size:52.5% transcription of DNA. 41:54.566 --> 41:56.833 align:start position:10% line:84.66% size:72.5% This is how the cell, when it 41:56.833 --> 41:58.600 align:start position:10% line:84.66% size:67.5% receives a signal, actually 41:58.600 --> 42:00.100 align:start position:10% line:84.66% size:70% causes a change in that cell 42:00.100 --> 42:01.700 align:start position:10% line:84.66% size:22.5% activity. 42:01.700 --> 42:05.466 align:start position:10% line:84.66% size:65% It's through this process. 42:05.466 --> 42:07.900 align:start position:10% line:84.66% size:75% We have evidence that learning 42:07.900 --> 42:09.766 align:start position:10% line:84.66% size:70% by itself, and also drugs of 42:09.766 --> 42:11.566 align:start position:10% line:84.66% size:52.5% abuse, can alter gene 42:11.566 --> 42:13.066 align:start position:10% line:84.66% size:30% translation. 42:13.066 --> 42:15.666 align:start position:10% line:84.66% size:67.5% Excuse me, gene expression. 42:15.666 --> 42:17.466 align:start position:10% line:84.66% size:65% This is a technique called 42:17.466 --> 42:19.400 align:start position:10% line:84.66% size:55% in situ hybridization. 42:19.400 --> 42:21.166 align:start position:10% line:84.66% size:72.5% What this does is it looks at 42:21.166 --> 42:23.166 align:start position:10% line:84.66% size:65% gene expression taken from 42:23.166 --> 42:25.166 align:start position:10% line:84.66% size:80% different slices through the rat 42:25.166 --> 42:27.866 align:start position:10% line:84.66% size:50% brain, in this case. 42:27.866 --> 42:29.266 align:start position:10% line:84.66% size:70% The process that I described 42:29.266 --> 42:30.566 align:start position:10% line:84.66% size:72.5% before where the rats are put 42:30.566 --> 42:32.000 align:start position:10% line:84.66% size:77.5% into the chamber and they learn 42:32.000 --> 42:33.633 align:start position:10% line:84.66% size:75% to press the lever in order to 42:33.633 --> 42:35.366 align:start position:10% line:84.66% size:62.5% receive the sugar pellet. 42:35.366 --> 42:36.733 align:start position:10% line:84.66% size:65% This is the same technique 42:36.733 --> 42:38.300 align:start position:10% line:84.66% size:50% that's trained here. 42:38.300 --> 42:40.633 align:start position:10% line:84.66% size:75% In this case these are rats on 42:40.633 --> 42:41.666 align:start position:10% line:84.66% size:57.5% the side, they have had 42:41.666 --> 42:43.600 align:start position:10% line:84.66% size:30% no training. 42:43.600 --> 42:45.100 align:start position:10% line:84.66% size:65% They didn't have the lever 42:45.100 --> 42:46.633 align:start position:10% line:84.66% size:75% extended and they weren't able 42:46.633 --> 42:49.000 align:start position:10% line:84.66% size:65% to learn the same process. 42:49.000 --> 42:52.266 align:start position:10% line:84.66% size:72.5% These are slices showing gene 42:52.266 --> 42:55.400 align:start position:10% line:84.66% size:67.5% expression of a gene called 42:55.400 --> 42:59.766 align:start position:10% line:84.66% size:80% Homer 1A that are in the animals 42:59.766 --> 43:01.800 align:start position:10% line:84.66% size:62.5% that have had the operate 43:01.800 --> 43:02.966 align:start position:10% line:84.66% size:67.5% learning session, that have 43:02.966 --> 43:04.466 align:start position:10% line:84.66% size:75% learned to press the lever for 43:04.466 --> 43:06.533 align:start position:10% line:84.66% size:37.5% the reinforcer. 43:06.533 --> 43:08.000 align:start position:10% line:84.66% size:77.5% These slices are taken from the 43:08.000 --> 43:09.500 align:start position:10% line:84.66% size:80% rats that have just learned this 43:09.500 --> 43:10.666 align:start position:10% line:84.66% size:20% process. 43:10.666 --> 43:12.133 align:start position:10% line:84.66% size:62.5% After the fifth day where 43:12.133 --> 43:13.366 align:start position:10% line:84.66% size:67.5% they're still in that early 43:13.366 --> 43:15.433 align:start position:10% line:84.66% size:77.5% acquisition part, these are the 43:15.433 --> 43:17.366 align:start position:10% line:84.66% size:80% representations from that day of 43:17.366 --> 43:19.400 align:start position:10% line:84.66% size:22.5% learning. 43:19.400 --> 43:20.866 align:start position:10% line:84.66% size:70% You can see, the blue is not 43:20.866 --> 43:22.300 align:start position:10% line:84.66% size:60% indicating a significant 43:22.300 --> 43:24.100 align:start position:10% line:84.66% size:75% activity, but you can see that 43:24.100 --> 43:26.266 align:start position:10% line:84.66% size:80% expression is activated in these 43:26.266 --> 43:28.800 align:start position:10% line:84.66% size:77.5% cortical areas here and are not 43:28.800 --> 43:30.333 align:start position:10% line:84.66% size:70% when you compare them to the 43:30.333 --> 43:32.333 align:start position:10% line:84.66% size:65% animals that didn't learn. 43:32.333 --> 43:34.300 align:start position:10% line:84.66% size:75% So literally, learning changes 43:34.300 --> 43:36.533 align:start position:10% line:84.66% size:65% the expression of what are 43:36.533 --> 43:38.033 align:start position:10% line:84.66% size:72.5% called immediate early genes, 43:38.033 --> 43:41.366 align:start position:10% line:84.66% size:80% the first genes to respond, like 43:41.366 --> 43:42.900 align:start position:10% line:84.66% size:22.5% Homer 1A. 43:42.900 --> 43:44.000 align:start position:10% line:84.66% size:70% It was named after the poet, 43:44.000 --> 43:47.633 align:start position:10% line:84.66% size:65% not the cartoon character. 43:47.633 --> 43:49.066 align:start position:10% line:84.66% size:70% If we look at the expression 43:49.066 --> 43:50.433 align:start position:10% line:84.66% size:75% within these early learners we 43:50.433 --> 43:51.800 align:start position:10% line:84.66% size:70% can see a lot of activity in 43:51.800 --> 43:53.533 align:start position:10% line:84.66% size:75% this area right in here, and a 43:53.533 --> 43:55.200 align:start position:10% line:84.66% size:77.5% lot of activity in this area as 43:55.200 --> 43:56.566 align:start position:10% line:84.66% size:12.5% well. 43:56.566 --> 43:58.066 align:start position:10% line:84.66% size:72.5% If we compare them to animals 43:58.066 --> 43:59.433 align:start position:10% line:84.66% size:72.5% who have already learned this 43:59.433 --> 44:00.966 align:start position:10% line:84.66% size:70% process many times over, the 44:00.966 --> 44:02.400 align:start position:10% line:84.66% size:62.5% activity looks different. 44:02.400 --> 44:03.800 align:start position:10% line:84.66% size:80% We don't see as much within this 44:03.800 --> 44:05.200 align:start position:10% line:84.66% size:75% area, but we see a significant 44:05.200 --> 44:08.000 align:start position:10% line:84.66% size:55% increase in this area. 44:08.000 --> 44:10.133 align:start position:10% line:84.66% size:65% What this shows us is that 44:10.133 --> 44:12.133 align:start position:10% line:84.66% size:75% normal learning can alter gene 44:12.133 --> 44:15.166 align:start position:10% line:84.66% size:27.5% expression. 44:15.166 --> 44:17.766 align:start position:10% line:84.66% size:75% These changes are getting into 44:17.766 --> 44:19.333 align:start position:10% line:84.66% size:80% the nucleus and they are causing 44:19.333 --> 44:22.866 align:start position:10% line:84.66% size:77.5% an activation of transcription. 44:22.866 --> 44:24.233 align:start position:10% line:84.66% size:57.5% And they are leading to 44:24.233 --> 44:25.600 align:start position:10% line:84.66% size:80% different types of proteins that 44:25.600 --> 44:26.700 align:start position:10% line:84.66% size:37.5% are being made. 44:26.700 --> 44:28.266 align:start position:10% line:84.66% size:77.5% This occurs in normal learning, 44:28.266 --> 44:29.833 align:start position:10% line:84.66% size:75% and when this learning process 44:29.833 --> 44:31.066 align:start position:10% line:84.66% size:67.5% gets hijacked, this process 44:31.066 --> 44:33.533 align:start position:10% line:84.66% size:77.5% is even more heavily reinforced 44:33.533 --> 44:37.100 align:start position:10% line:84.66% size:70% in the disease of addiction. 44:37.100 --> 44:40.900 align:start position:10% line:84.66% size:70% What is probably three parts 44:40.900 --> 44:43.333 align:start position:10% line:84.66% size:77.5% fascinating and one part pretty 44:43.333 --> 44:45.033 align:start position:10% line:84.66% size:75% scary is the idea that what we 44:45.033 --> 44:48.300 align:start position:10% line:84.66% size:67.5% do, not just that drugs can 44:48.300 --> 44:49.933 align:start position:10% line:84.66% size:65% effect the behavior of the 44:49.933 --> 44:51.533 align:start position:10% line:84.66% size:75% organism, and not just that it 44:51.533 --> 44:53.866 align:start position:10% line:84.66% size:67.5% can effect the chemistry in 44:53.866 --> 44:55.733 align:start position:10% line:84.66% size:80% different parts of the brain and 44:55.733 --> 44:58.333 align:start position:10% line:84.66% size:65% can effect how these cells 44:58.333 --> 44:59.700 align:start position:10% line:84.66% size:67.5% communicate to one another. 44:59.700 --> 45:01.433 align:start position:10% line:84.66% size:77.5% It can even effect the proteins 45:01.433 --> 45:03.366 align:start position:10% line:84.66% size:77.5% within the cell and change gene 45:03.366 --> 45:05.966 align:start position:10% line:84.66% size:77.5% transcription in which proteins 45:05.966 --> 45:07.933 align:start position:10% line:84.66% size:75% are actually going to be made. 45:07.933 --> 45:09.600 align:start position:10% line:84.66% size:77.5% Then it's possible for these to 45:09.600 --> 45:11.200 align:start position:10% line:84.66% size:60% be passed on to the next 45:11.200 --> 45:13.133 align:start position:10% line:84.66% size:27.5% generation. 45:13.133 --> 45:15.500 align:start position:10% line:84.66% size:80% Literally, what we consume, what 45:15.500 --> 45:19.666 align:start position:10% line:84.66% size:72.5% we eat, what we smoke, any of 45:19.666 --> 45:21.233 align:start position:10% line:84.66% size:62.5% these behaviors, might be 45:21.233 --> 45:22.700 align:start position:10% line:84.66% size:77.5% possible to be passed on to the 45:22.700 --> 45:24.300 align:start position:10% line:84.66% size:40% next generation. 45:24.300 --> 45:26.333 align:start position:10% line:84.66% size:72.5% This is a growing field and a 45:26.333 --> 45:27.533 align:start position:10% line:84.66% size:57.5% relatively new field of 45:27.533 --> 45:29.166 align:start position:10% line:84.66% size:30% epigenetics. 45:29.166 --> 45:31.133 align:start position:10% line:84.66% size:67.5% This Time article, I had to 45:31.133 --> 45:33.133 align:start position:10% line:84.66% size:77.5% feature it because I felt like, 45:33.133 --> 45:34.500 align:start position:10% line:84.66% size:72.5% in my mind, this is the first 45:34.500 --> 45:35.866 align:start position:10% line:84.66% size:80% time that epigenetics was really 45:35.866 --> 45:38.900 align:start position:10% line:84.66% size:70% put on a major public scale. 45:38.900 --> 45:40.800 align:start position:10% line:84.66% size:65% It made the cover of Time! 45:40.800 --> 45:43.300 align:start position:10% line:84.66% size:55% This was a story about 45:43.300 --> 45:46.333 align:start position:10% line:84.66% size:60% generations of families. 45:46.333 --> 45:48.133 align:start position:10% line:84.66% size:80% One generation of a family had a 45:48.133 --> 45:49.866 align:start position:10% line:84.66% size:77.5% time when there was very little 45:49.866 --> 45:52.100 align:start position:10% line:84.66% size:37.5% food available. 45:52.100 --> 45:53.666 align:start position:10% line:84.66% size:77.5% If they looked at the offspring 45:53.666 --> 45:57.366 align:start position:10% line:84.66% size:67.5% of the parents who had this 45:57.366 --> 45:59.833 align:start position:10% line:84.66% size:72.5% really low intake of food and 45:59.833 --> 46:01.500 align:start position:10% line:84.66% size:70% were essentially starving or 46:01.500 --> 46:02.933 align:start position:10% line:84.66% size:72.5% close to starving most of the 46:02.933 --> 46:04.766 align:start position:10% line:84.66% size:62.5% time, they found that the 46:04.766 --> 46:06.233 align:start position:10% line:84.66% size:77.5% children of those parents lived 46:06.233 --> 46:08.866 align:start position:10% line:84.66% size:70% significantly shorter lives. 46:08.866 --> 46:10.200 align:start position:10% line:84.66% size:72.5% Then when they looked at that 46:10.200 --> 46:11.766 align:start position:10% line:84.66% size:65% generation they found that 46:11.766 --> 46:13.366 align:start position:10% line:84.66% size:72.5% through a reversal and eating 46:13.366 --> 46:15.400 align:start position:10% line:84.66% size:65% excessively, that too, can 46:15.400 --> 46:16.900 align:start position:10% line:84.66% size:67.5% effect the life span of the 46:16.900 --> 46:18.633 align:start position:10% line:84.66% size:40% future children. 46:18.633 --> 46:20.000 align:start position:10% line:84.66% size:57.5% They started to look at 46:20.000 --> 46:21.200 align:start position:10% line:84.66% size:67.5% cross-generational studies. 46:21.200 --> 46:22.466 align:start position:10% line:84.66% size:75% That's something that's pretty 46:22.466 --> 46:24.500 align:start position:10% line:84.66% size:75% difficult to do in science and 46:24.500 --> 46:26.066 align:start position:10% line:84.66% size:75% with case studies because this 46:26.066 --> 46:28.000 align:start position:10% line:84.66% size:77.5% requires multigenerational time 46:28.000 --> 46:31.733 align:start position:10% line:84.66% size:20% periods. 46:31.733 --> 46:34.166 align:start position:10% line:84.66% size:75% When we talk about epigenetics 46:34.166 --> 46:36.000 align:start position:10% line:84.66% size:77.5% what we're talking about is not 46:36.000 --> 46:37.633 align:start position:10% line:84.66% size:67.5% changes to the actual genes 46:37.633 --> 46:38.833 align:start position:10% line:84.66% size:27.5% themselves. 46:38.833 --> 46:40.066 align:start position:10% line:84.66% size:62.5% This is not changing DNA. 46:40.066 --> 46:41.133 align:start position:10% line:84.66% size:57.5% We're not talking about 46:41.133 --> 46:42.333 align:start position:10% line:84.66% size:25% mutations. 46:42.333 --> 46:43.766 align:start position:10% line:84.66% size:67.5% We're not talking about the 46:43.766 --> 46:45.133 align:start position:10% line:84.66% size:15% X-Men. 46:45.133 --> 46:46.500 align:start position:10% line:84.66% size:75% We're not talking about things 46:46.500 --> 46:48.266 align:start position:10% line:84.66% size:72.5% that actually mutate the DNA. 46:48.266 --> 46:49.466 align:start position:10% line:84.66% size:57.5% We're talking about the 46:49.466 --> 46:51.166 align:start position:10% line:84.66% size:75% epigenome, which translates to 46:51.166 --> 46:53.100 align:start position:10% line:84.66% size:42.5% above the genome. 46:53.100 --> 46:54.600 align:start position:10% line:84.66% size:72.5% We're talking about chemicals 46:54.600 --> 46:56.833 align:start position:10% line:84.66% size:72.5% that can turn off or on genes 46:56.833 --> 46:58.333 align:start position:10% line:84.66% size:67.5% like a switch, like a light 46:58.333 --> 46:59.733 align:start position:10% line:84.66% size:17.5% switch. 46:59.733 --> 47:01.066 align:start position:10% line:84.66% size:80% They can actually, what's called 47:01.066 --> 47:02.566 align:start position:10% line:84.66% size:40% "silence" genes. 47:02.566 --> 47:04.200 align:start position:10% line:84.66% size:57.5% By chemicals binding to 47:04.200 --> 47:07.233 align:start position:10% line:84.66% size:75% different parts of the DNA, or 47:07.233 --> 47:08.800 align:start position:10% line:84.66% size:70% proteins affiliated with the 47:08.800 --> 47:10.500 align:start position:10% line:84.66% size:75% DNA, this can effectively shut 47:10.500 --> 47:13.666 align:start position:10% line:84.66% size:45% off certain genes. 47:13.666 --> 47:15.200 align:start position:10% line:84.66% size:72.5% It's possible for these to be 47:15.200 --> 47:19.133 align:start position:10% line:84.66% size:65% passed on through mitosis. 47:19.133 --> 47:20.700 align:start position:10% line:84.66% size:72.5% If we take this picture right 47:20.700 --> 47:22.166 align:start position:10% line:84.66% size:75% here we can see that this part 47:22.166 --> 47:23.633 align:start position:10% line:84.66% size:75% right here is the double helix 47:23.633 --> 47:25.233 align:start position:10% line:84.66% size:70% structure of DNA which we're 47:25.233 --> 47:27.233 align:start position:10% line:84.66% size:30% really fond. 47:27.233 --> 47:28.866 align:start position:10% line:84.66% size:67.5% It's the first thing that I 47:28.866 --> 47:30.466 align:start position:10% line:84.66% size:72.5% think of when I think of DNA. 47:30.466 --> 47:32.500 align:start position:10% line:84.66% size:70% I think of the double helix. 47:32.500 --> 47:35.366 align:start position:10% line:84.66% size:75% If we look at this long string 47:35.366 --> 47:37.333 align:start position:10% line:84.66% size:72.5% and we can see how it's wound 47:37.333 --> 47:39.600 align:start position:10% line:84.66% size:55% around these proteins. 47:39.600 --> 47:40.833 align:start position:10% line:84.66% size:62.5% These proteins are called 47:40.833 --> 47:42.966 align:start position:10% line:84.66% size:22.5% histones. 47:42.966 --> 47:44.100 align:start position:10% line:84.66% size:55% It actually gives this 47:44.100 --> 47:45.833 align:start position:10% line:84.66% size:80% appearance, with the DNA that is 47:45.833 --> 47:47.400 align:start position:10% line:84.66% size:77.5% literally wrapping around these 47:47.400 --> 47:48.566 align:start position:10% line:84.66% size:22.5% proteins. 47:48.566 --> 47:49.700 align:start position:10% line:84.66% size:77.5% This appearance is called beads 47:49.700 --> 47:50.966 align:start position:10% line:84.66% size:30% on a string. 47:50.966 --> 47:52.066 align:start position:10% line:84.66% size:67.5% Because that's actually the 47:52.066 --> 47:55.866 align:start position:10% line:84.66% size:72.5% structure that it appears as. 47:55.866 --> 47:57.833 align:start position:10% line:84.66% size:77.5% What happens is that before the 47:57.833 --> 48:01.333 align:start position:10% line:84.66% size:72.5% process of mitosis the DNA is 48:01.333 --> 48:03.000 align:start position:10% line:84.66% size:62.5% replicated, and it's also 48:03.000 --> 48:04.333 align:start position:10% line:84.66% size:25% condensed. 48:04.333 --> 48:05.900 align:start position:10% line:84.66% size:65% This area can be condensed 48:05.900 --> 48:08.366 align:start position:10% line:84.66% size:80% further and further, all the way 48:08.366 --> 48:09.933 align:start position:10% line:84.66% size:80% down, and get condensed into the 48:09.933 --> 48:11.500 align:start position:10% line:84.66% size:70% form of a chromosome so that 48:11.500 --> 48:16.966 align:start position:10% line:84.66% size:80% they can be copied, or split, if 48:16.966 --> 48:19.533 align:start position:10% line:84.66% size:77.5% you will, into different cells. 48:19.533 --> 48:22.300 align:start position:10% line:84.66% size:70% What can happen is two-fold. 48:22.300 --> 48:24.200 align:start position:10% line:84.66% size:77.5% There can be chemical tags that 48:24.200 --> 48:25.500 align:start position:10% line:84.66% size:75% can attach to the tails of the 48:25.500 --> 48:27.300 align:start position:10% line:84.66% size:80% histone, which are extensions of 48:27.300 --> 48:28.533 align:start position:10% line:84.66% size:30% the protein. 48:28.533 --> 48:30.100 align:start position:10% line:84.66% size:62.5% These tags can effect how 48:30.100 --> 48:32.933 align:start position:10% line:84.66% size:62.5% tightly the DNA is bound. 48:32.933 --> 48:34.400 align:start position:10% line:84.66% size:32.5% That matters. 48:34.400 --> 48:35.966 align:start position:10% line:84.66% size:75% If you look right here you can 48:35.966 --> 48:37.166 align:start position:10% line:84.66% size:72.5% see that this is an activated 48:37.166 --> 48:38.466 align:start position:10% line:84.66% size:12.5% gene. 48:38.466 --> 48:40.200 align:start position:10% line:84.66% size:77.5% A gene is a certain sub-unit of 48:40.200 --> 48:43.333 align:start position:10% line:84.66% size:72.5% DNA sequences that produces a 48:43.333 --> 48:46.100 align:start position:10% line:84.66% size:40% heritable trait. 48:46.100 --> 48:47.833 align:start position:10% line:84.66% size:72.5% Here's an activated gene that 48:47.833 --> 48:49.633 align:start position:10% line:84.66% size:77.5% any proteins or chemicals would 48:49.633 --> 48:51.933 align:start position:10% line:84.66% size:37.5% have access to. 48:51.933 --> 48:53.566 align:start position:10% line:84.66% size:65% But when the proteins come 48:53.566 --> 48:55.900 align:start position:10% line:84.66% size:72.5% together and are more tightly 48:55.900 --> 48:58.333 align:start position:10% line:84.66% size:65% condensed because of these 48:58.333 --> 49:00.233 align:start position:10% line:84.66% size:75% chemical markers, that gene is 49:00.233 --> 49:04.233 align:start position:10% line:84.66% size:30% now in here. 49:04.233 --> 49:06.400 align:start position:10% line:84.66% size:77.5% It's not assessable any longer. 49:06.400 --> 49:08.000 align:start position:10% line:84.66% size:70% It effectively silences that 49:08.000 --> 49:09.700 align:start position:10% line:84.66% size:80% gene, it's not allowed to now be 49:09.700 --> 49:11.833 align:start position:10% line:84.66% size:30% transcribed. 49:11.833 --> 49:13.400 align:start position:10% line:84.66% size:70% There are also methyl groups 49:13.400 --> 49:15.666 align:start position:10% line:84.66% size:67.5% that can bind to the actual 49:15.666 --> 49:17.433 align:start position:10% line:84.66% size:72.5% double helix itself, and also 49:17.433 --> 49:20.566 align:start position:10% line:84.66% size:70% silence that part of the DNA 49:20.566 --> 49:22.200 align:start position:10% line:84.66% size:22.5% sequence. 49:22.200 --> 49:23.700 align:start position:10% line:84.66% size:67.5% This is a way that, without 49:23.700 --> 49:25.466 align:start position:10% line:84.66% size:77.5% actually altering the structure 49:25.466 --> 49:27.700 align:start position:10% line:84.66% size:67.5% of DNA, with these changes, 49:27.700 --> 49:30.933 align:start position:10% line:84.66% size:80% parts of the genome can actually 49:30.933 --> 49:33.000 align:start position:10% line:84.66% size:30% be silenced. 49:33.000 --> 49:37.033 align:start position:10% line:84.66% size:77.5% That part can't be transcribed. 49:37.033 --> 49:39.000 align:start position:10% line:84.66% size:50% These are temporary. 49:39.000 --> 49:40.700 align:start position:10% line:84.66% size:52.5% These can be removed. 49:40.700 --> 49:41.833 align:start position:10% line:84.66% size:45% These are chemical 49:41.833 --> 49:43.200 align:start position:10% line:84.66% size:70% modifications, not an actual 49:43.200 --> 49:45.700 align:start position:10% line:84.66% size:70% change to the genome itself. 49:45.700 --> 49:47.133 align:start position:10% line:84.66% size:70% It is possible that they are 49:47.133 --> 49:48.533 align:start position:10% line:84.66% size:25% heritable. 49:48.533 --> 49:50.366 align:start position:10% line:84.66% size:75% I'm going to show you the next 49:50.366 --> 49:53.900 align:start position:10% line:84.66% size:70% piece of data, a set of data 49:53.900 --> 49:55.733 align:start position:10% line:84.66% size:80% from an experiment that suggests 49:55.733 --> 49:57.233 align:start position:10% line:84.66% size:80% that this might be heritable and 49:57.233 --> 49:59.000 align:start position:10% line:84.66% size:27.5% in mammals. 49:59.000 --> 50:00.400 align:start position:10% line:84.66% size:70% I think it's the first study 50:00.400 --> 50:02.866 align:start position:10% line:84.66% size:65% that actually showed this. 50:02.866 --> 50:04.433 align:start position:10% line:84.66% size:67.5% This causes changes in gene 50:04.433 --> 50:05.833 align:start position:10% line:84.66% size:70% expression, not to the genes 50:05.833 --> 50:07.566 align:start position:10% line:84.66% size:27.5% themselves. 50:07.566 --> 50:09.033 align:start position:10% line:84.66% size:75% This can be in response to any 50:09.033 --> 50:10.933 align:start position:10% line:84.66% size:80% slough of environmental changes, 50:10.933 --> 50:12.233 align:start position:10% line:84.66% size:45% both good and bad. 50:12.233 --> 50:13.800 align:start position:10% line:84.66% size:50% They're not all bad. 50:13.800 --> 50:16.666 align:start position:10% line:84.66% size:80% But certainly what we intake can 50:16.666 --> 50:18.233 align:start position:10% line:84.66% size:80% effect future generations, or at 50:18.233 --> 50:19.466 align:start position:10% line:84.66% size:65% least this is what this is 50:19.466 --> 50:22.300 align:start position:10% line:84.66% size:27.5% suggesting. 50:22.300 --> 50:24.366 align:start position:10% line:84.66% size:72.5% The first example of this was 50:24.366 --> 50:26.366 align:start position:10% line:84.66% size:80% looking at changes that occur in 50:26.366 --> 50:28.033 align:start position:10% line:84.66% size:20% mammals. 50:28.033 --> 50:29.633 align:start position:10% line:84.66% size:70% This experiment was designed 50:29.633 --> 50:31.633 align:start position:10% line:84.66% size:60% with two groups of mice. 50:31.633 --> 50:33.366 align:start position:10% line:84.66% size:77.5% One group of mice was kept in a 50:33.366 --> 50:35.066 align:start position:10% line:84.66% size:80% normal home cage and got to live 50:35.066 --> 50:36.900 align:start position:10% line:84.66% size:80% out their happy, little lives in 50:36.900 --> 50:38.500 align:start position:10% line:84.66% size:75% a normal home cage without any 50:38.500 --> 50:41.066 align:start position:10% line:84.66% size:80% special enrichment or treatment. 50:41.066 --> 50:42.466 align:start position:10% line:84.66% size:65% They're the control group. 50:42.466 --> 50:43.933 align:start position:10% line:84.66% size:62.5% Another set of mice where 50:43.933 --> 50:45.100 align:start position:10% line:84.66% size:60% exposed to what's called 50:45.100 --> 50:46.500 align:start position:10% line:84.66% size:62.5% environmental enrichment. 50:46.500 --> 50:48.066 align:start position:10% line:84.66% size:75% This is literally things like, 50:48.066 --> 50:49.700 align:start position:10% line:84.66% size:80% toys are placed in the home cage 50:49.700 --> 50:51.933 align:start position:10% line:84.66% size:72.5% and the mice get to play with 50:51.933 --> 50:53.233 align:start position:10% line:84.66% size:22.5% the toys. 50:53.233 --> 50:54.800 align:start position:10% line:84.66% size:60% They have exposure to an 50:54.800 --> 50:56.533 align:start position:10% line:84.66% size:75% enriched environment above and 50:56.533 --> 50:58.066 align:start position:10% line:84.66% size:70% beyond the typical home cage 50:58.066 --> 51:00.433 align:start position:10% line:84.66% size:30% environment. 51:00.433 --> 51:01.733 align:start position:10% line:84.66% size:77.5% This was done for this group of 51:01.733 --> 51:04.300 align:start position:10% line:84.66% size:75% mice for six hours per day for 51:04.300 --> 51:05.966 align:start position:10% line:84.66% size:20% 14 days. 51:05.966 --> 51:08.166 align:start position:10% line:84.66% size:57.5% So, just for two weeks. 51:08.166 --> 51:10.866 align:start position:10% line:84.66% size:75% Then they took that generation 51:10.866 --> 51:12.466 align:start position:10% line:84.66% size:77.5% of mice, both the control group 51:12.466 --> 51:14.066 align:start position:10% line:84.66% size:80% and the environmentally enriched 51:14.066 --> 51:15.733 align:start position:10% line:84.66% size:65% group, and they bred them. 51:15.733 --> 51:17.400 align:start position:10% line:84.66% size:80% They control group was bred with 51:17.400 --> 51:18.833 align:start position:10% line:84.66% size:27.5% each other. 51:18.833 --> 51:20.033 align:start position:10% line:84.66% size:70% The environmentally enriched 51:20.033 --> 51:21.300 align:start position:10% line:84.66% size:60% group was bred with each 51:21.300 --> 51:22.533 align:start position:10% line:84.66% size:15% other. 51:22.533 --> 51:23.733 align:start position:10% line:84.66% size:57.5% Then they looked at the 51:23.733 --> 51:26.266 align:start position:10% line:84.66% size:77.5% offspring of those mice who had 51:26.266 --> 51:27.800 align:start position:10% line:84.66% size:70% no exposure to environmental 51:27.800 --> 51:29.633 align:start position:10% line:84.66% size:55% enrichment whatsoever. 51:29.633 --> 51:30.833 align:start position:10% line:84.66% size:67.5% They had the same home cage 51:30.833 --> 51:31.966 align:start position:10% line:84.66% size:27.5% experience. 51:31.966 --> 51:33.166 align:start position:10% line:84.66% size:65% It was the same among both 51:33.166 --> 51:34.633 align:start position:10% line:84.66% size:17.5% groups. 51:34.633 --> 51:36.133 align:start position:10% line:84.66% size:80% What they did with these mice is 51:36.133 --> 51:37.533 align:start position:10% line:84.66% size:72.5% they looked at an area of the 51:37.533 --> 51:39.200 align:start position:10% line:84.66% size:72.5% brain called the hippocampus. 51:39.200 --> 51:41.566 align:start position:10% line:84.66% size:60% The hippocampus is where 51:41.566 --> 51:43.366 align:start position:10% line:84.66% size:50% memories are stored. 51:43.366 --> 51:46.366 align:start position:10% line:84.66% size:75% They looked at a common change 51:46.366 --> 51:48.166 align:start position:10% line:84.66% size:75% in electrical activity that is 51:48.166 --> 51:50.100 align:start position:10% line:84.66% size:62.5% really considered by most 51:50.100 --> 51:53.933 align:start position:10% line:84.66% size:72.5% scientists as the pinnacle of 51:53.933 --> 51:56.533 align:start position:10% line:84.66% size:80% learning within the hippocampus. 51:56.533 --> 51:58.166 align:start position:10% line:84.66% size:67.5% This is a phenomenon called 51:58.166 --> 52:00.933 align:start position:10% line:84.66% size:57.5% long-term potentiation. 52:00.933 --> 52:03.266 align:start position:10% line:84.66% size:80% Long-term potentiation is when a 52:03.266 --> 52:04.833 align:start position:10% line:84.66% size:60% really strong electrical 52:04.833 --> 52:07.166 align:start position:10% line:84.66% size:67.5% stimulus is applied with an 52:07.166 --> 52:09.733 align:start position:10% line:84.66% size:75% electrode into the hippocampus 52:09.733 --> 52:11.566 align:start position:10% line:84.66% size:72.5% or another part of the brain, 52:11.566 --> 52:13.700 align:start position:10% line:84.66% size:80% and that electrical stimulation, 52:13.700 --> 52:15.600 align:start position:10% line:84.66% size:77.5% which is shown here abbreviated 52:15.600 --> 52:17.433 align:start position:10% line:84.66% size:67.5% as theta burst stimulation. 52:17.433 --> 52:18.600 align:start position:10% line:84.66% size:67.5% It's a series of electrical 52:18.600 --> 52:19.666 align:start position:10% line:84.66% size:75% signals that are given in very 52:19.666 --> 52:21.800 align:start position:10% line:84.66% size:42.5% quick succession. 52:21.800 --> 52:23.366 align:start position:10% line:84.66% size:60% What happens is that the 52:23.366 --> 52:26.066 align:start position:10% line:84.66% size:70% electrical activity of those 52:26.066 --> 52:28.900 align:start position:10% line:84.66% size:75% neurons within the hippocampus 52:28.900 --> 52:30.733 align:start position:10% line:84.66% size:17.5% change. 52:30.733 --> 52:32.900 align:start position:10% line:84.66% size:65% Here they are at baseline. 52:32.900 --> 52:35.266 align:start position:10% line:84.66% size:80% Here, this arrow, shows when the 52:35.266 --> 52:36.666 align:start position:10% line:84.66% size:65% theta burst stimulation is 52:36.666 --> 52:37.866 align:start position:10% line:84.66% size:15% given. 52:37.866 --> 52:39.233 align:start position:10% line:84.66% size:80% What you can see is that there's 52:39.233 --> 52:40.700 align:start position:10% line:84.66% size:62.5% an actually elevation, or 52:40.700 --> 52:42.433 align:start position:10% line:84.66% size:77.5% potentiation, of the electrical 52:42.433 --> 52:44.533 align:start position:10% line:84.66% size:22.5% activity. 52:44.533 --> 52:46.133 align:start position:10% line:84.66% size:72.5% The electrical activity is no 52:46.133 --> 52:47.400 align:start position:10% line:84.66% size:30% longer here. 52:47.400 --> 52:49.500 align:start position:10% line:84.66% size:62.5% After the theta burst the 52:49.500 --> 52:51.333 align:start position:10% line:84.66% size:55% electrical activity is 52:51.333 --> 52:52.800 align:start position:10% line:84.66% size:70% potentiated above and beyond 52:52.800 --> 52:54.366 align:start position:10% line:84.66% size:45% baseline activity. 52:54.366 --> 52:55.700 align:start position:10% line:84.66% size:72.5% And it doesn't return back to 52:55.700 --> 52:56.966 align:start position:10% line:84.66% size:17.5% normal. 52:56.966 --> 52:58.200 align:start position:10% line:84.66% size:80% So it's not a quick spike up and 52:58.200 --> 53:00.100 align:start position:10% line:84.66% size:77.5% then a return back to baseline. 53:00.100 --> 53:01.600 align:start position:10% line:84.66% size:65% This potentiation actually 53:01.600 --> 53:03.733 align:start position:10% line:84.66% size:47.5% persists over time. 53:03.733 --> 53:06.266 align:start position:10% line:84.66% size:75% This is actually a hour later. 53:06.266 --> 53:07.833 align:start position:10% line:84.66% size:72.5% What the different colors are 53:07.833 --> 53:10.800 align:start position:10% line:84.66% size:72.5% showing is this black line is 53:10.800 --> 53:12.133 align:start position:10% line:84.66% size:72.5% from the animals that were in 53:12.133 --> 53:13.433 align:start position:10% line:84.66% size:35% the home cage. 53:13.433 --> 53:14.800 align:start position:10% line:84.66% size:60% They did not receive the 53:14.800 --> 53:16.066 align:start position:10% line:84.66% size:62.5% environmental enrichment. 53:16.066 --> 53:17.400 align:start position:10% line:84.66% size:52.5% This is of the parent 53:17.400 --> 53:18.766 align:start position:10% line:84.66% size:27.5% generation. 53:18.766 --> 53:20.500 align:start position:10% line:84.66% size:70% You can see right here, this 53:20.500 --> 53:22.400 align:start position:10% line:84.66% size:80% group right here actually has an 53:22.400 --> 53:24.966 align:start position:10% line:84.66% size:80% enhancement of the potentiation. 53:24.966 --> 53:27.066 align:start position:10% line:84.66% size:77.5% They have an enhanced long-term 53:27.066 --> 53:29.933 align:start position:10% line:84.66% size:67.5% potentiation that persists. 53:29.933 --> 53:31.566 align:start position:10% line:84.66% size:77.5% This is the group, in red, that 53:31.566 --> 53:33.100 align:start position:10% line:84.66% size:80% was exposed to the environmental 53:33.100 --> 53:35.866 align:start position:10% line:84.66% size:27.5% enrichment. 53:35.866 --> 53:38.233 align:start position:10% line:84.66% size:77.5% So environmental enrichment can 53:38.233 --> 53:39.833 align:start position:10% line:84.66% size:77.5% increase long-term potentiation 53:39.833 --> 53:42.466 align:start position:10% line:84.66% size:57.5% within the hippocampus. 53:42.466 --> 53:44.566 align:start position:10% line:84.66% size:65% It enhances plasticity, or 53:44.566 --> 53:46.100 align:start position:10% line:84.66% size:67.5% changes, within the neurons 53:46.100 --> 53:49.033 align:start position:10% line:84.66% size:57.5% within the hippocampus. 53:49.033 --> 53:50.600 align:start position:10% line:84.66% size:80% That's really what we're saying. 53:50.600 --> 53:52.366 align:start position:10% line:84.66% size:65% That's really interesting. 53:52.366 --> 53:53.800 align:start position:10% line:84.66% size:52.5% What I find even more 53:53.800 --> 53:55.133 align:start position:10% line:84.66% size:72.5% interesting is that these are 53:55.133 --> 53:57.366 align:start position:10% line:84.66% size:62.5% the children of those two 53:57.366 --> 53:59.400 align:start position:10% line:84.66% size:40% isolated groups. 53:59.400 --> 54:00.500 align:start position:10% line:84.66% size:80% These are the offspring, not the 54:00.500 --> 54:01.700 align:start position:10% line:84.66% size:22.5% children. 54:01.700 --> 54:02.900 align:start position:10% line:84.66% size:25% Excuse me. 54:02.900 --> 54:04.133 align:start position:10% line:84.66% size:72.5% They're the offspring of that 54:04.133 --> 54:05.400 align:start position:10% line:84.66% size:27.5% generation. 54:05.400 --> 54:06.666 align:start position:10% line:84.66% size:80% When we look at the offspring of 54:06.666 --> 54:08.466 align:start position:10% line:84.66% size:65% that generation who had no 54:08.466 --> 54:10.266 align:start position:10% line:84.66% size:80% environmental enrichment what we 54:10.266 --> 54:11.633 align:start position:10% line:84.66% size:80% can see is that in the offspring 54:11.633 --> 54:13.133 align:start position:10% line:84.66% size:62.5% of the parents who had no 54:13.133 --> 54:14.766 align:start position:10% line:84.66% size:75% environmental enrichment, this 54:14.766 --> 54:16.766 align:start position:10% line:84.66% size:72.5% is their potentiation levels. 54:16.766 --> 54:19.633 align:start position:10% line:84.66% size:75% In the animals who had parents 54:19.633 --> 54:21.466 align:start position:10% line:84.66% size:77.5% who were exposed to an enriched 54:21.466 --> 54:23.566 align:start position:10% line:84.66% size:75% environment, they didn't, just 54:23.566 --> 54:25.500 align:start position:10% line:84.66% size:67.5% the parents, we can find an 54:25.500 --> 54:26.933 align:start position:10% line:84.66% size:47.5% enhancement of this 54:26.933 --> 54:29.200 align:start position:10% line:84.66% size:32.5% potentiation. 54:29.200 --> 54:32.200 align:start position:10% line:84.66% size:70% The environment has been the 54:32.200 --> 54:34.400 align:start position:10% line:84.66% size:77.5% same for the offspring, but yet 54:34.400 --> 54:37.066 align:start position:10% line:84.66% size:77.5% the parent exposure actually is 54:37.066 --> 54:38.966 align:start position:10% line:84.66% size:70% changing the neural activity 54:38.966 --> 54:40.866 align:start position:10% line:84.66% size:70% within the part of the brain 54:40.866 --> 54:42.866 align:start position:10% line:84.66% size:52.5% important for memory. 54:42.866 --> 54:44.566 align:start position:10% line:84.66% size:72.5% This is, in my mind, a pretty 54:44.566 --> 54:46.600 align:start position:10% line:84.66% size:40% compelling case. 54:46.600 --> 54:48.566 align:start position:10% line:84.66% size:70% Also, if we reflect upon the 54:48.566 --> 54:51.500 align:start position:10% line:84.66% size:55% nature of addiction, a 54:51.500 --> 54:54.366 align:start position:10% line:84.66% size:75% potentially very scary finding 54:54.366 --> 54:55.833 align:start position:10% line:84.66% size:20% as well. 54:55.833 --> 54:57.200 align:start position:10% line:84.66% size:75% Not without hope, what it does 54:57.200 --> 54:58.833 align:start position:10% line:84.66% size:80% suggest is that the exposure, or 54:58.833 --> 55:01.200 align:start position:10% line:84.66% size:72.5% the life and exposures of the 55:01.200 --> 55:02.766 align:start position:10% line:84.66% size:77.5% parent, can be passed on to the 55:02.766 --> 55:04.666 align:start position:10% line:84.66% size:25% offspring. 55:04.666 --> 55:07.100 align:start position:10% line:84.66% size:77.5% This is compelling not just for 55:07.100 --> 55:09.000 align:start position:10% line:84.66% size:80% people that have been exposed to 55:09.000 --> 55:11.000 align:start position:10% line:84.66% size:72.5% drug use, but also for people 55:11.000 --> 55:12.400 align:start position:10% line:84.66% size:45% who are abstinent. 55:12.400 --> 55:13.733 align:start position:10% line:84.66% size:77.5% Perhaps some of the changes may 55:13.733 --> 55:15.866 align:start position:10% line:84.66% size:77.5% not be solidified or passed on. 55:15.866 --> 55:18.933 align:start position:10% line:84.66% size:72.5% Now this is not a for sure in 55:18.933 --> 55:20.300 align:start position:10% line:84.66% size:55% human experimentation. 55:20.300 --> 55:22.166 align:start position:10% line:84.66% size:60% This is looking at mice. 55:22.166 --> 55:24.133 align:start position:10% line:84.66% size:75% But it is the first suggestion 55:24.133 --> 55:26.200 align:start position:10% line:84.66% size:65% of heritable, inheritated, 55:26.200 --> 55:29.900 align:start position:10% line:84.66% size:77.5% epigenetics changes in mammals. 55:29.900 --> 55:35.666 align:start position:10% line:84.66% size:80% When we think about the learning 55:35.666 --> 55:37.600 align:start position:10% line:84.66% size:72.5% that is involved in addiction 55:37.600 --> 55:39.233 align:start position:10% line:84.66% size:72.5% and we look at it across this 55:39.233 --> 55:40.866 align:start position:10% line:84.66% size:75% level, we can see that this is 55:40.866 --> 55:42.833 align:start position:10% line:84.66% size:80% not just effecting the behavior, 55:42.833 --> 55:44.733 align:start position:10% line:84.66% size:70% but it's effecting the whole 55:44.733 --> 55:46.733 align:start position:10% line:84.66% size:70% organism, in most cases, the 55:46.733 --> 55:49.333 align:start position:10% line:84.66% size:15% human. 55:49.333 --> 55:50.966 align:start position:10% line:84.66% size:77.5% This is also looking at certain 55:50.966 --> 55:52.266 align:start position:10% line:84.66% size:47.5% areas of the brain. 55:52.266 --> 55:53.833 align:start position:10% line:84.66% size:77.5% Within those areas of the brain 55:53.833 --> 55:55.566 align:start position:10% line:84.66% size:55% the cells are changed. 55:55.566 --> 55:57.200 align:start position:10% line:84.66% size:80% The chemicals that the cells use 55:57.200 --> 55:59.466 align:start position:10% line:84.66% size:67.5% to communicate are changed. 55:59.466 --> 56:01.766 align:start position:10% line:84.66% size:80% The proteins inside the cell and 56:01.766 --> 56:03.033 align:start position:10% line:84.66% size:60% on the cell membrane are 56:03.033 --> 56:04.400 align:start position:10% line:84.66% size:20% altered. 56:04.400 --> 56:05.733 align:start position:10% line:84.66% size:70% And these alterations can be 56:05.733 --> 56:09.433 align:start position:10% line:84.66% size:80% long-lasting even in abstinence, 56:09.433 --> 56:11.200 align:start position:10% line:84.66% size:72.5% and even possibly to the next 56:11.200 --> 56:13.533 align:start position:10% line:84.66% size:27.5% generation. 56:13.533 --> 56:17.233 align:start position:10% line:84.66% size:67.5% In my mind this is a pretty 56:17.233 --> 56:18.900 align:start position:10% line:84.66% size:77.5% compelling set of evidence that 56:18.900 --> 56:21.933 align:start position:10% line:84.66% size:70% suggests a multi-level, or a 56:21.933 --> 56:23.466 align:start position:10% line:84.66% size:77.5% systems approach to the changes 56:23.466 --> 56:24.666 align:start position:10% line:84.66% size:75% that addiction can have on the 56:24.666 --> 56:26.166 align:start position:10% line:84.66% size:12.5% body. 56:26.166 --> 56:27.433 align:start position:10% line:84.66% size:52.5% These changes are not 56:27.433 --> 56:28.700 align:start position:10% line:84.66% size:30% short-lived. 56:28.700 --> 56:30.933 align:start position:10% line:84.66% size:70% They're actually persistent, 56:30.933 --> 56:32.433 align:start position:10% line:84.66% size:72.5% making treatment particularly 56:32.433 --> 56:33.800 align:start position:10% line:84.66% size:25% difficult. 56:33.800 --> 56:35.466 align:start position:10% line:84.66% size:72.5% If these neural changes still 56:35.466 --> 56:36.933 align:start position:10% line:84.66% size:70% persist despite treatment, a 56:36.933 --> 56:38.300 align:start position:10% line:84.66% size:72.5% person may still find it very 56:38.300 --> 56:40.500 align:start position:10% line:84.66% size:80% difficult to maintain abstinence 56:40.500 --> 56:42.066 align:start position:10% line:84.66% size:72.5% for any significant period of 56:42.066 --> 56:43.566 align:start position:10% line:84.66% size:12.5% time. 56:43.566 --> 56:45.166 align:start position:10% line:84.66% size:77.5% Their brain has not, literally, 56:45.166 --> 56:46.700 align:start position:10% line:84.66% size:77.5% caught up to the changes in the 56:46.700 --> 56:49.266 align:start position:10% line:84.66% size:60% lifestyle, or changes in 56:49.266 --> 56:52.600 align:start position:10% line:84.66% size:22.5% exposure. 56:52.600 --> 56:54.733 align:start position:10% line:84.66% size:77.5% If we think about modifying old 56:54.733 --> 56:56.433 align:start position:10% line:84.66% size:75% messages, I remember these old 56:56.433 --> 56:58.033 align:start position:10% line:84.66% size:77.5% commercials about, this is your 56:58.033 --> 56:59.300 align:start position:10% line:84.66% size:77.5% brain and this is your brain on 56:59.300 --> 57:00.366 align:start position:10% line:84.66% size:15% drugs. 57:00.366 --> 57:01.500 align:start position:10% line:84.66% size:67.5% Remember these commercials? 57:01.500 --> 57:02.900 align:start position:10% line:84.66% size:75% I have a very strong memory of 57:02.900 --> 57:04.400 align:start position:10% line:84.66% size:45% these commercials. 57:04.400 --> 57:05.566 align:start position:10% line:84.66% size:70% We can really think of it as 57:05.566 --> 57:07.000 align:start position:10% line:84.66% size:37.5% modifying this. 57:07.000 --> 57:08.833 align:start position:10% line:84.66% size:77.5% We can say, this is your brain, 57:08.833 --> 57:10.766 align:start position:10% line:84.66% size:75% with lots of connections and a 57:10.766 --> 57:12.966 align:start position:10% line:84.66% size:67.5% variety of neuron to neuron 57:12.966 --> 57:14.633 align:start position:10% line:84.66% size:72.5% connections within the brain. 57:14.633 --> 57:15.833 align:start position:10% line:84.66% size:72.5% We can think of, this is your 57:15.833 --> 57:17.400 align:start position:10% line:84.66% size:37.5% brain on drugs. 57:17.400 --> 57:18.966 align:start position:10% line:84.66% size:77.5% Not as many connections, but of 57:18.966 --> 57:20.766 align:start position:10% line:84.66% size:72.5% the connections that persist, 57:20.766 --> 57:22.200 align:start position:10% line:84.66% size:77.5% they're very active and they're 57:22.200 --> 57:25.933 align:start position:10% line:84.66% size:62.5% very honed and specified. 57:25.933 --> 57:28.166 align:start position:10% line:84.66% size:75% This creates a way of thinking 57:28.166 --> 57:29.566 align:start position:10% line:84.66% size:75% about the disease of addiction 57:29.566 --> 57:31.733 align:start position:10% line:84.66% size:70% as really a hijack of normal 57:31.733 --> 57:35.433 align:start position:10% line:84.66% size:80% learning within the human brain. 57:35.433 --> 57:36.700 align:start position:10% line:84.66% size:60% So I leave that with any 57:36.700 --> 57:38.500 align:start position:10% line:84.66% size:25% questions. 57:38.500 --> 57:40.500 align:start position:10% line:84.66% size:25% [applause]