1 00:00:00,250 --> 00:00:01,800 The following content is provided 2 00:00:01,800 --> 00:00:04,040 under a Creative Commons license. 3 00:00:04,040 --> 00:00:06,890 Your support will help MIT OpenCourseWare continue 4 00:00:06,890 --> 00:00:10,740 to offer high quality educational resources for free. 5 00:00:10,740 --> 00:00:13,360 To make a donation or view additional materials 6 00:00:13,360 --> 00:00:17,241 from hundreds of MIT courses, visit MIT OpenCourseWare 7 00:00:17,241 --> 00:00:17,866 at ocw.mit.edu. 8 00:00:22,980 --> 00:00:27,109 PROFESSOR: OK, I just wanted to go back over a few things 9 00:00:27,109 --> 00:00:28,900 to make sure you're understanding it right. 10 00:00:28,900 --> 00:00:32,350 When I talked about this anatomical plasticity 11 00:00:32,350 --> 00:00:36,190 in the hippocampus, you just have 12 00:00:36,190 --> 00:00:40,880 to realize that every one of these rectangles 13 00:00:40,880 --> 00:00:44,990 represents the very same slice, just showing 14 00:00:44,990 --> 00:00:49,480 different things in the same little bit of the-- 15 00:00:49,480 --> 00:00:51,470 as you see here. 16 00:00:51,470 --> 00:00:58,040 It shows a slice in the dentate gyrus 17 00:00:58,040 --> 00:01:02,410 but just through the dendrites of the dentate gyrus 18 00:01:02,410 --> 00:01:07,020 from the peel surface down to the cell bodies. 19 00:01:07,020 --> 00:01:09,116 So here it's showing one kind of connection, 20 00:01:09,116 --> 00:01:10,990 here it's showing another kind of connection, 21 00:01:10,990 --> 00:01:13,960 and it shows what happens if you remove one of them. 22 00:01:13,960 --> 00:01:15,760 You get [? sprouting ?] of the other one. 23 00:01:15,760 --> 00:01:16,666 Yes? 24 00:01:16,666 --> 00:01:17,572 AUDIENCE: [INAUDIBLE] 25 00:01:21,600 --> 00:01:24,760 PROFESSOR: It means that this particular projection doesn't 26 00:01:24,760 --> 00:01:30,980 go there, but the projection here from the entorhinal cortex 27 00:01:30,980 --> 00:01:33,060 doesn't terminate in the inner part 28 00:01:33,060 --> 00:01:34,730 of the dendrite near the cell body. 29 00:01:34,730 --> 00:01:41,040 It terminates in the outer 2/3 whereas the association 30 00:01:41,040 --> 00:01:43,290 fibers coming from other parts of the hippocampus, 31 00:01:43,290 --> 00:01:45,860 they terminate in that area. 32 00:01:45,860 --> 00:01:49,850 So in that rectangle is white, the upper 2/3 is white. 33 00:01:53,970 --> 00:01:56,280 So obviously there's some kind of specificity 34 00:01:56,280 --> 00:01:57,920 in the way those terminals grow in. 35 00:02:00,570 --> 00:02:03,870 Maybe in development they do overlap, but in the adult, 36 00:02:03,870 --> 00:02:05,030 they don't. 37 00:02:05,030 --> 00:02:08,930 But then if you remove one of them, 38 00:02:08,930 --> 00:02:11,830 the other one will sprout. 39 00:02:11,830 --> 00:02:14,300 And I'm only showing true projections. 40 00:02:14,300 --> 00:02:18,184 There are other projections like the acetylcholine axons coming 41 00:02:18,184 --> 00:02:18,850 from the septum. 42 00:02:18,850 --> 00:02:23,890 They change too after you make one 43 00:02:23,890 --> 00:02:28,110 or another lesions of these [INAUDIBLE]. 44 00:02:28,110 --> 00:02:31,950 OK and then the point about this more modulatory 45 00:02:31,950 --> 00:02:38,950 states and how it changes with different stages of sleep 46 00:02:38,950 --> 00:02:42,520 postulated to really change the flow of information 47 00:02:42,520 --> 00:02:45,570 between the hippocampus and the neocortex. 48 00:02:45,570 --> 00:02:48,100 I just wanted to point out that we 49 00:02:48,100 --> 00:02:53,250 know that these are only three of the modulators that 50 00:02:53,250 --> 00:02:55,910 can change the state of the brain. 51 00:02:55,910 --> 00:02:59,740 So if this theory is correct, and probably 52 00:02:59,740 --> 00:03:03,770 is at least partly correct, it just 53 00:03:03,770 --> 00:03:07,750 indicates that when brain state changes, can pretty drastically 54 00:03:07,750 --> 00:03:09,560 change the way connections are working 55 00:03:09,560 --> 00:03:13,040 where the information is flowing in the cortex. 56 00:03:13,040 --> 00:03:15,540 And remember when we-- in chapter 17, 57 00:03:15,540 --> 00:03:18,000 I talked about how many different possible brain 58 00:03:18,000 --> 00:03:19,150 states there are. 59 00:03:22,320 --> 00:03:25,030 It means this kind-- this is just 60 00:03:25,030 --> 00:03:28,870 the beginning of this kind of model 61 00:03:28,870 --> 00:03:32,970 to represent information flow in neocortex. 62 00:03:32,970 --> 00:03:33,914 AUDIENCE: [INAUDIBLE] 63 00:03:37,220 --> 00:03:38,070 PROFESSOR: Sure. 64 00:03:38,070 --> 00:03:39,032 AUDIENCE: [INAUDIBLE] 65 00:03:46,740 --> 00:03:47,902 PROFESSOR: That's right. 66 00:03:47,902 --> 00:03:48,866 AUDIENCE: [INAUDIBLE] 67 00:03:56,110 --> 00:04:01,920 PROFESSOR: Yes, in fact, in REM sleep, 68 00:04:01,920 --> 00:04:04,470 it doesn't mean there's nothing important going on. 69 00:04:04,470 --> 00:04:06,640 We know that dreaming is occurring. 70 00:04:06,640 --> 00:04:09,340 You know, people argue all the time 71 00:04:09,340 --> 00:04:13,480 about what the function of that might be. 72 00:04:13,480 --> 00:04:16,540 We also know that if you're in dream sleep, 73 00:04:16,540 --> 00:04:21,199 when you're awakened, you tend not to remember. 74 00:04:24,320 --> 00:04:25,970 You can train yourself to remember, 75 00:04:25,970 --> 00:04:27,680 because if you keep it in mind, you 76 00:04:27,680 --> 00:04:32,280 keep rehearsing after you get up, you can report a dream. 77 00:04:32,280 --> 00:04:34,850 And that's why in studies of dreams, 78 00:04:34,850 --> 00:04:38,430 it's not very reliable to talk about somebody a half hour 79 00:04:38,430 --> 00:04:42,310 later after they get up, because they will forget most of it. 80 00:04:42,310 --> 00:04:45,160 So that has something to do with these states too. 81 00:04:45,160 --> 00:04:48,370 But there's really a lot that we just don't understand, 82 00:04:48,370 --> 00:04:50,800 but we do know that there's different states 83 00:04:50,800 --> 00:04:53,870 of our consciousness where we don't-- there's a lot 84 00:04:53,870 --> 00:04:57,770 of dissociation between. 85 00:04:57,770 --> 00:05:00,640 And in abnormal cases, you can get more than one 86 00:05:00,640 --> 00:05:04,660 personality existing in the same person, 87 00:05:04,660 --> 00:05:07,920 the same central nervous system. 88 00:05:07,920 --> 00:05:10,740 That has to involve these different kinds of space, 89 00:05:10,740 --> 00:05:13,220 but we don't understand the brain mechanisms 90 00:05:13,220 --> 00:05:16,520 behind that kind of dissociation. 91 00:05:16,520 --> 00:05:17,020 Yes? 92 00:05:17,020 --> 00:05:17,974 AUDIENCE: [INAUDIBLE] 93 00:05:33,256 --> 00:05:34,630 PROFESSOR: You would like to know 94 00:05:34,630 --> 00:05:39,910 what the neurochemical coeruleus are, and I can't tell you. 95 00:05:39,910 --> 00:05:43,890 You can look in the lecture to see if anybody's even tried. 96 00:05:43,890 --> 00:05:47,280 And since you can get REM sleep in animals, 97 00:05:47,280 --> 00:05:50,795 you can do these REM sleep deprivation studies in animals, 98 00:05:50,795 --> 00:05:52,420 it seems to me that you could certainly 99 00:05:52,420 --> 00:05:54,580 look for things like that. 100 00:05:54,580 --> 00:05:57,342 There might even be changes in the cerebral spinal fluid. 101 00:06:00,580 --> 00:06:04,130 As we know, you can inject cerebral spinal fluid 102 00:06:04,130 --> 00:06:06,890 from one animal that's sleeping to an animal that's not, 103 00:06:06,890 --> 00:06:09,310 and the animal that's not will go to sleep. 104 00:06:09,310 --> 00:06:12,810 So we know there are effects even there, 105 00:06:12,810 --> 00:06:17,780 but that kind of research is just not done. 106 00:06:25,240 --> 00:06:27,710 One of the things that neuroscience like to-- people 107 00:06:27,710 --> 00:06:28,710 work on what's popular. 108 00:06:31,360 --> 00:06:33,980 It takes an enterprising graduate student to dive 109 00:06:33,980 --> 00:06:35,150 into something like that. 110 00:06:39,430 --> 00:06:41,110 These pictures of the human brain 111 00:06:41,110 --> 00:06:46,170 are just to help orient you to these same structures 112 00:06:46,170 --> 00:06:47,080 in our own brains. 113 00:06:52,165 --> 00:06:56,470 You can begin to see why we use these rodents. 114 00:06:56,470 --> 00:06:59,200 They're much more like the embryonic human brain, 115 00:06:59,200 --> 00:07:01,280 because the human brains have grown so big 116 00:07:01,280 --> 00:07:03,810 and the cortex, especially, has grown so big 117 00:07:03,810 --> 00:07:06,900 that it distorts the whole appearance. 118 00:07:06,900 --> 00:07:11,420 This here shows the hippocampal formation in fornix, 119 00:07:11,420 --> 00:07:16,500 and the part of the hypothalamus memory body 120 00:07:16,500 --> 00:07:19,470 where the fornix terminates. 121 00:07:19,470 --> 00:07:22,160 And you can't tell from a picture like that, 122 00:07:22,160 --> 00:07:24,780 but this is definitely the brain stem, 123 00:07:24,780 --> 00:07:27,212 the upper brain stem and this is up in the hemisphere, 124 00:07:27,212 --> 00:07:29,920 but in fact, that's what it represents. 125 00:07:29,920 --> 00:07:34,550 And I just sketched here the hippocampus anterior, 126 00:07:34,550 --> 00:07:38,440 posterior, and the fibers of the fimbria 127 00:07:38,440 --> 00:07:40,990 in the fornix coming out of the hippocampus 128 00:07:40,990 --> 00:07:43,800 and becoming the columns of fornix here. 129 00:07:43,800 --> 00:07:47,237 I don't show the ones that go into the septal area which 130 00:07:47,237 --> 00:07:48,690 would be right there. 131 00:07:48,690 --> 00:07:52,090 I do show the commissure [INAUDIBLE]. 132 00:07:52,090 --> 00:07:59,070 OK and then this is a little more like a rodent, 133 00:07:59,070 --> 00:08:02,575 but this picture was a reconstruction published 134 00:08:02,575 --> 00:08:06,570 in a human neuroanatomy book by Nolte 135 00:08:06,570 --> 00:08:11,970 which tries to depict the human hippocampus. 136 00:08:11,970 --> 00:08:18,277 And it's not too hard to see the close relationship, 137 00:08:18,277 --> 00:08:20,110 but the same structures we see in the rodent 138 00:08:20,110 --> 00:08:21,510 we can find in a human. 139 00:08:25,345 --> 00:08:31,163 I want to talk about the limbic-- other parts 140 00:08:31,163 --> 00:08:34,220 of the limbic forebrain other than hippocampus 141 00:08:34,220 --> 00:08:37,299 in the hypothalamus, especially the amygdala 142 00:08:37,299 --> 00:08:39,110 and the basal forebrain. 143 00:08:39,110 --> 00:08:43,140 They're closely related to each other. 144 00:08:43,140 --> 00:08:50,630 This is Chapter 29 in the book. 145 00:08:53,680 --> 00:08:56,570 Let's just review a couple terms to start with. 146 00:08:56,570 --> 00:09:00,010 Where does that term rhinencephalon come from? 147 00:09:00,010 --> 00:09:00,760 What does it mean? 148 00:09:04,750 --> 00:09:08,080 It means nose brain. 149 00:09:08,080 --> 00:09:11,490 Well that was an old term used for all these structures 150 00:09:11,490 --> 00:09:14,190 that we now say are the limbric endbrain. 151 00:09:21,640 --> 00:09:23,900 The term limbic system didn't start 152 00:09:23,900 --> 00:09:30,460 to be used until after Papez's publication and then interest 153 00:09:30,460 --> 00:09:35,010 that that engendered from other anatomists. 154 00:09:35,010 --> 00:09:38,230 The neuron anatomists began specifically 155 00:09:38,230 --> 00:09:43,970 studying these connections, especially with Nauta 156 00:09:43,970 --> 00:09:46,610 introducing a more sensitive method 157 00:09:46,610 --> 00:09:49,240 for studying connections in animals. 158 00:09:49,240 --> 00:09:51,080 We talked about that in chapter-- way 159 00:09:51,080 --> 00:09:54,550 back in the beginning, Chapter 2. 160 00:09:54,550 --> 00:09:57,360 And now, of course, we have many, even more sensitive, 161 00:09:57,360 --> 00:10:03,850 methods involving various tracer substances. 162 00:10:03,850 --> 00:10:05,810 But anyway, this is the Papez story, 163 00:10:05,810 --> 00:10:09,500 and I just point out here that some anatomy books, including 164 00:10:09,500 --> 00:10:17,450 one that I've often made use of, [INAUDIBLE], 165 00:10:17,450 --> 00:10:19,720 he-- in an earlier version of this book 166 00:10:19,720 --> 00:10:22,490 he had this nice description of Papez's work, 167 00:10:22,490 --> 00:10:26,190 and then in the third edition he eliminated. 168 00:10:26,190 --> 00:10:27,550 The question is why? 169 00:10:27,550 --> 00:10:30,530 Well he was trying to get rid of a lot of the history, 170 00:10:30,530 --> 00:10:33,170 because he didn't want the book to be too long. 171 00:10:33,170 --> 00:10:35,470 So lend it to what medical students will read. 172 00:10:39,120 --> 00:10:40,630 But there are other reasons too. 173 00:10:44,320 --> 00:10:46,930 There's different kinds of grandmasters. 174 00:10:46,930 --> 00:10:51,030 Some of them are more interested in the structures, where 175 00:10:51,030 --> 00:10:53,100 they live, how you can separate them. 176 00:10:55,970 --> 00:11:00,620 But they don't focus on the connections as much. 177 00:11:00,620 --> 00:11:02,400 Neurologists too. 178 00:11:02,400 --> 00:11:04,520 We don't know enough about functions, 179 00:11:04,520 --> 00:11:08,480 and they don't want to try to group things. 180 00:11:13,150 --> 00:11:18,740 So it's really the people, the Nauta type of people-- 181 00:11:18,740 --> 00:11:22,140 and there's a lot of us, because now they 182 00:11:22,140 --> 00:11:24,430 train a number of people, and we've 183 00:11:24,430 --> 00:11:31,350 trained additional people-- that had led me and other people 184 00:11:31,350 --> 00:11:35,370 to sort of talk more about [? Papez ?] 185 00:11:35,370 --> 00:11:38,490 and the limbic system in general. 186 00:11:38,490 --> 00:11:41,100 Remember that [? Papez ?] took that term, 187 00:11:41,100 --> 00:11:43,870 rhinencephalon, and analyzed it and said 188 00:11:43,870 --> 00:11:47,130 a lot of these structures aren't actually involved in olfaction 189 00:11:47,130 --> 00:11:49,910 from the human clinical cases that he was familiar with. 190 00:11:49,910 --> 00:11:56,570 This was back in the 1920s and 30s. 191 00:11:56,570 --> 00:12:00,160 But he did find that all of these structures 192 00:12:00,160 --> 00:12:02,740 were involved in seizures that affected 193 00:12:02,740 --> 00:12:05,610 the motion and that autonomic nervous system. 194 00:12:09,540 --> 00:12:12,980 So he said it seemed to be an interconnected-- he could 195 00:12:12,980 --> 00:12:18,714 define what he called an interconnected serious of cell 196 00:12:18,714 --> 00:12:20,380 groups that were concerned with feelings 197 00:12:20,380 --> 00:12:21,680 and emotional expressions. 198 00:12:21,680 --> 00:12:24,800 He emphasized that aspect of it. 199 00:12:24,800 --> 00:12:28,670 He could have added autonomic changes. 200 00:12:28,670 --> 00:12:34,830 But what it led to was new thinking about our ability 201 00:12:34,830 --> 00:12:39,480 to group structures according to relationships 202 00:12:39,480 --> 00:12:42,720 in their connections, and that led 203 00:12:42,720 --> 00:12:45,620 to a colleague of Nauta's, Paul [? McCrane ?] 204 00:12:45,620 --> 00:12:50,040 at NIH giving the system a name, the limbic system. 205 00:12:50,040 --> 00:12:55,290 He based that on Broca's term from the 19th century. 206 00:12:55,290 --> 00:13:00,150 We talked about the great limbic lobe. 207 00:13:00,150 --> 00:13:03,850 And we've seen that in the medial views 208 00:13:03,850 --> 00:13:04,900 of the human brain. 209 00:13:07,640 --> 00:13:10,030 And more recently, the reason for a lot 210 00:13:10,030 --> 00:13:12,050 of revival of interest, of course, 211 00:13:12,050 --> 00:13:16,080 is because we know it extends-- the functions 212 00:13:16,080 --> 00:13:20,840 of this interconnected system extends beyond mood and emotion 213 00:13:20,840 --> 00:13:23,595 plays a major role in spatial cognition 214 00:13:23,595 --> 00:13:27,105 and the formations of specific memory for places and events 215 00:13:27,105 --> 00:13:32,870 in our lives, not just in humans of course but in animals too. 216 00:13:38,380 --> 00:13:43,975 This is the Papez circuit, slide we saw before. 217 00:13:47,370 --> 00:13:52,290 Papez described these structures that you see in red here 218 00:13:52,290 --> 00:13:56,240 and the network diagram that I made up 219 00:13:56,240 --> 00:14:03,000 where I was trying to include more recent findings of how 220 00:14:03,000 --> 00:14:07,190 these structures are related to each other. 221 00:14:07,190 --> 00:14:12,070 Some of them are exactly as Papez described, mammary bodies 222 00:14:12,070 --> 00:14:14,630 to anterior nuclei to the thalamus 223 00:14:14,630 --> 00:14:17,090 to the cingulate cortex. 224 00:14:17,090 --> 00:14:20,430 Now in Papez's time, cingulate included 225 00:14:20,430 --> 00:14:23,230 some of the more caudal areas that now are often 226 00:14:23,230 --> 00:14:25,992 named differently, the retrosplenial cortex 227 00:14:25,992 --> 00:14:29,380 and other paralimbic areas that extend 228 00:14:29,380 --> 00:14:32,910 right down to the entorhinal cortex. 229 00:14:32,910 --> 00:14:36,970 He, of course, separated the entorhinal area 230 00:14:36,970 --> 00:14:45,600 from the cingulate, but what looks like posterior cingulate, 231 00:14:45,600 --> 00:14:47,590 posterior, part of a singular gyrus 232 00:14:47,590 --> 00:14:51,010 we now call retrosplenial cortex. 233 00:14:51,010 --> 00:14:56,910 And there's some other names too used for components of it. 234 00:14:56,910 --> 00:15:02,950 OK and then I'm showing how from the hippocampus itself, 235 00:15:02,950 --> 00:15:06,545 there are connections, back to the mammary bodies 236 00:15:06,545 --> 00:15:09,670 that Papez knew about. 237 00:15:09,670 --> 00:15:12,690 Remember, he didn't have the methods to know what was direct 238 00:15:12,690 --> 00:15:15,660 and what was indirect, but he did see that bundle. 239 00:15:15,660 --> 00:15:18,170 You could even trace them into sections, 240 00:15:18,170 --> 00:15:20,262 and you could follow that bundle all the way 241 00:15:20,262 --> 00:15:21,220 to the mammary bundles. 242 00:15:21,220 --> 00:15:24,015 But now we know there are many other connections 243 00:15:24,015 --> 00:15:26,990 of those axons as I've shown here. 244 00:15:26,990 --> 00:15:31,320 So what's dominant input if it's not olfaction 245 00:15:31,320 --> 00:15:33,790 as Papez realized? 246 00:15:33,790 --> 00:15:35,330 You can't just say, well emotions 247 00:15:35,330 --> 00:15:37,790 are the dominant input. 248 00:15:37,790 --> 00:15:39,540 Feelings are the dominant input. 249 00:15:39,540 --> 00:15:46,430 That's crossing realms here from behavior to anatomy. 250 00:15:46,430 --> 00:15:51,190 I want to know anatomically, what's the dominant input? 251 00:15:51,190 --> 00:15:56,080 Well in mammals the dominant input is here. 252 00:15:56,080 --> 00:16:05,020 It comes from the neocortex, because these association 253 00:16:05,020 --> 00:16:08,010 areas, particularly the multimodal association 254 00:16:08,010 --> 00:16:13,640 areas, the areas that have grown the most in the more 255 00:16:13,640 --> 00:16:21,870 recent human evolution, and in that period 256 00:16:21,870 --> 00:16:25,680 our brains have almost doubled in size. 257 00:16:25,680 --> 00:16:29,426 They are closely connected to singular areas, 258 00:16:29,426 --> 00:16:32,340 retrosplenial cortex and other paralimbic areas 259 00:16:32,340 --> 00:16:35,600 and to the entorhinal cortex. 260 00:16:35,600 --> 00:16:38,392 And often you will see in textbooks 261 00:16:38,392 --> 00:16:41,780 that this projection of entorhinal area 262 00:16:41,780 --> 00:16:47,310 into the dentate is the dominant input. 263 00:16:47,310 --> 00:16:50,410 I point out here that there's connections to the subiculum 264 00:16:50,410 --> 00:16:50,950 as well. 265 00:16:53,910 --> 00:16:59,090 But the dominant input, by way of these paralimbic structures 266 00:16:59,090 --> 00:17:00,005 comes from neocortex. 267 00:17:03,120 --> 00:17:05,109 The 268 00:17:05,109 --> 00:17:08,495 So now how do we get from neocortex to the hypothalamus? 269 00:17:11,450 --> 00:17:14,560 I'm asking here, what are the most direct routes, 270 00:17:14,560 --> 00:17:19,109 monosynaptic and disynaptic from neocortex to hypothalamus. 271 00:17:19,109 --> 00:17:21,750 Well you can look at the page circuit diagram 272 00:17:21,750 --> 00:17:28,210 and see their connections, but not so direct 273 00:17:28,210 --> 00:17:32,600 between neocortex and hypothalamus 274 00:17:32,600 --> 00:17:35,380 seen those diagrams. 275 00:17:35,380 --> 00:17:38,360 But I've taken Mycelium's box diagrams 276 00:17:38,360 --> 00:17:45,550 where he's depicting transcortical connections 277 00:17:45,550 --> 00:17:47,845 from the most specialized cortical areas, 278 00:17:47,845 --> 00:17:51,230 the primary sensory and lower areas, 279 00:17:51,230 --> 00:17:54,980 to association areas which get connections 280 00:17:54,980 --> 00:17:57,710 from those primary areas. 281 00:17:57,710 --> 00:18:00,590 You have then the modality-specific association 282 00:18:00,590 --> 00:18:03,730 areas and the multimodal areas. 283 00:18:03,730 --> 00:18:09,020 Those are the areas closely connected-- adjacent boxes here 284 00:18:09,020 --> 00:18:11,830 are interconnected, two-way connections 285 00:18:11,830 --> 00:18:13,600 between those areas. 286 00:18:13,600 --> 00:18:17,940 So for every one of these you could draw arrows like this, 287 00:18:17,940 --> 00:18:25,890 and sometimes when I show this I do show that kind of arrow. 288 00:18:25,890 --> 00:18:28,190 And then you have the paralimbic areas and then finally 289 00:18:28,190 --> 00:18:33,150 the limbic areas which are the other cortex 290 00:18:33,150 --> 00:18:39,510 and some subcortical regions, he calls corticoid 291 00:18:39,510 --> 00:18:42,050 because they have some layering. 292 00:18:42,050 --> 00:18:49,110 But I've drawn in there in red arrows direct connections 293 00:18:49,110 --> 00:18:51,896 or disynaptic connections to the hypothalamus. 294 00:18:54,580 --> 00:18:57,660 So, for example, we know the amygdala 295 00:18:57,660 --> 00:18:59,900 which is directly connected to the hypothalamus 296 00:18:59,900 --> 00:19:04,160 as well as through other areas of the limbic system, 297 00:19:04,160 --> 00:19:09,400 the amygdala gets direct input from association areas, 298 00:19:09,400 --> 00:19:14,930 multimodal especially, but even unimodal visual areas 299 00:19:14,930 --> 00:19:18,210 project onto the amygdala as discovered by Nauta. 300 00:19:22,130 --> 00:19:25,730 And then we also know that cingulate gyrus, 301 00:19:25,730 --> 00:19:29,770 parahippocampal areas, they project 302 00:19:29,770 --> 00:19:33,970 to hippocampus and to other of these limbic system 303 00:19:33,970 --> 00:19:35,960 structures which are all closely-- 304 00:19:35,960 --> 00:19:39,090 we know by definition, these are the areas closely connected 305 00:19:39,090 --> 00:19:41,760 to the hypothalamus. 306 00:19:41,760 --> 00:19:44,880 So let's focus mostly on the amygdala, 307 00:19:44,880 --> 00:19:48,220 and ask, what the heck is it? 308 00:19:48,220 --> 00:19:49,840 What does amygdala mean? 309 00:19:49,840 --> 00:19:51,766 Well it means almond. 310 00:19:51,766 --> 00:19:54,440 It's got an almond shape. 311 00:19:54,440 --> 00:19:55,350 Oh I shoot. 312 00:19:55,350 --> 00:19:59,302 I already deleted one of the other slides. 313 00:19:59,302 --> 00:20:03,130 I had a human brain there that shows-- 314 00:20:03,130 --> 00:20:05,850 I posted some slides somewhere online. 315 00:20:05,850 --> 00:20:06,910 I'll have to find them. 316 00:20:06,910 --> 00:20:09,490 You can see in a human dissection 317 00:20:09,490 --> 00:20:13,306 how apt a name that is for the amygdala. 318 00:20:17,570 --> 00:20:19,813 It's an almond-shaped structure that sits right 319 00:20:19,813 --> 00:20:25,560 in front of the anterior pole of the hippocampal formation which 320 00:20:25,560 --> 00:20:30,910 in a rodent would be the ventral pole. 321 00:20:30,910 --> 00:20:33,150 You can think of it as kind of a modified 322 00:20:33,150 --> 00:20:34,470 part of the corpus striatum. 323 00:20:34,470 --> 00:20:39,030 In fact, we call, in the classical anatomy literature, 324 00:20:39,030 --> 00:20:46,180 we call the basal ganglia the corpus striatum 325 00:20:46,180 --> 00:20:51,592 and we the amygdala, all called basal ganglia. 326 00:20:51,592 --> 00:20:54,630 Now actually, in embryological terms, 327 00:20:54,630 --> 00:20:58,310 only part of the amygdala is striatal in origin. 328 00:20:58,310 --> 00:21:01,090 Some of it's paleo in origin. 329 00:21:01,090 --> 00:21:04,920 In other words, it's like a cortex. 330 00:21:04,920 --> 00:21:08,370 But there's a very good reason-- some people have argued 331 00:21:08,370 --> 00:21:10,580 though they're actually separate structures. 332 00:21:10,580 --> 00:21:12,270 We should talk separately about them, 333 00:21:12,270 --> 00:21:15,660 but I would say no, because connections 334 00:21:15,660 --> 00:21:17,630 are what determines functions. 335 00:21:17,630 --> 00:21:20,140 And the connections of the amygdala 336 00:21:20,140 --> 00:21:22,820 indicate that it's one structure. 337 00:21:22,820 --> 00:21:25,850 They are closely connected, and they have common outputs. 338 00:21:29,240 --> 00:21:32,182 And as in the striatum, connections in the amygdala 339 00:21:32,182 --> 00:21:35,910 are [? elastic. ?] Remember I made a big deal out 340 00:21:35,910 --> 00:21:37,630 of that for striatum. 341 00:21:37,630 --> 00:21:42,040 It had originally olfactory heads were formed. 342 00:21:42,040 --> 00:21:47,210 It was the route through the ventral striatum, the oldest 343 00:21:47,210 --> 00:21:51,445 part of the striatum to influence movement which 344 00:21:51,445 --> 00:21:55,940 it did through the hypothalamus and midbrain. 345 00:21:55,940 --> 00:22:00,140 Well this part of the striatum is not 346 00:22:00,140 --> 00:22:02,940 concerned with the same kind of movements. 347 00:22:02,940 --> 00:22:08,120 It's concerned with motivation, emotion, feelings, 348 00:22:08,120 --> 00:22:11,790 if we talk subjectively about it. 349 00:22:11,790 --> 00:22:14,990 So associations are formed between perceive objects 350 00:22:14,990 --> 00:22:18,370 and sounds on the one hand and apex and autonomic changes 351 00:22:18,370 --> 00:22:20,520 in the other. 352 00:22:20,520 --> 00:22:26,670 It gives objects in the world valences or affected tags. 353 00:22:26,670 --> 00:22:29,006 In other words, you can hang tags on things. 354 00:22:29,006 --> 00:22:30,010 I like that. 355 00:22:30,010 --> 00:22:31,550 I don't like that. 356 00:22:31,550 --> 00:22:32,560 That makes me happy. 357 00:22:32,560 --> 00:22:35,280 That upsets me. 358 00:22:35,280 --> 00:22:38,815 But we'll all learn things or most of it. 359 00:22:38,815 --> 00:22:42,220 There's argument about some of them like fear of snakes. 360 00:22:42,220 --> 00:22:44,800 They might be at least partly inherited. 361 00:22:52,150 --> 00:22:54,885 This is the collection of structures 362 00:22:54,885 --> 00:22:57,430 that we lump together and call the amygdala 363 00:22:57,430 --> 00:23:00,530 in a ventral view of a rabbit brain which 364 00:23:00,530 --> 00:23:02,270 is very similar to rodent brains. 365 00:23:05,845 --> 00:23:07,220 The connections are all the same. 366 00:23:07,220 --> 00:23:10,250 So here's the olfactory bulb way up at the front, 367 00:23:10,250 --> 00:23:15,621 but behind the olfactory bulb starts the olfactory cortex. 368 00:23:15,621 --> 00:23:19,306 The first part of it we call the olfactory peduncle, 369 00:23:19,306 --> 00:23:21,180 because it's sorts of a little stem connected 370 00:23:21,180 --> 00:23:23,750 to the rest of it. 371 00:23:23,750 --> 00:23:27,100 And you'll see they have these very widely projecting axons. 372 00:23:27,100 --> 00:23:31,290 They're very widely branching axons of the olfactory system, 373 00:23:31,290 --> 00:23:34,790 and they go back to this broadened part 374 00:23:34,790 --> 00:23:41,550 of that cortex which is why it gets the name pyriform cortex-- 375 00:23:41,550 --> 00:23:46,790 it's P- Y- R, not P- I- R. It's not the [? piricortex ?] It's 376 00:23:46,790 --> 00:23:49,580 the pear-shaped cortex, because this 377 00:23:49,580 --> 00:23:59,030 is the pear shape like the Bosc pears you 378 00:23:59,030 --> 00:24:00,150 buy in the supermarket. 379 00:24:00,150 --> 00:24:03,740 That's the shape it is. 380 00:24:03,740 --> 00:24:07,990 And this little special part of the olfactory bulb 381 00:24:07,990 --> 00:24:09,730 the olfactory bulb projects directly 382 00:24:09,730 --> 00:24:11,540 to the cortical nucleus to the amydala. 383 00:24:11,540 --> 00:24:14,360 So that's in red here. 384 00:24:14,360 --> 00:24:18,310 And medial nucleus connects to it, 385 00:24:18,310 --> 00:24:21,310 also gets direct olfactory input. 386 00:24:21,310 --> 00:24:24,390 That part, the cortical and medial nuclei 387 00:24:24,390 --> 00:24:26,480 are often lumped together even though one of them 388 00:24:26,480 --> 00:24:28,239 is paleo in origin and one of them 389 00:24:28,239 --> 00:24:31,190 is striatal because of the similarity of connections 390 00:24:31,190 --> 00:24:34,760 and because they get, not only direct olfactory input, they 391 00:24:34,760 --> 00:24:38,460 also get some input from the brainstem from the taste 392 00:24:38,460 --> 00:24:44,555 system, directly from brainstems from the parabrachial nuclei, 393 00:24:44,555 --> 00:24:47,040 so you've got taste information. 394 00:24:47,040 --> 00:24:50,580 It also gets pain input from the brainstem. 395 00:24:53,930 --> 00:25:02,430 And the basal [INAUDIBLE] nuclei, they get input 396 00:25:02,430 --> 00:25:07,030 from sensory systems like the visual system. 397 00:25:07,030 --> 00:25:11,510 Some of it comes directly from the thalamas, 398 00:25:11,510 --> 00:25:13,210 especially in the auditory system 399 00:25:13,210 --> 00:25:17,260 but there are some visual pathways too, but even more, 400 00:25:17,260 --> 00:25:20,340 especially for the visual system from cortical areas. 401 00:25:23,010 --> 00:25:26,160 They also have projections to cortex, especially 402 00:25:26,160 --> 00:25:28,200 to the prefrontal area. 403 00:25:28,200 --> 00:25:30,720 So the prefrontal area recipricolly connected 404 00:25:30,720 --> 00:25:33,260 to this, but all of these nuclei are 405 00:25:33,260 --> 00:25:36,870 connected to the central nucleus and have some other connections 406 00:25:36,870 --> 00:25:38,320 with each other. 407 00:25:38,320 --> 00:25:42,980 That central nucleus which is a striatal structure, striatal 408 00:25:42,980 --> 00:25:47,875 in origin, it gets input from all these different structures 409 00:25:47,875 --> 00:25:51,490 and it connects directly to basal forebrain 410 00:25:51,490 --> 00:25:52,730 and hypothalamus. 411 00:25:52,730 --> 00:25:54,015 So we want to look at that. 412 00:25:56,660 --> 00:25:59,900 So here I've just shown paleo and striatal [? derivatives ?] 413 00:25:59,900 --> 00:26:01,350 separate. 414 00:26:01,350 --> 00:26:02,970 I don't think it's such a big deal, 415 00:26:02,970 --> 00:26:04,303 because [INAUDIBLE] connections. 416 00:26:06,770 --> 00:26:11,450 It's really difficult to separate them in that way. 417 00:26:11,450 --> 00:26:17,010 So let's describe the stria terminalis Its origins, 418 00:26:17,010 --> 00:26:19,930 I just stated, comes from, mainly, 419 00:26:19,930 --> 00:26:23,700 the central nucleus and the amygdala. 420 00:26:23,700 --> 00:26:26,170 And then it's course in its major connections, 421 00:26:26,170 --> 00:26:30,080 and you'll see that its course is very much like the fornix 422 00:26:30,080 --> 00:26:31,590 fibers from the hippocampus. 423 00:26:34,340 --> 00:26:37,170 It has to go around the internal capsule fibers. 424 00:26:42,380 --> 00:26:45,806 And by going directly to the amygdala, 425 00:26:45,806 --> 00:26:48,270 it pretty directly influences motivational states. 426 00:26:52,190 --> 00:26:54,200 I want to start talking about it, just 427 00:26:54,200 --> 00:26:58,330 by showing a section of the rat here. 428 00:26:58,330 --> 00:26:59,260 This is the amygdala. 429 00:26:59,260 --> 00:27:01,485 I put dotted lines around it. 430 00:27:05,230 --> 00:27:07,470 This is olfactory cortex out here. 431 00:27:07,470 --> 00:27:10,440 There's the rhinal fissure. 432 00:27:10,440 --> 00:27:12,260 We look in the hypothalamus. 433 00:27:12,260 --> 00:27:14,150 There's the fornix, and I pointed out 434 00:27:14,150 --> 00:27:18,020 the ventral medial nucleus, because this central nucleus, 435 00:27:18,020 --> 00:27:22,930 which is here, can you see my pointer here? 436 00:27:22,930 --> 00:27:28,415 This area projects directly to the cells, the neurons, 437 00:27:28,415 --> 00:27:31,500 of the ventral nucleus hypothalamus. 438 00:27:31,500 --> 00:27:34,460 And we want to follow those. 439 00:27:34,460 --> 00:27:36,500 Here's the stria terminalis. 440 00:27:36,500 --> 00:27:37,990 I've outlined it for you. 441 00:27:37,990 --> 00:27:41,086 And you'll say, well how do you know that? 442 00:27:41,086 --> 00:27:43,900 Well If you look carefully here, you 443 00:27:43,900 --> 00:27:46,820 will see-- you'd have to blow it up a bit 444 00:27:46,820 --> 00:27:49,300 I guess to really see it, but let's do that. 445 00:27:53,600 --> 00:27:56,670 These are neurons. 446 00:27:56,670 --> 00:28:01,080 These little cells are oligodendro cells. 447 00:28:07,460 --> 00:28:14,600 The basic dye will stain the region 448 00:28:14,600 --> 00:28:18,390 of the nucleus in the oligodondron sites, 449 00:28:18,390 --> 00:28:20,550 and you'll see these little tiny cells 450 00:28:20,550 --> 00:28:23,780 all lined up along the myelinated axons. 451 00:28:23,780 --> 00:28:28,090 You see them here too, but here they're going differently. 452 00:28:31,600 --> 00:28:35,710 These axons here are going like this 453 00:28:35,710 --> 00:28:38,860 and coming out of the thalamus or coming from cortex 454 00:28:38,860 --> 00:28:42,840 and going down like this into the cerebral peduncles. 455 00:28:46,470 --> 00:28:50,800 And this is the white matter of the cortex up here. 456 00:28:50,800 --> 00:28:54,675 So all these axons are connected there. 457 00:28:54,675 --> 00:28:57,040 We go right up here, and here they go. 458 00:29:01,540 --> 00:29:05,730 This is white matter of the cortex. 459 00:29:05,730 --> 00:29:14,740 So here then are the fibers that are-- 460 00:29:14,740 --> 00:29:22,890 you can see them here coming out of-- here they come here. 461 00:29:32,260 --> 00:29:35,805 So now I've just drawn a line around here. 462 00:29:35,805 --> 00:29:39,400 So why do you see two of them? 463 00:29:39,400 --> 00:29:43,080 Because these axons go around the caudal end 464 00:29:43,080 --> 00:29:44,920 of the internal capsule. 465 00:29:44,920 --> 00:29:45,830 They go around. 466 00:29:45,830 --> 00:29:48,040 They're the same axons you see here, 467 00:29:48,040 --> 00:29:49,700 you're seeing again up here. 468 00:29:49,700 --> 00:29:52,920 Just like if we were more caudal in the brain, 469 00:29:52,920 --> 00:29:55,670 we would see hippocampus going all the way down ventrally 470 00:29:55,670 --> 00:29:58,770 here, and with the axons coming out 471 00:29:58,770 --> 00:30:02,600 of that hippocampus are mostly collected 472 00:30:02,600 --> 00:30:04,100 in the fimbria of the fornix. 473 00:30:04,100 --> 00:30:07,890 And there's the fimbria of the fornix up here. 474 00:30:07,890 --> 00:30:11,010 And in this dorsal part of the hippocampus, 475 00:30:11,010 --> 00:30:13,210 the fornix fibers are there. 476 00:30:21,590 --> 00:30:24,350 So there's fimbria with the other fornix. 477 00:30:27,290 --> 00:30:29,840 And all those fibers are collected there. 478 00:30:29,840 --> 00:30:32,490 Where else do we see those axons in this section? 479 00:30:39,870 --> 00:30:43,690 Yet those axons go around the internal capsule too. 480 00:30:43,690 --> 00:30:46,470 But then where they go? 481 00:30:46,470 --> 00:30:49,090 They come down in from of the thalamus, 482 00:30:49,090 --> 00:30:51,790 they go into the septal area, but some of them 483 00:30:51,790 --> 00:30:52,766 go more caudally. 484 00:30:52,766 --> 00:30:53,640 Where are they going? 485 00:30:53,640 --> 00:30:56,494 This is Papez circuit. 486 00:30:56,494 --> 00:30:57,910 They're going to the hypothalamus. 487 00:30:57,910 --> 00:30:59,000 Where in the hypothalamus? 488 00:31:04,440 --> 00:31:07,900 I'm going to stop right here until one of you tells me. 489 00:31:07,900 --> 00:31:12,394 Where's the hippocampus project in the hypothalamus? 490 00:31:12,394 --> 00:31:13,185 It's Papez circuit. 491 00:31:13,185 --> 00:31:16,190 Come on. 492 00:31:16,190 --> 00:31:18,280 Mammillary bodies. 493 00:31:18,280 --> 00:31:20,750 And there's the fornix fibers. 494 00:31:26,900 --> 00:31:31,620 And then those fibers from the amygdala 495 00:31:31,620 --> 00:31:33,060 are doing something similar. 496 00:31:33,060 --> 00:31:35,030 Here they are. 497 00:31:35,030 --> 00:31:37,600 There they are. 498 00:31:37,600 --> 00:31:39,990 Where are those down here? 499 00:31:39,990 --> 00:31:46,590 They're here in that light area around-- because the dendrites 500 00:31:46,590 --> 00:31:50,120 of the cells in the ventromedial nucleus 501 00:31:50,120 --> 00:31:53,077 protrude out into that light area where 502 00:31:53,077 --> 00:31:54,160 you see the clumped cells. 503 00:31:56,970 --> 00:32:07,340 So the cells here in central nucleus 504 00:32:07,340 --> 00:32:11,190 go up, around the back of the internal capsule, 505 00:32:11,190 --> 00:32:16,090 then they follow around, come down 506 00:32:16,090 --> 00:32:19,930 through the basal forebrain, and run caudally just 507 00:32:19,930 --> 00:32:21,680 like the fornix. 508 00:32:21,680 --> 00:32:28,570 Here's our view of the-- medial view of the hemisphere where 509 00:32:28,570 --> 00:32:31,070 I've pretended it was transparent, 510 00:32:31,070 --> 00:32:33,250 so I can show you these structures. 511 00:32:33,250 --> 00:32:36,900 There's the amygdala right in front 512 00:32:36,900 --> 00:32:45,670 of the ventral end of the hippocampus in a rodent. 513 00:32:45,670 --> 00:32:47,280 There come those axons. 514 00:32:47,280 --> 00:32:49,470 They're going around the internal capsule 515 00:32:49,470 --> 00:32:51,890 which I've cut off here. 516 00:32:51,890 --> 00:32:53,840 I've cut them right there, but they're 517 00:32:53,840 --> 00:32:57,640 terminating in the bed nucleus stria terminalis 518 00:32:57,640 --> 00:33:00,402 By definition, that's why we name it the bed nucleus, 519 00:33:00,402 --> 00:33:03,010 the stria terminalis, because those cells are 520 00:33:03,010 --> 00:33:05,835 right among the axons of the stria terminalis 521 00:33:05,835 --> 00:33:07,501 and they're getting connections from it. 522 00:33:11,270 --> 00:33:17,060 And similarly, the hippocampal fibers-- you see there I 523 00:33:17,060 --> 00:33:24,152 left those in black-- the columns of the fornix 524 00:33:24,152 --> 00:33:26,065 are right there next to the stria terminalis. 525 00:33:28,590 --> 00:33:33,262 They go to mammillary bodies, runs from the stria 526 00:33:33,262 --> 00:33:37,690 terminalis, though mainly to the ventromedial hypothalamus. 527 00:33:37,690 --> 00:33:40,320 There are other connections in the hypothalamus too 528 00:33:40,320 --> 00:33:45,090 of both those bundles of axons, but the major termination 529 00:33:45,090 --> 00:33:48,215 are in the mammillary bodies in the ventromedial hypothalamus. 530 00:33:54,470 --> 00:33:56,700 So this whole area is basal forebrain. 531 00:33:56,700 --> 00:34:00,250 We'll talk a little more about that. 532 00:34:00,250 --> 00:34:04,140 In the frontal sections here, these 533 00:34:04,140 --> 00:34:07,709 are the levels through the embryonic brain 534 00:34:07,709 --> 00:34:13,139 and here we're in the mid thalamic region. 535 00:34:13,139 --> 00:34:16,489 There's the amygdala down in the temporal lobe. 536 00:34:16,489 --> 00:34:19,690 And there's the stria terminalis coming 537 00:34:19,690 --> 00:34:22,900 around the internal capsule. 538 00:34:22,900 --> 00:34:25,760 And there's the bed nucleus, the stria terminalis. 539 00:34:25,760 --> 00:34:29,460 I cut it here right at the rostral limit of the bed 540 00:34:29,460 --> 00:34:33,310 nucleus and the caudal limit of the nucleus accumbens. 541 00:34:33,310 --> 00:34:37,459 Nucleus accumbens has become very big in humans. 542 00:34:37,459 --> 00:34:41,570 It gets a lot of input from the amygdala and the hippocampus, 543 00:34:41,570 --> 00:34:45,654 especially the hippocampus and other limbic system structures. 544 00:34:48,520 --> 00:34:52,286 And if we go forward, we just see nucleus accumbens, 545 00:34:52,286 --> 00:34:57,070 the major nucleus of the basal forebrain. 546 00:34:57,070 --> 00:35:00,030 Accumbens means leaning, because it's 547 00:35:00,030 --> 00:35:02,930 leaning against the septal which is here. 548 00:35:09,210 --> 00:35:10,520 A couple more questions here. 549 00:35:10,520 --> 00:35:14,140 What sensory inputs come to the cortical and medial nucleus 550 00:35:14,140 --> 00:35:18,090 and the amygdala without passing through the neocortex? 551 00:35:18,090 --> 00:35:20,340 We know they're very ancient from comparative studies. 552 00:35:20,340 --> 00:35:24,520 We keep seeing it even in really ancient vertebrates, 553 00:35:24,520 --> 00:35:26,900 vertebrates that is, that are still living 554 00:35:26,900 --> 00:35:28,920 but are very similar to vertebrates 555 00:35:28,920 --> 00:35:32,602 that lives hundreds and thousands of years ago. 556 00:35:36,060 --> 00:35:39,640 OK olfactory is certainly one of them. 557 00:35:39,640 --> 00:35:41,010 What's another one you'd expect? 558 00:35:41,010 --> 00:35:45,770 What was really important in getting animals 559 00:35:45,770 --> 00:35:48,590 to do one thing rather than another, 560 00:35:48,590 --> 00:35:52,720 is a source of reward important in feeding? 561 00:35:52,720 --> 00:35:53,570 Taste. 562 00:35:53,570 --> 00:35:54,530 Yes. 563 00:35:54,530 --> 00:35:57,030 And there are taste inputs directed from the brainstem 564 00:35:57,030 --> 00:35:57,660 too. 565 00:35:57,660 --> 00:36:00,460 Olfaction and taste and the other one 566 00:36:00,460 --> 00:36:03,870 is pain-- all come in there. 567 00:36:03,870 --> 00:36:08,408 Those are the ancient inputs to the cortical and medial nuclei. 568 00:36:11,270 --> 00:36:14,135 And then the question for us is the lateral nucleus 569 00:36:14,135 --> 00:36:17,330 the amydala receives various sensory inputs too, 570 00:36:17,330 --> 00:36:22,920 but they come by way of neocortical associations 571 00:36:22,920 --> 00:36:26,850 and a few of them directly from the thalamus 572 00:36:26,850 --> 00:36:29,028 but not from more caudal brainstem structures. 573 00:36:34,890 --> 00:36:40,960 And I showed you in the diagrams before those-- 574 00:36:40,960 --> 00:36:43,800 you think most about the visual system ones, 575 00:36:43,800 --> 00:36:48,760 but we know auditory system ones and we will come back to that. 576 00:36:48,760 --> 00:36:53,400 So here's what I just said. 577 00:36:53,400 --> 00:37:00,040 I also pointed out that basal, particularly the basal nucleus, 578 00:37:00,040 --> 00:37:03,020 the lateral somewhat, reciprocally 579 00:37:03,020 --> 00:37:06,530 connected to prefrontal cortex. 580 00:37:06,530 --> 00:37:08,130 This is that picture when we talked 581 00:37:08,130 --> 00:37:11,330 about auditory system from experiments 582 00:37:11,330 --> 00:37:14,950 where they labeled the cells in the medial colliculus body, 583 00:37:14,950 --> 00:37:18,990 and they traced the axons not only to auditory cortex, there 584 00:37:18,990 --> 00:37:23,160 here in the opossum but in the opossum very heavily 585 00:37:23,160 --> 00:37:26,200 to that lateral nucleus in the amygdala. 586 00:37:26,200 --> 00:37:28,970 But it also occurs in the hedgehog, and the treeshrew 587 00:37:28,970 --> 00:37:31,646 and the rat and the mouse. 588 00:37:31,646 --> 00:37:35,755 Probably in us although the connection to neocortex 589 00:37:35,755 --> 00:37:41,000 in the primates is by far the most important. 590 00:37:41,000 --> 00:37:44,340 I want to show you again what medical school 591 00:37:44,340 --> 00:37:46,380 illustrations can look like. 592 00:37:46,380 --> 00:37:48,780 To make it a little easier, just so 593 00:37:48,780 --> 00:37:51,200 you understand what they're doing here. 594 00:37:51,200 --> 00:37:53,630 They're trying to show too much, and because of the way 595 00:37:53,630 --> 00:37:58,390 the human brain's developed it's very distorted. 596 00:37:58,390 --> 00:38:01,415 This kind of picture is a lot easier to understand. 597 00:38:05,900 --> 00:38:10,030 This is the human, and I've shown inputs 598 00:38:10,030 --> 00:38:13,800 by labeling the cells red. 599 00:38:13,800 --> 00:38:17,690 The outputs I've shown the cells in the amygdala with a green 600 00:38:17,690 --> 00:38:19,930 dot so you can see. 601 00:38:19,930 --> 00:38:23,840 But a lot harder to understand than the way I'm presenting it. 602 00:38:30,440 --> 00:38:35,810 Here I'm in a dissection-- a big slice 603 00:38:35,810 --> 00:38:38,590 so you can see the myelinated fibers really clearly. 604 00:38:42,680 --> 00:38:44,980 This is from a book, beautiful book, 605 00:38:44,980 --> 00:38:47,850 that shows-- I can bring it in class 606 00:38:47,850 --> 00:38:52,540 and let you go through it-- showing beautiful dissections, 607 00:38:52,540 --> 00:38:56,050 and then he also has some of these sections. 608 00:38:56,050 --> 00:38:59,620 There you see the amygdala. 609 00:38:59,620 --> 00:39:05,850 This has to be-- I'll ask you what level this cut. 610 00:39:05,850 --> 00:39:08,580 This is thalamus here, and there's mammillary bodies 611 00:39:08,580 --> 00:39:09,080 there. 612 00:39:12,030 --> 00:39:17,300 If it were a rodent, this would be caudal thalamus, 613 00:39:17,300 --> 00:39:23,410 but in human, the way it's arranged, 614 00:39:23,410 --> 00:39:26,800 you can't count on that. 615 00:39:26,800 --> 00:39:31,300 There's the putamen, the caudate nucleus, 616 00:39:31,300 --> 00:39:32,960 but there's that big amygdala. 617 00:39:32,960 --> 00:39:37,940 And you'll see it's a abutting the more anterior 618 00:39:37,940 --> 00:39:41,770 parts of the corpus striatum right there. 619 00:39:47,110 --> 00:39:50,660 That's all amygdala and if we went back just a little bit, 620 00:39:50,660 --> 00:39:55,670 then we'd be in hippocampus, because that's 621 00:39:55,670 --> 00:40:00,500 got to be the anterior most part of the temporal lobe here. 622 00:40:00,500 --> 00:40:03,780 See there's the [INAUDIBLE], so this is all temporal lobe 623 00:40:03,780 --> 00:40:05,520 down here. 624 00:40:05,520 --> 00:40:09,510 This is parietal lobe up here. 625 00:40:09,510 --> 00:40:11,630 Or if we're very far anterior, it 626 00:40:11,630 --> 00:40:13,093 might even be coronal cortex. 627 00:40:17,350 --> 00:40:22,250 Now some of the early functional information around the amygdala 628 00:40:22,250 --> 00:40:24,680 functions came from electrical stimulation, 629 00:40:24,680 --> 00:40:28,010 and it's been done a lot in monkeys, 630 00:40:28,010 --> 00:40:29,760 but it's also been done in humans 631 00:40:29,760 --> 00:40:31,740 during surgical procedures. 632 00:40:31,740 --> 00:40:36,590 So I've taken this from human studies. 633 00:40:36,590 --> 00:40:38,950 You stimulate the cortical medial area, 634 00:40:38,950 --> 00:40:42,340 you get oral kinds of things, salivation, 635 00:40:42,340 --> 00:40:45,770 smacking of the lips, licking, chewing, 636 00:40:45,770 --> 00:40:48,690 and inhibitional involuntary movements as well. 637 00:40:48,690 --> 00:40:51,980 You can also get elimination behavior. 638 00:40:51,980 --> 00:40:54,580 If you stimulate the basal lateral nuclei 639 00:40:54,580 --> 00:40:58,570 of the amygdala in a human you get arousal, 640 00:40:58,570 --> 00:41:04,430 attentiveness, sometimes you get fear or rage, 641 00:41:04,430 --> 00:41:07,720 or you get anxiety and another very strong emotions, 642 00:41:07,720 --> 00:41:09,560 and you also get effects on memory. 643 00:41:09,560 --> 00:41:13,090 The person will say, I've been here before, 644 00:41:13,090 --> 00:41:15,800 and of course he hasn't been here before, 645 00:41:15,800 --> 00:41:17,620 but it feels like he has. 646 00:41:17,620 --> 00:41:21,800 It's an experience that many of us have when we're growing up. 647 00:41:21,800 --> 00:41:24,550 It's called a deja vu experience. 648 00:41:24,550 --> 00:41:28,724 How many of you can recall having such experiences? 649 00:41:28,724 --> 00:41:30,140 You've been in a situation, you're 650 00:41:30,140 --> 00:41:31,440 sure you were there before, but you 651 00:41:31,440 --> 00:41:32,530 couldn't have been there before. 652 00:41:32,530 --> 00:41:33,029 You know? 653 00:41:33,029 --> 00:41:35,440 You're in a new place. 654 00:41:35,440 --> 00:41:38,000 Well we think it probably happens 655 00:41:38,000 --> 00:41:42,842 through a minor seizure. 656 00:41:42,842 --> 00:41:46,390 It doesn't mean anything's wrong. 657 00:41:46,390 --> 00:41:47,490 It doesn't. 658 00:41:47,490 --> 00:41:49,890 Because these cells in the limbic system 659 00:41:49,890 --> 00:41:53,220 are prone to getting overly excited. 660 00:41:59,530 --> 00:42:01,600 People with temporal epilepsy can 661 00:42:01,600 --> 00:42:05,250 have deja vu preceding an actual seizure. 662 00:42:05,250 --> 00:42:08,460 But most of us, it doesn't go that far. 663 00:42:08,460 --> 00:42:11,410 I kept having those until, I think I was 30 years old. 664 00:42:16,070 --> 00:42:20,800 In the research, negative emotions have been stressed. 665 00:42:20,800 --> 00:42:24,130 And when you hear talks about amygdala, 666 00:42:24,130 --> 00:42:27,450 it used to be they would only talk about learned fears. 667 00:42:30,050 --> 00:42:32,950 That's changing a bit now, and I know from the human literature 668 00:42:32,950 --> 00:42:36,750 that it had to change because, in fact, positive feelings, as 669 00:42:36,750 --> 00:42:39,200 well as negative, can be obtained 670 00:42:39,200 --> 00:42:41,665 from manipulating that area. 671 00:42:44,470 --> 00:42:50,100 If you take the amygdala out, there's not much on humans, 672 00:42:50,100 --> 00:42:54,330 but occasionally there are humans with amygdala lesions, 673 00:42:54,330 --> 00:42:56,760 generally not bilateral though. 674 00:42:56,760 --> 00:43:00,020 It has been done on both sides with monkeys. 675 00:43:00,020 --> 00:43:02,720 And the first thing you notice-- monkeys, 676 00:43:02,720 --> 00:43:07,590 rhesus monkeys are pretty wild. 677 00:43:07,590 --> 00:43:11,630 We were getting rhesus monkeys that were wild caught. 678 00:43:11,630 --> 00:43:13,580 Then they started using only the ones that 679 00:43:13,580 --> 00:43:17,600 are bred in captivity, but even the ones bred in captivity, 680 00:43:17,600 --> 00:43:24,100 they grow up in these groups and they are not tame monkeys. 681 00:43:24,100 --> 00:43:28,230 But after the amygdala lesions, they were remarkably tame. 682 00:43:28,230 --> 00:43:30,880 They lost their normal defensiveness 683 00:43:30,880 --> 00:43:32,825 and aggressiveness in social situations. 684 00:43:35,880 --> 00:43:41,400 But the monkeys in social groups become socially isolated, 685 00:43:41,400 --> 00:43:47,805 because they're not sensitive, the way they should be, 686 00:43:47,805 --> 00:43:50,530 to dominance relationships. 687 00:43:50,530 --> 00:43:55,220 So you now have this monkey who's not a dominant animal 688 00:43:55,220 --> 00:43:58,205 at all, or he wasn't before the amygdala lesion. 689 00:43:58,205 --> 00:44:01,640 He will walk right up to the dominant male 690 00:44:01,640 --> 00:44:04,540 and get clobbered by him. 691 00:44:04,540 --> 00:44:09,310 So they get injured, they become isolated 692 00:44:09,310 --> 00:44:13,270 just because they lose their normal fears, 693 00:44:13,270 --> 00:44:15,310 especially in response to visual inputs. 694 00:44:17,850 --> 00:44:20,440 They show loss of autonomic reactions 695 00:44:20,440 --> 00:44:22,550 that accompany fear and anxiety. 696 00:44:25,190 --> 00:44:29,390 Also, you see some other types of effects like altered dietary 697 00:44:29,390 --> 00:44:30,730 preferences. 698 00:44:30,730 --> 00:44:33,860 And in the animal work, this was true also, 699 00:44:33,860 --> 00:44:37,410 the cats get hypersexuality. 700 00:44:37,410 --> 00:44:39,180 There's a famous picture that used 701 00:44:39,180 --> 00:44:43,510 to be reproduced in all the physiological psychology 702 00:44:43,510 --> 00:44:49,000 or brain behavior books of a animal 703 00:44:49,000 --> 00:44:51,820 mounting another animal who's mounting another animal who's 704 00:44:51,820 --> 00:44:55,650 mounting another animal because they had amygdala issues. 705 00:44:59,140 --> 00:45:02,710 The amygdala, like the striatum is involved in habit learning, 706 00:45:02,710 --> 00:45:05,240 but what kind of habits are we talking about now? 707 00:45:08,006 --> 00:45:12,340 Well, I just described learned fears and other kinds 708 00:45:12,340 --> 00:45:18,190 of learned [? effects. ?] That can be considered a habit. 709 00:45:20,900 --> 00:45:24,720 Prejudices are learned. 710 00:45:24,720 --> 00:45:29,300 That is an emotional habit, something learned. 711 00:45:29,300 --> 00:45:34,470 It's a tag we put on certain things or even certain people. 712 00:45:38,190 --> 00:45:44,710 That depends on the amygdala and basal forebrain, particularly 713 00:45:44,710 --> 00:45:46,910 the amygdala because its close connections 714 00:45:46,910 --> 00:45:48,730 to the temporal lobe. 715 00:45:51,400 --> 00:45:55,290 This is from a study of fear conditioning 716 00:45:55,290 --> 00:45:59,770 that was found to be dependent on the amygdala in rats. 717 00:45:59,770 --> 00:46:06,350 So here you have a rat in a box with a grid they can electrify 718 00:46:06,350 --> 00:46:09,910 and there's a speaker here and they're sounding a tone. 719 00:46:09,910 --> 00:46:13,220 And you can see in response to the tone-- the left graph here 720 00:46:13,220 --> 00:46:15,820 is blood pressure, doesn't change very much. 721 00:46:15,820 --> 00:46:18,340 This is the time he spends resting 722 00:46:18,340 --> 00:46:23,730 his behavior, freezing behavior, very little. 723 00:46:23,730 --> 00:46:25,380 When the sound is [? novel, ?] you'll 724 00:46:25,380 --> 00:46:28,142 get a little bit of increase in blood pressure, a little bit 725 00:46:28,142 --> 00:46:29,600 of freezing right at the beginning, 726 00:46:29,600 --> 00:46:33,770 and then he gets used to it and you don't get in anymore. 727 00:46:33,770 --> 00:46:39,070 But now, when you get the sound, you electrify the grid, 728 00:46:39,070 --> 00:46:42,016 as you'd expect, blood pressure goes way up. 729 00:46:42,016 --> 00:46:44,975 He freezes a lot because he can't get away. 730 00:46:44,975 --> 00:46:47,630 Of course, he tries to run, but he can't get away. 731 00:46:50,590 --> 00:46:55,020 They don't shock them so much that they're really injured. 732 00:46:55,020 --> 00:47:01,750 It's not a super cruel experiment, 733 00:47:01,750 --> 00:47:04,420 and it's often been used to study fear condition. 734 00:47:04,420 --> 00:47:08,360 But anyway, after they learn that association, now you just 735 00:47:08,360 --> 00:47:12,180 give the sound, you don't electrify the grid. 736 00:47:12,180 --> 00:47:13,610 Blood pressure goes up. 737 00:47:13,610 --> 00:47:15,450 Freezing goes up. 738 00:47:15,450 --> 00:47:17,972 That's learned fear, and that's how it's measured. 739 00:47:22,460 --> 00:47:26,310 [? Ablation ?] amygdala or just damaged pathway 740 00:47:26,310 --> 00:47:29,720 from the medial [INAUDIBLE] body of the thalamus 741 00:47:29,720 --> 00:47:35,350 to the amygdala, you get rid of that. 742 00:47:35,350 --> 00:47:36,730 There's pretty good evidence that 743 00:47:36,730 --> 00:47:42,314 depends on that auditory pathway from the thalamus 744 00:47:42,314 --> 00:47:44,605 to the amygdala to the lateral nucleus to the amygdala. 745 00:47:48,162 --> 00:47:49,745 There's interesting lesion experiments 746 00:47:49,745 --> 00:47:51,036 that have been done in monkeys. 747 00:47:51,036 --> 00:47:54,970 I want to go through this quickly. 748 00:47:54,970 --> 00:47:59,440 How do you produce a monkey that shows all these bizarre effects 749 00:47:59,440 --> 00:48:02,560 of amygdala ablation only when he's looking with one eye 750 00:48:02,560 --> 00:48:04,423 but not when he's looking with the other. 751 00:48:04,423 --> 00:48:05,298 AUDIENCE: [INAUDIBLE] 752 00:48:07,874 --> 00:48:08,860 PROFESSOR: Louder. 753 00:48:08,860 --> 00:48:11,330 AUDIENCE: [INAUDIBLE] 754 00:48:11,330 --> 00:48:14,940 PROFESSOR: So you do a split brain operation meaning 755 00:48:14,940 --> 00:48:19,340 cut the commissures, cut the optic chiasm-- see, 756 00:48:19,340 --> 00:48:20,924 if you cut the optic chiasm, you still 757 00:48:20,924 --> 00:48:22,381 have ipsilateral fibers you haven't 758 00:48:22,381 --> 00:48:23,760 cut, the ones that don't cross. 759 00:48:26,800 --> 00:48:30,350 Like here, here's the chiasm, you cut around the midline. 760 00:48:30,350 --> 00:48:32,990 So now the right eye goes to the right side of the brain, 761 00:48:32,990 --> 00:48:34,480 the left eye goes to the left side. 762 00:48:34,480 --> 00:48:37,232 Of course, each eye sees only half the visual field. 763 00:48:42,180 --> 00:48:45,350 But to get this to work you start just 764 00:48:45,350 --> 00:48:50,570 with the amygdala lesion in one side, the left hemisphere. 765 00:48:50,570 --> 00:48:53,350 I'm looking at the top, but I'm showing where the amygdala is 766 00:48:53,350 --> 00:48:55,130 down below in the temporal lobe. 767 00:48:57,810 --> 00:49:01,530 So you have to not only cut the chiasm, 768 00:49:01,530 --> 00:49:05,760 you have to cut the commissures, because otherwise 769 00:49:05,760 --> 00:49:10,780 the visual input that reaches this visual cortex can 770 00:49:10,780 --> 00:49:14,240 go from the [? juxtastriat ?] areas here 771 00:49:14,240 --> 00:49:18,890 across to the other side, because these areas are 772 00:49:18,890 --> 00:49:20,265 interconnected across the chiasm. 773 00:49:25,390 --> 00:49:27,952 The reason they cut it all the way forward is they 774 00:49:27,952 --> 00:49:29,785 actually have to cut the interior commissure 775 00:49:29,785 --> 00:49:32,930 to get this to be complete, because the amygdala's 776 00:49:32,930 --> 00:49:35,110 connected to the amygdala area. 777 00:49:35,110 --> 00:49:37,700 Temporal lobe structures, even temporal unicortex 778 00:49:37,700 --> 00:49:41,260 is connected across the interior commissure too. 779 00:49:41,260 --> 00:49:45,580 So they cut these commissures and now the animal 780 00:49:45,580 --> 00:49:47,630 has a totally different personality 781 00:49:47,630 --> 00:49:49,672 with one eye than with the other. 782 00:49:52,800 --> 00:49:56,180 We call that a disconnection syndrome. 783 00:49:56,180 --> 00:49:58,620 Disconnection syndromes have become 784 00:49:58,620 --> 00:50:04,840 well known in human neurology, because many lesions, 785 00:50:04,840 --> 00:50:09,400 human strokes, can eliminate a particular group of axons, 786 00:50:09,400 --> 00:50:13,200 a particular pathway. 787 00:50:13,200 --> 00:50:18,330 So the person can lose his ability to read, for example, 788 00:50:18,330 --> 00:50:24,450 but he can see perfectly well and he can respond to objects, 789 00:50:24,450 --> 00:50:27,700 but if you've disconnected the pathway going 790 00:50:27,700 --> 00:50:34,000 to areas, the Wernicke's area of the temporal and posterior 791 00:50:34,000 --> 00:50:37,800 parietal cortex, then he won't be able to read. 792 00:50:41,760 --> 00:50:43,790 You can read the rest of this, and I describe it 793 00:50:43,790 --> 00:50:45,070 in the chapter. 794 00:50:45,070 --> 00:50:48,400 Learn about how aggression-- these are all associated 795 00:50:48,400 --> 00:50:51,160 with amygdala functions-- we know aggression 796 00:50:51,160 --> 00:50:57,690 is also highly dependant on amygdala 797 00:50:57,690 --> 00:51:00,440 even though it's also generated through the hypothalamus 798 00:51:00,440 --> 00:51:02,050 of course. 799 00:51:02,050 --> 00:51:05,710 The endbrain structure that's most closely connected to it, 800 00:51:05,710 --> 00:51:08,450 in fact, it's a major function of that connection 801 00:51:08,450 --> 00:51:10,480 from amygdala to the ventromedial hypothalamic 802 00:51:10,480 --> 00:51:12,090 nucleus. 803 00:51:12,090 --> 00:51:15,170 And you can stimulate the ventromedial nucleus 804 00:51:15,170 --> 00:51:18,250 hypothalamus and get aggressive behavior, 805 00:51:18,250 --> 00:51:20,920 but that is enhanced by testosterone. 806 00:51:20,920 --> 00:51:26,570 This is just an experiment that shows males, 807 00:51:26,570 --> 00:51:31,440 high aggressiveness-- it's low in females over here-- 808 00:51:31,440 --> 00:51:38,130 but if you castrate them, their aggressiveness goes down. 809 00:51:38,130 --> 00:51:40,770 This is studies of rats, but it's 810 00:51:40,770 --> 00:51:43,680 been done on a number of other species as well. 811 00:51:43,680 --> 00:51:50,135 Then you start administering the testosterone 812 00:51:50,135 --> 00:51:51,260 which affects the amygdala. 813 00:51:51,260 --> 00:51:55,390 Then aggressiveness comes back unless you 814 00:51:55,390 --> 00:51:59,620 drop the level of testosterone you're 815 00:51:59,620 --> 00:52:01,390 administering to low levels. 816 00:52:08,270 --> 00:52:11,220 Read about the basal forebrain. 817 00:52:11,220 --> 00:52:13,790 I think that we will have time to go through basal forebrain, 818 00:52:13,790 --> 00:52:16,860 and I want you to understand this hypothesis, 819 00:52:16,860 --> 00:52:20,885 because it relates to Chapter 13, studies of plasticity. 820 00:52:24,210 --> 00:52:28,380 | makes a prediction that has been verified indirectly 821 00:52:28,380 --> 00:52:33,195 in studies of humans after Hurley temporal lobe lesions 822 00:52:33,195 --> 00:52:36,300 in certain groups of schizophrenics. 823 00:52:36,300 --> 00:52:42,120 This is from one of my papers, a paper published in 1979 824 00:52:42,120 --> 00:52:42,620 I think. 825 00:52:46,440 --> 00:52:49,090 We'll come back to that next time.