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 00:00:23,490 --> 00:00:26,350 PROFESSOR: So, no quiz today and no quiz 9 00:00:26,350 --> 00:00:32,600 Friday, but I am posting a homework that will be due 10 00:00:32,600 --> 00:00:37,480 Friday, very late on Friday. 11 00:00:40,640 --> 00:00:46,920 We can't officially have them do after Friday, 12 00:00:46,920 --> 00:00:49,740 but I felt the homework would be more useful to you 13 00:00:49,740 --> 00:00:51,035 in getting ready for the final. 14 00:00:56,176 --> 00:00:58,020 I wrote eight questions. 15 00:00:58,020 --> 00:01:00,740 We want you to write on six of them at least. 16 00:01:00,740 --> 00:01:03,890 If you want to write on the extra ones, if you have time, 17 00:01:03,890 --> 00:01:04,510 that's fine. 18 00:01:04,510 --> 00:01:07,880 We'll give you extra credit for that. 19 00:01:07,880 --> 00:01:10,830 All right, now, from the last session, 20 00:01:10,830 --> 00:01:17,890 what we didn't finish was talking about-- 21 00:01:17,890 --> 00:01:24,080 we talked about stem cells put in the brain as a treatment 22 00:01:24,080 --> 00:01:25,590 for Parkinson's. 23 00:01:25,590 --> 00:01:30,530 And I want to talk about the cells that 24 00:01:30,530 --> 00:01:36,000 are being generated normally in the adult brain. 25 00:01:36,000 --> 00:01:39,990 This was first discovered here at MIT 26 00:01:39,990 --> 00:01:46,490 when Joseph Altman was in the department, before he took up 27 00:01:46,490 --> 00:01:49,680 a position at Purdue University where he's spent over sense. 28 00:01:53,190 --> 00:01:55,340 He discovered them in two places. 29 00:01:55,340 --> 00:01:58,630 We talked about one of those already, 30 00:01:58,630 --> 00:02:01,010 the new neurons that are generated 31 00:02:01,010 --> 00:02:03,640 in the olfactory bulb. 32 00:02:03,640 --> 00:02:06,270 But he also discovered that they were generated 33 00:02:06,270 --> 00:02:11,580 in adult rats in the hippocampus, 34 00:02:11,580 --> 00:02:14,600 specifically in the dentate gyrus, the granule cells 35 00:02:14,600 --> 00:02:17,630 of the dentate gyrus, similarly in the olfactory bulbs. 36 00:02:17,630 --> 00:02:20,030 They were the granule cells that have turnover, 37 00:02:20,030 --> 00:02:25,090 about a 40-day turnover in rats, and they 38 00:02:25,090 --> 00:02:27,540 migrate from the lateral ventricles 39 00:02:27,540 --> 00:02:30,750 to the olfactory bulbs and in the hippocampus. 40 00:02:30,750 --> 00:02:34,010 Similarly, they're generated in ventricular layer, 41 00:02:34,010 --> 00:02:38,615 and they migrate to the adult position, 42 00:02:38,615 --> 00:02:41,029 there's turnover of those cells. 43 00:02:41,029 --> 00:02:43,320 It's not that we're getting a bigger and bigger dentate 44 00:02:43,320 --> 00:02:46,107 gyrus, because we learned more and more, 45 00:02:46,107 --> 00:02:47,190 there's actually turnover. 46 00:02:53,010 --> 00:02:58,920 There are data obtained by some labs that indicate that there's 47 00:02:58,920 --> 00:03:05,540 a much lower level of generation of new cells in other places 48 00:03:05,540 --> 00:03:08,850 as well, including neocortex. 49 00:03:08,850 --> 00:03:11,010 But it's been a lot more controversial. 50 00:03:11,010 --> 00:03:13,140 When you're just looking at Nissl stains, 51 00:03:13,140 --> 00:03:22,380 it can be very difficult to discriminate some glial cells, 52 00:03:22,380 --> 00:03:24,285 some astrocytes from neurons. 53 00:03:27,170 --> 00:03:31,170 But with all the reports that have appeared 54 00:03:31,170 --> 00:03:33,410 and the studies that have been done, 55 00:03:33,410 --> 00:03:35,705 there are antibodies that allow them to discriminate, 56 00:03:35,705 --> 00:03:40,720 that there appears to be some new neurons generated 57 00:03:40,720 --> 00:03:42,730 in the adult brain. 58 00:03:42,730 --> 00:03:44,960 But we really don't know anything 59 00:03:44,960 --> 00:03:50,465 about them and their function, except in the hippocampus 60 00:03:50,465 --> 00:03:51,590 where they've been studied. 61 00:03:58,560 --> 00:04:00,630 These are just pictures to remind you 62 00:04:00,630 --> 00:04:04,060 about-- I noticed here, looking at these old Scientific 63 00:04:04,060 --> 00:04:07,691 American figures by Kemperman and Gage, 64 00:04:07,691 --> 00:04:09,440 where they were talking about the new cell 65 00:04:09,440 --> 00:04:12,660 generation in the hippocampus, they have this picture 66 00:04:12,660 --> 00:04:16,950 and they show this box here. 67 00:04:16,950 --> 00:04:19,420 And then, here's the blow-up. 68 00:04:19,420 --> 00:04:23,910 And the blow-up is from down here. 69 00:04:23,910 --> 00:04:26,460 Because, notice, down here the dendrites, 70 00:04:26,460 --> 00:04:28,910 the cells would be here and the dendrites 71 00:04:28,910 --> 00:04:32,070 would be going up like this. 72 00:04:32,070 --> 00:04:35,240 Well, there, the dendrites are going down. 73 00:04:35,240 --> 00:04:39,450 But these are the way those little cells and the dentate 74 00:04:39,450 --> 00:04:41,190 gyrus. 75 00:04:41,190 --> 00:04:43,200 This is a study I did put in the book 76 00:04:43,200 --> 00:04:47,310 because it gave a demonstration that these two cells are 77 00:04:47,310 --> 00:04:49,490 being generated in humans as well. 78 00:04:49,490 --> 00:04:56,810 These were people that were being treated for cancer, 79 00:04:56,810 --> 00:04:59,840 and in taking tissue from the cancer, 80 00:04:59,840 --> 00:05:04,030 they needed to know how much new cell generation was there. 81 00:05:04,030 --> 00:05:07,390 You know in a cancer there's abnormal proliferation 82 00:05:07,390 --> 00:05:09,230 of cells. 83 00:05:09,230 --> 00:05:13,560 So they give them bromodeoxyuridine, 84 00:05:13,560 --> 00:05:17,670 which labels the newly generated cells. 85 00:05:17,670 --> 00:05:23,860 So in patients who died, they were able to get some tissue. 86 00:05:23,860 --> 00:05:28,220 This is just an example of that, where they show up, 87 00:05:28,220 --> 00:05:31,500 BRDU-labeled granule cell, indicating 88 00:05:31,500 --> 00:05:36,425 that it was generated around the time that BRDU was injected. 89 00:05:39,750 --> 00:05:41,290 All right. 90 00:05:41,290 --> 00:05:46,180 Now, the studies of this cell generation in rats, 91 00:05:46,180 --> 00:05:48,260 they not only look at the cell generation, 92 00:05:48,260 --> 00:05:54,480 they look at it's rate and what conditions are affecting it. 93 00:05:54,480 --> 00:05:57,470 And this is from an earlier study 94 00:05:57,470 --> 00:06:00,692 where they had shown that if you enrich the environment-- 95 00:06:00,692 --> 00:06:02,025 this is an enriched environment. 96 00:06:05,050 --> 00:06:09,500 These-- are these mice or rats? 97 00:06:12,320 --> 00:06:14,810 Well, it happens in the both of them. 98 00:06:14,810 --> 00:06:16,000 I think these are rats. 99 00:06:16,000 --> 00:06:17,730 That shows they're small rats. 100 00:06:17,730 --> 00:06:23,070 And they show-- and all kinds of toys, a place to run around. 101 00:06:23,070 --> 00:06:25,140 They're changing these toys a lot 102 00:06:25,140 --> 00:06:27,460 so they keep some novelty there. 103 00:06:27,460 --> 00:06:30,690 So the rats are always exploring. 104 00:06:30,690 --> 00:06:33,340 And when they have an environment like that, 105 00:06:33,340 --> 00:06:37,770 instead of just putting the same number in a small plastic cage 106 00:06:37,770 --> 00:06:43,920 where there's not much to do, these animal 107 00:06:43,920 --> 00:06:48,290 show a lot more neurogenesis in the dentate gyrus. 108 00:06:48,290 --> 00:06:52,490 There's a picture showing different rate of neurogenesis. 109 00:06:52,490 --> 00:06:54,160 Now if you look online, you'll see 110 00:06:54,160 --> 00:06:55,800 that the more recent studies have 111 00:06:55,800 --> 00:06:58,060 extended this kind of work. 112 00:06:58,060 --> 00:07:06,360 They found that animals that are under a lot of stress-- I mean, 113 00:07:06,360 --> 00:07:09,346 if you give them learning to do, but it's very stressful 114 00:07:09,346 --> 00:07:10,720 and they're being shocked or this 115 00:07:10,720 --> 00:07:16,820 or that, animals under stress produce fewer new cells 116 00:07:16,820 --> 00:07:20,940 in the dentate gyrus so the cell turnover is 117 00:07:20,940 --> 00:07:24,320 much less or slower. 118 00:07:24,320 --> 00:07:26,350 Whereas, the happy animals, the animals that 119 00:07:26,350 --> 00:07:28,750 are getting reward, and it's not stressful, 120 00:07:28,750 --> 00:07:32,170 they are generating more cells. 121 00:07:32,170 --> 00:07:34,870 So people with-- these are fairly new findings, 122 00:07:34,870 --> 00:07:37,650 but it should apply to humans as well. 123 00:07:40,270 --> 00:07:43,110 It's a good incentive to get married and be happy 124 00:07:43,110 --> 00:07:45,740 because you'll be happier and you'll generate more. 125 00:07:45,740 --> 00:07:49,850 You'll remember things better. 126 00:07:49,850 --> 00:07:56,522 AUDIENCE: Is there any advantage for making less cells when 127 00:07:56,522 --> 00:07:57,326 [INAUDIBLE]? 128 00:07:57,326 --> 00:08:00,040 PROFESSOR: Yeah, what would be the function of that? 129 00:08:03,720 --> 00:08:05,850 It's a good question. 130 00:08:05,850 --> 00:08:07,460 That's what we have to think about. 131 00:08:07,460 --> 00:08:08,890 We need the research. 132 00:08:08,890 --> 00:08:10,690 But if you look online, you will see 133 00:08:10,690 --> 00:08:12,955 there is some recent work in this area. 134 00:08:17,680 --> 00:08:21,100 I suggest in the book that we know 135 00:08:21,100 --> 00:08:27,010 that young neurons in the brains with a lot of young neurons, 136 00:08:27,010 --> 00:08:30,630 in other words, that are developing animals 137 00:08:30,630 --> 00:08:34,350 and people, the amount of learning they do 138 00:08:34,350 --> 00:08:38,270 is much, much greater than in adults. 139 00:08:38,270 --> 00:08:40,230 Think of acquiring language. 140 00:08:40,230 --> 00:08:43,850 Kids are learning many new words every day. 141 00:08:43,850 --> 00:08:45,390 That's a lot of learning. 142 00:08:45,390 --> 00:08:47,380 They're learning many other things as well. 143 00:08:50,110 --> 00:08:54,580 So it just could be that young neurons are 144 00:08:54,580 --> 00:08:56,390 going to be more plastic, and the data 145 00:08:56,390 --> 00:08:58,170 indicate that that's true. 146 00:09:00,558 --> 00:09:01,474 AUDIENCE: [INAUDIBLE]? 147 00:09:06,210 --> 00:09:09,496 PROFESSOR: In stress, yes. 148 00:09:09,496 --> 00:09:10,412 AUDIENCE: [INAUDIBLE]? 149 00:09:18,279 --> 00:09:19,820 PROFESSOR: In other words, the growth 150 00:09:19,820 --> 00:09:23,024 itself is taking up energy, interesting. 151 00:09:23,024 --> 00:09:23,940 AUDIENCE: [INAUDIBLE]. 152 00:09:43,230 --> 00:09:46,200 PROFESSOR: Very good, this is in Ki Goosens' lab. 153 00:09:46,200 --> 00:09:51,080 They've been studying stress affects since she's come to MIT 154 00:09:51,080 --> 00:09:52,560 and joined the faculty here. 155 00:09:57,470 --> 00:09:59,940 I just want to show you briefly this experiment 156 00:09:59,940 --> 00:10:02,040 with implantation of stem cells. 157 00:10:02,040 --> 00:10:05,370 I thought I had done this last time, but it's here. 158 00:10:05,370 --> 00:10:07,700 This was an earlier work. 159 00:10:07,700 --> 00:10:10,550 And this has been going on and it started just a 160 00:10:10,550 --> 00:10:12,900 this little before this. 161 00:10:12,900 --> 00:10:15,120 But you will see this kind of work going on 162 00:10:15,120 --> 00:10:17,910 right up till the current year. 163 00:10:17,910 --> 00:10:21,180 There's a lot of it and a lot of competition in the area 164 00:10:21,180 --> 00:10:25,170 now to find sources of stem cells that 165 00:10:25,170 --> 00:10:28,780 can be used in treating human patients, 166 00:10:28,780 --> 00:10:33,800 including Parkinson's, but other things as well. 167 00:10:33,800 --> 00:10:38,020 This was an experiment just to prove that in rats you 168 00:10:38,020 --> 00:10:40,430 can get these cells to survive. 169 00:10:40,430 --> 00:10:45,150 So in this picture of a brain from the medial side 170 00:10:45,150 --> 00:10:48,070 that you've seen before, I show the level 171 00:10:48,070 --> 00:10:49,950 of a frontal section that goes right 172 00:10:49,950 --> 00:10:55,130 through the basal forebrain and septum, with some neocortex 173 00:10:55,130 --> 00:10:56,430 at the top. 174 00:10:56,430 --> 00:10:59,290 And here's the picture from the rat. 175 00:10:59,290 --> 00:11:01,590 And what they've done is they've injected 176 00:11:01,590 --> 00:11:07,950 a cannula that goes down like this. 177 00:11:07,950 --> 00:11:11,180 They're injecting into the basal forebrain here. 178 00:11:11,180 --> 00:11:12,950 Here's the septum area up here. 179 00:11:15,721 --> 00:11:18,220 These are the basal forebrain structures; olfactory tubercle 180 00:11:18,220 --> 00:11:19,490 there at the bottom. 181 00:11:19,490 --> 00:11:25,370 And they've taken the pictures of histological results 182 00:11:25,370 --> 00:11:28,460 where they made the section right through where 183 00:11:28,460 --> 00:11:31,360 the cannula went through the tissue. 184 00:11:31,360 --> 00:11:36,766 And as they put it in, some cells, of course, 185 00:11:36,766 --> 00:11:39,140 leaked out of the cannula, even though the main injection 186 00:11:39,140 --> 00:11:40,920 was down here in the basal forebrain. 187 00:11:40,920 --> 00:11:43,630 And there you see labeled cells. 188 00:11:43,630 --> 00:11:45,900 Four to nine months, they got results. 189 00:11:45,900 --> 00:11:48,560 Four to nine months after these were put in they 190 00:11:48,560 --> 00:11:52,760 got these results indicating that these cells are surviving 191 00:11:52,760 --> 00:11:56,280 over a long period of time. 192 00:11:56,280 --> 00:11:58,070 And in the area of the injection, 193 00:11:58,070 --> 00:12:03,860 you can see many living cells that 194 00:12:03,860 --> 00:12:05,380 weren't native to this brain. 195 00:12:05,380 --> 00:12:08,010 They were put in, so they know. 196 00:12:08,010 --> 00:12:09,760 But what do they become? 197 00:12:09,760 --> 00:12:12,390 Do we even though that they're neurons? 198 00:12:12,390 --> 00:12:17,580 And so, they tried staining for neurofilament protein, 199 00:12:17,580 --> 00:12:20,450 staining with glial fibrillary acidic protein 200 00:12:20,450 --> 00:12:23,610 to label astrocytes. 201 00:12:23,610 --> 00:12:29,070 And they saw that they got both astrocytes and neurons 202 00:12:29,070 --> 00:12:30,610 after these implantations. 203 00:12:30,610 --> 00:12:36,360 And then by looking at the other proteins, 204 00:12:36,360 --> 00:12:38,110 they showed that some of these cells 205 00:12:38,110 --> 00:12:43,720 are cholinergic, like the basal nucleus, medial septal cells. 206 00:12:43,720 --> 00:12:46,380 Various cells in the basal forebrain, 207 00:12:46,380 --> 00:12:49,710 from the basal nucleus on up into the septum, 208 00:12:49,710 --> 00:12:52,730 use acetylcholine as a transmitter and some 209 00:12:52,730 --> 00:12:56,090 of these stem cells are differentiating, 210 00:12:56,090 --> 00:12:58,820 not only acetylcholine cells. 211 00:12:58,820 --> 00:13:02,730 But they're picking up signals from the local environment that 212 00:13:02,730 --> 00:13:04,140 affects their differentiation. 213 00:13:04,140 --> 00:13:06,550 Remember, they're stem cells when they put them in, 214 00:13:06,550 --> 00:13:09,060 totally undifferentiated. 215 00:13:09,060 --> 00:13:15,000 And then they are maturing in the brain and differentiating. 216 00:13:15,000 --> 00:13:17,970 And here, I just mentioned that it's 217 00:13:17,970 --> 00:13:23,520 being done here at MIT in Rudy Jaenisch's lab. 218 00:13:23,520 --> 00:13:25,370 And he had various collaborators. 219 00:13:25,370 --> 00:13:30,170 And this is the reference to a paper 220 00:13:30,170 --> 00:13:33,270 they published in the proceedings of the National 221 00:13:33,270 --> 00:13:35,390 Academy of Sciences in 2008. 222 00:13:35,390 --> 00:13:40,600 And notice that it involved Martha Constantine-Paton 223 00:13:40,600 --> 00:13:46,700 in Jaenisch's lab and various people that 224 00:13:46,700 --> 00:13:48,550 helped with that research. 225 00:13:48,550 --> 00:13:52,090 And you'll see other publications in that year, 226 00:13:52,090 --> 00:13:55,150 and there's been a number since. 227 00:13:55,150 --> 00:14:01,460 Means of methodology for large scale generation 228 00:14:01,460 --> 00:14:04,355 dopamine producing cells that will differentiate 229 00:14:04,355 --> 00:14:10,900 into dopamine galecic cells from stem cells. 230 00:14:10,900 --> 00:14:15,160 They have various sources of these stem cells. 231 00:14:15,160 --> 00:14:17,750 Ideally, if you can get stem cells 232 00:14:17,750 --> 00:14:20,340 that you can generate from the patient themselves, 233 00:14:20,340 --> 00:14:24,350 it's the best. 234 00:14:24,350 --> 00:14:30,010 All right, let's talk about neocortex now 235 00:14:30,010 --> 00:14:33,570 for the rest of the class. 236 00:14:33,570 --> 00:14:35,540 In this first class, I just want to talk 237 00:14:35,540 --> 00:14:38,126 about evolution and functions of endbrain structures. 238 00:14:41,960 --> 00:14:44,851 So some of this will be reviewed, 239 00:14:44,851 --> 00:14:46,850 because I want to bring things together and make 240 00:14:46,850 --> 00:14:51,390 sure you're understand major points about the endbrain, 241 00:14:51,390 --> 00:14:55,366 a number which I've been talking about at various times 242 00:14:55,366 --> 00:14:56,950 in class. 243 00:14:56,950 --> 00:14:58,530 So in this first class, we'll talk 244 00:14:58,530 --> 00:15:00,880 about evolution and functions. 245 00:15:00,880 --> 00:15:04,570 And next time, we'll talk about cell types 246 00:15:04,570 --> 00:15:09,230 and how their connected, different regions 247 00:15:09,230 --> 00:15:11,820 of the neocortex, major fiber roots 248 00:15:11,820 --> 00:15:14,220 in and out of the endbrain. 249 00:15:14,220 --> 00:15:18,590 And then we'll talk about the thalamocortical system 250 00:15:18,590 --> 00:15:21,150 and about association cortex, where 251 00:15:21,150 --> 00:15:23,630 are they getting their thalamic input, 252 00:15:23,630 --> 00:15:25,980 the transcortical connections that 253 00:15:25,980 --> 00:15:29,012 interconnect these association areas. 254 00:15:29,012 --> 00:15:30,720 And I'll say a little bit about evolution 255 00:15:30,720 --> 00:15:34,920 of that thalamic structures. 256 00:15:34,920 --> 00:15:37,005 And then finally, this is the last chapter 257 00:15:37,005 --> 00:15:41,440 of the book, chapter 34, we'll talk, go back to development 258 00:15:41,440 --> 00:15:44,294 to talk specifically about neocortical development, 259 00:15:44,294 --> 00:15:45,960 because some of it is a little different 260 00:15:45,960 --> 00:15:50,095 from the spinal development that we focused on initially. 261 00:15:53,060 --> 00:15:58,520 We also talked a bit about development of the tectum, 262 00:15:58,520 --> 00:16:01,960 and then cortical plasticity, especially 263 00:16:01,960 --> 00:16:03,810 with an interest in adult plasticity 264 00:16:03,810 --> 00:16:07,240 and the structural changes that have been found. 265 00:16:07,240 --> 00:16:12,240 All right, so this is a picture we've seen a few times. 266 00:16:12,240 --> 00:16:17,650 It was one of the early studies using gene expression patterns 267 00:16:17,650 --> 00:16:22,030 to show how gene expression patterns for certain genes. 268 00:16:22,030 --> 00:16:24,425 Here, this is these two genes. 269 00:16:28,350 --> 00:16:31,870 It looks like I screwed this up. 270 00:16:31,870 --> 00:16:33,540 I didn't take the right one. 271 00:16:33,540 --> 00:16:35,720 Because what they actually did, as I remember, 272 00:16:35,720 --> 00:16:39,650 is EMX-1, and then the gene that's expressed 273 00:16:39,650 --> 00:16:41,070 in the green areas there. 274 00:16:43,362 --> 00:16:44,070 Sorry about that. 275 00:16:44,070 --> 00:16:45,410 It's correct in the book. 276 00:16:45,410 --> 00:16:48,000 I checked that and double checked it. 277 00:16:48,000 --> 00:16:50,900 But anyway, regardless, it always 278 00:16:50,900 --> 00:16:53,710 shows this kind of pattern, where 279 00:16:53,710 --> 00:17:01,645 you-- the cortex in mammals expresses EMX-1. 280 00:17:04,700 --> 00:17:09,079 The same gene is expressed in the frog in the dorsal cortex. 281 00:17:09,079 --> 00:17:12,300 And dorsal cortex there including 282 00:17:12,300 --> 00:17:16,450 the medial pallium, which become hippocampus. 283 00:17:16,450 --> 00:17:19,220 So that would be way over here in the mammal. 284 00:17:19,220 --> 00:17:24,420 And it also includes a large part of the olfactory cortex. 285 00:17:27,349 --> 00:17:29,150 And then, this is the striatal area, 286 00:17:29,150 --> 00:17:31,860 which expresses different genes. 287 00:17:31,860 --> 00:17:35,310 And these intermediate areas express other genes 288 00:17:35,310 --> 00:17:37,790 that they didn't study in this initial work, 289 00:17:37,790 --> 00:17:41,990 but that corresponds in the mammal 290 00:17:41,990 --> 00:17:46,415 mainly to the amygdala area in the claustrum, the amygdala 291 00:17:46,415 --> 00:17:46,950 region. 292 00:17:46,950 --> 00:17:49,620 And they find that gene is expressed 293 00:17:49,620 --> 00:17:51,380 in the dorsal ventricular ridge area 294 00:17:51,380 --> 00:17:54,720 of the reptiles and the birds. 295 00:17:54,720 --> 00:17:56,600 We don't call it dorsal ventricular ridge 296 00:17:56,600 --> 00:17:57,635 in the adult bird. 297 00:17:57,635 --> 00:18:03,520 We call it the nidopallium and subcomponents 298 00:18:03,520 --> 00:18:05,190 of the nidopallium. 299 00:18:05,190 --> 00:18:07,080 We keep calling it dorsal ventricular 300 00:18:07,080 --> 00:18:08,555 ridge in reptiles and turtles. 301 00:18:11,540 --> 00:18:14,570 You see it's there in frog also, but not 302 00:18:14,570 --> 00:18:17,380 in the same configuration. 303 00:18:17,380 --> 00:18:24,390 All right, so we think it's not just gene expression 304 00:18:24,390 --> 00:18:25,810 patterns that indicate this. 305 00:18:25,810 --> 00:18:29,780 We think the neocortex of mammals evolved 306 00:18:29,780 --> 00:18:34,510 from the that dorsal pallium or dorsal cortex 307 00:18:34,510 --> 00:18:37,910 of the ancestral vertebrates. 308 00:18:37,910 --> 00:18:41,130 And the dorsal cortex of amphibians and reptiles 309 00:18:41,130 --> 00:18:43,310 evolved from that same area. 310 00:18:43,310 --> 00:18:48,390 And the hyperpallium of birds evolved from that region 311 00:18:48,390 --> 00:18:51,190 in the birds. 312 00:18:51,190 --> 00:18:55,160 So we'll show pictures of that part of the hyperpallium 313 00:18:55,160 --> 00:18:56,720 we call the wulst. 314 00:18:56,720 --> 00:19:02,459 It can be compared to neocortex, quite specifically, 315 00:19:02,459 --> 00:19:03,625 in terms of its connections. 316 00:19:07,500 --> 00:19:15,480 And this refers to the amygdala, which 317 00:19:15,480 --> 00:19:18,310 now the gene expression data I should point out, 318 00:19:18,310 --> 00:19:22,130 is actually much more complex than this indicates. 319 00:19:22,130 --> 00:19:26,320 And there's been a lot of it, and there's multiple genes. 320 00:19:26,320 --> 00:19:29,670 And sometimes, the expression patterns 321 00:19:29,670 --> 00:19:34,020 don't lead to as clear cut a conclusion as others. 322 00:19:34,020 --> 00:19:38,460 So in the book, basing that kind of complexity, 323 00:19:38,460 --> 00:19:40,430 I do site that kind of data. 324 00:19:40,430 --> 00:19:45,960 But I've stressed function and connections 325 00:19:45,960 --> 00:19:48,360 because I know it's the connections that ultimately 326 00:19:48,360 --> 00:19:49,540 are determining behavior. 327 00:19:49,540 --> 00:19:53,919 It's not those gene expressions that determines the function. 328 00:19:53,919 --> 00:19:55,710 It's the, connections and what they become. 329 00:19:58,450 --> 00:20:01,360 And we'll see, the neocortex is actually made up. 330 00:20:01,360 --> 00:20:02,490 We've already seen that. 331 00:20:02,490 --> 00:20:07,430 You get contributions from various structures, 332 00:20:07,430 --> 00:20:11,880 not just that ventricular layer of the neocortex. 333 00:20:11,880 --> 00:20:15,550 They come from subcortical regions, too. 334 00:20:15,550 --> 00:20:18,680 And the same actually is true for these ventral structures 335 00:20:18,680 --> 00:20:23,820 like the amygdala and the anterior olfactory nucleus, 336 00:20:23,820 --> 00:20:25,770 which is part of the amygdala. 337 00:20:25,770 --> 00:20:30,340 Again, it's partly pallial, partly striatal. 338 00:20:30,340 --> 00:20:33,510 And the neocortex itself is like that. 339 00:20:33,510 --> 00:20:36,180 So that's one of the complexities we're faced with. 340 00:20:36,180 --> 00:20:39,080 So I looked at the amygdala and I 341 00:20:39,080 --> 00:20:42,800 study the connections, its inputs and its outputs, 342 00:20:42,800 --> 00:20:45,540 and its connections with itself, different components 343 00:20:45,540 --> 00:20:47,880 of the structure, and I see that it 344 00:20:47,880 --> 00:20:51,440 is a single structure in terms of function. 345 00:20:51,440 --> 00:20:53,870 So that's the approach I take because I'm 346 00:20:53,870 --> 00:20:57,940 interested in function primarily because I 347 00:20:57,940 --> 00:20:59,565 know that that's what drives evolution. 348 00:21:05,295 --> 00:21:07,145 It's the functional adaptations. 349 00:21:09,920 --> 00:21:14,270 So what sensory modality and what projections 350 00:21:14,270 --> 00:21:17,460 in that modality underlie the two major types 351 00:21:17,460 --> 00:21:20,920 of learning that I've been talking about in this class, 352 00:21:20,920 --> 00:21:24,590 so important in evolution of the forebrain? 353 00:21:24,590 --> 00:21:25,826 So what are those two types? 354 00:21:28,540 --> 00:21:32,170 And what are the structures in the center of? 355 00:21:32,170 --> 00:21:33,840 One of them? 356 00:21:33,840 --> 00:21:42,860 Sensory motor habits, the other spatial learning, 357 00:21:42,860 --> 00:21:45,525 knowledge place and the things in those places. 358 00:21:45,525 --> 00:21:48,270 So that's what we usually talk about when 359 00:21:48,270 --> 00:21:52,000 we talk about long term memory. 360 00:21:52,000 --> 00:21:54,640 But it is separate from habit formation, 361 00:21:54,640 --> 00:21:56,840 the striatal learning. 362 00:21:56,840 --> 00:21:59,600 So what was the modality? 363 00:21:59,600 --> 00:22:03,340 The initial one that dominated the endbrain, 364 00:22:03,340 --> 00:22:08,790 the primitive endbrain, which was olfaction. 365 00:22:08,790 --> 00:22:13,380 Olfaction initially totally dominated the endbrain. 366 00:22:13,380 --> 00:22:15,730 The endbrain is basically an outgrowth 367 00:22:15,730 --> 00:22:19,940 of the olfactory system, which developed up there 368 00:22:19,940 --> 00:22:23,450 in the rostral end of the brain in front 369 00:22:23,450 --> 00:22:29,210 of the primitive diencephalon. 370 00:22:29,210 --> 00:22:31,660 So these are the two kinds of learning. 371 00:22:31,660 --> 00:22:33,480 So we talk about object-- identification 372 00:22:33,480 --> 00:22:34,515 of objects and places. 373 00:22:37,720 --> 00:22:42,320 Very different kind of learning from the midbrain, 374 00:22:42,320 --> 00:22:45,470 because the midbrain, remember, when this was happening 375 00:22:45,470 --> 00:22:48,670 in the forebrain, animals already had this huge-- 376 00:22:48,670 --> 00:22:51,570 had a midbrain, a midbrain, that in some animals, 377 00:22:51,570 --> 00:22:52,890 became very, very large. 378 00:22:52,890 --> 00:22:56,937 Remember, the predatory fish, the enormous optic tectum 379 00:22:56,937 --> 00:22:57,770 and little endbrain. 380 00:23:01,620 --> 00:23:04,860 But what kind of learning goes on the midbrain? 381 00:23:04,860 --> 00:23:06,240 Not these kinds of learning. 382 00:23:06,240 --> 00:23:10,180 You don't have reinforcement learning and habit formation. 383 00:23:10,180 --> 00:23:14,040 You don't have a long term memory for places. 384 00:23:14,040 --> 00:23:18,550 What you have is innate recognition, 385 00:23:18,550 --> 00:23:21,200 triggering of innate responses. 386 00:23:21,200 --> 00:23:22,980 Think of the frog and his feeding. 387 00:23:25,720 --> 00:23:28,460 So we talk about-- I think ethologists give the best 388 00:23:28,460 --> 00:23:29,960 descriptions of that behavior, when 389 00:23:29,960 --> 00:23:35,790 we talk about visually elicited fixed action patterns, where 390 00:23:35,790 --> 00:23:37,990 the key stimuli for eliciting them 391 00:23:37,990 --> 00:23:46,320 are visual, many of them dealing with optic tectum. 392 00:23:46,320 --> 00:23:49,226 The plasticity is just sensitization and habituation 393 00:23:49,226 --> 00:23:51,150 in the tectum. 394 00:23:51,150 --> 00:23:54,715 But in the endbrain, you've got a lot more than just olfaction. 395 00:23:54,715 --> 00:23:56,775 You have these new forms of plasticity, 396 00:23:56,775 --> 00:24:00,486 the two types I just mentioned. 397 00:24:00,486 --> 00:24:03,320 And I just spell that out. 398 00:24:03,320 --> 00:24:04,710 You can read any of this. 399 00:24:04,710 --> 00:24:06,510 And here, I just spell out some details 400 00:24:06,510 --> 00:24:09,970 about the ancient inputs to the object learning 401 00:24:09,970 --> 00:24:14,227 system and the original outputs. 402 00:24:14,227 --> 00:24:15,810 They're very much like the connections 403 00:24:15,810 --> 00:24:18,663 to the amygdala and ventral striatum 404 00:24:18,663 --> 00:24:20,940 we've already gone over. 405 00:24:20,940 --> 00:24:24,100 And then, the learning, place learning, 406 00:24:24,100 --> 00:24:27,460 allowed anticipation of odors reaching the nostrils, 407 00:24:27,460 --> 00:24:29,870 and the possible act they could anticipate, 408 00:24:29,870 --> 00:24:34,050 the actions needed, again, evolved 409 00:24:34,050 --> 00:24:37,690 largely out of the olfactory system. 410 00:24:37,690 --> 00:24:40,019 And of course, later, the non-olfactory inputs 411 00:24:40,019 --> 00:24:41,310 became more and more important. 412 00:24:41,310 --> 00:24:45,840 And certainly, in the primates they become dominant. 413 00:24:45,840 --> 00:24:48,390 In most primates, though in some primates 414 00:24:48,390 --> 00:24:50,130 olfaction is still very important. 415 00:24:52,680 --> 00:24:56,770 And we know that the medial pallium 416 00:24:56,770 --> 00:25:02,230 is the most critical structure, important for those functions 417 00:25:02,230 --> 00:25:04,246 that evolved in the hippocampal formation. 418 00:25:11,430 --> 00:25:13,140 So then I talk about that invasion 419 00:25:13,140 --> 00:25:15,710 of non-olfactory inputs. 420 00:25:15,710 --> 00:25:18,350 You can read through this just to remind yourself 421 00:25:18,350 --> 00:25:20,760 of that when you read these slides. 422 00:25:20,760 --> 00:25:28,090 And what that did-- this is the questions I put in. 423 00:25:28,090 --> 00:25:31,100 So from what part of the primitive pallium 424 00:25:31,100 --> 00:25:35,150 in pre-mammalian reptiles did the neocortex evolve? 425 00:25:35,150 --> 00:25:39,320 What do I say earlier in the class? 426 00:25:39,320 --> 00:25:40,320 What is it called? 427 00:25:42,960 --> 00:25:45,225 Dorsal pallium or dorsal cortex. 428 00:25:53,820 --> 00:25:55,850 What part of the mammalian cortex 429 00:25:55,850 --> 00:25:58,740 does this pallial region in modern reptiles 430 00:25:58,740 --> 00:26:00,445 most closely resemble? 431 00:26:00,445 --> 00:26:03,020 Well, how do you study that? 432 00:26:03,020 --> 00:26:04,270 Look at connections. 433 00:26:04,270 --> 00:26:07,480 So when I asked this question, I was 434 00:26:07,480 --> 00:26:10,230 surprised that anatomy books never do that. 435 00:26:10,230 --> 00:26:16,460 I just loved to see studies of dorsal cortex in reptiles, 436 00:26:16,460 --> 00:26:18,340 and I found some. 437 00:26:18,340 --> 00:26:20,360 And I looked at the projections. 438 00:26:20,360 --> 00:26:23,810 They're all light connections of parahippocampal areas 439 00:26:23,810 --> 00:26:25,870 in the mammal. 440 00:26:25,870 --> 00:26:28,890 They're not connections like neocortex at all. 441 00:26:28,890 --> 00:26:33,100 Although, there are connections from non-olfactory modalities 442 00:26:33,100 --> 00:26:34,650 come in there. 443 00:26:34,650 --> 00:26:37,050 Part of it does get direct olfactory input, 444 00:26:37,050 --> 00:26:39,000 but much of it doesn't. 445 00:26:39,000 --> 00:26:41,310 Most of it's multi-modal, but sometimes you even 446 00:26:41,310 --> 00:26:43,860 have uni-modal areas developing. 447 00:26:43,860 --> 00:26:47,390 But the outputs are going into the medial pallium, which 448 00:26:47,390 --> 00:26:54,140 is the major, thickest part of the pallium in these animals. 449 00:26:54,140 --> 00:26:56,463 Remember that very thick medial pallium of the frog, 450 00:26:56,463 --> 00:26:56,963 for example. 451 00:26:59,850 --> 00:27:03,940 And yet, that area is-- that dorsal cortex 452 00:27:03,940 --> 00:27:08,160 is the part that changed in the mammals 453 00:27:08,160 --> 00:27:11,150 as the neocortex evolved. 454 00:27:11,150 --> 00:27:13,480 And what structure in the bird endbrain 455 00:27:13,480 --> 00:27:16,566 evolved in a way that resembles the way neocortex evolved 456 00:27:16,566 --> 00:27:17,065 in mammals? 457 00:27:21,140 --> 00:27:24,660 It's got a couple of different names. 458 00:27:24,660 --> 00:27:25,545 Any of you remember? 459 00:27:29,240 --> 00:27:31,730 The wulst is one name we use for it, 460 00:27:31,730 --> 00:27:35,710 and I'll show pictures of that. 461 00:27:35,710 --> 00:27:38,590 We also call it the hyperpallium. 462 00:27:38,590 --> 00:27:42,860 Now they call all those structures pallial, probably 463 00:27:42,860 --> 00:27:45,410 because of their homologies with mammals 464 00:27:45,410 --> 00:27:50,590 and also because of how they develop in the embryo. 465 00:27:50,590 --> 00:27:51,935 They are originally pallial. 466 00:28:02,200 --> 00:28:04,950 So this is just about what I just said. 467 00:28:04,950 --> 00:28:09,430 So why did mammals evolve a neocortex and birds 468 00:28:09,430 --> 00:28:12,480 evolve a wuslt? 469 00:28:12,480 --> 00:28:14,375 You know, it's a very good question 470 00:28:14,375 --> 00:28:18,210 that Altman takes up in his little book. 471 00:28:18,210 --> 00:28:23,750 He describes the avian wulst as much more efficient. 472 00:28:23,750 --> 00:28:27,510 What does he mean by that? 473 00:28:27,510 --> 00:28:32,060 This is a picture where I show the structures when 474 00:28:32,060 --> 00:28:33,740 we talked about the visual system. 475 00:28:33,740 --> 00:28:37,040 I'm showing the geniculate pathway carrying 476 00:28:37,040 --> 00:28:41,430 visual information to neocortex, and a pathway 477 00:28:41,430 --> 00:28:44,620 through the tectum, the superior colliculus. 478 00:28:44,620 --> 00:28:47,840 It goes to the lateral thalamus, a part of the pulvinar. 479 00:28:50,720 --> 00:28:54,640 Usually, we call it LP in the lab animal, the little animals 480 00:28:54,640 --> 00:28:58,490 we use, the rats, hamsters, and mice. 481 00:28:58,490 --> 00:29:02,730 And it projects primarily to the extrastriate visual areas. 482 00:29:02,730 --> 00:29:06,400 By primarily, I mean where the densest projections are. 483 00:29:06,400 --> 00:29:08,790 They do project more broadly as well, 484 00:29:08,790 --> 00:29:11,030 but these are the main projections. 485 00:29:11,030 --> 00:29:13,790 But if you look at reptiles and birds, 486 00:29:13,790 --> 00:29:17,190 they also contains these two pathways, 487 00:29:17,190 --> 00:29:22,270 one homologous to the geniculostriate system. 488 00:29:22,270 --> 00:29:26,485 And that one goes to this dorsal lateral cortex in reptiles. 489 00:29:29,050 --> 00:29:36,130 And it goes to the wulst, the hyperpallial area in the birds. 490 00:29:36,130 --> 00:29:42,520 And in very visual birds that have a large endbrain 491 00:29:42,520 --> 00:29:46,900 like the owl, the wulst is quite large. 492 00:29:46,900 --> 00:29:51,810 And, it's in fact, much thicker than the neocortex here. 493 00:29:51,810 --> 00:29:55,440 This other pathway doesn't go to the wulst. 494 00:29:55,440 --> 00:29:57,640 The other pathway here in reptiles 495 00:29:57,640 --> 00:29:59,470 goes to that dorsal ventricular ridge 496 00:29:59,470 --> 00:30:01,410 area that stays subcortical. 497 00:30:01,410 --> 00:30:04,250 So it's a subcortical structure. 498 00:30:04,250 --> 00:30:09,480 But it's not-- it used to be called striatum or neostriatum, 499 00:30:09,480 --> 00:30:11,460 but we don't call it that anymore 500 00:30:11,460 --> 00:30:15,250 because it's not homologous in its connections 501 00:30:15,250 --> 00:30:19,110 or its development to the striatum. 502 00:30:19,110 --> 00:30:24,210 And that's been supported by those gene expression studies. 503 00:30:24,210 --> 00:30:25,820 The striatum is down here. 504 00:30:25,820 --> 00:30:28,660 The stratum is down here in birds. 505 00:30:28,660 --> 00:30:34,130 But this whole area in between the real striatum and the wulst 506 00:30:34,130 --> 00:30:37,760 is called the nested pallium, or the nidopallium. 507 00:30:37,760 --> 00:30:40,715 We subdivided the part that gives the visual projection 508 00:30:40,715 --> 00:30:46,750 here from the tectum to nucleus rotundus, which 509 00:30:46,750 --> 00:30:48,720 is much larger than this area that 510 00:30:48,720 --> 00:30:51,180 gets direct input from the retina. 511 00:30:51,180 --> 00:30:53,440 It goes to this area called the entopallium. 512 00:30:56,095 --> 00:30:58,270 That was one of the discoveries made here 513 00:30:58,270 --> 00:31:02,100 at MIT by Harvey Karten, who I've 514 00:31:02,100 --> 00:31:04,300 been in touch with recently by the way. 515 00:31:04,300 --> 00:31:10,350 He's interacting with me a bit about the book. 516 00:31:10,350 --> 00:31:14,560 I send him a copy of it because he's 517 00:31:14,560 --> 00:31:18,980 been such an important player in this field, 518 00:31:18,980 --> 00:31:23,690 and he's still quite active in the San Diego area. 519 00:31:23,690 --> 00:31:25,360 He's in La Jolla. 520 00:31:25,360 --> 00:31:29,440 So this is Altman's simplified picture 521 00:31:29,440 --> 00:31:35,750 of neocortex and that much thicker wulst area. 522 00:31:35,750 --> 00:31:36,980 wulst means bulge. 523 00:31:36,980 --> 00:31:39,210 And you can see how in this section 524 00:31:39,210 --> 00:31:44,895 how it bulges out from the rest of the endbrain in the owl. 525 00:31:48,560 --> 00:31:56,560 It's a little bit-- we picked an owl and an owl monkey, 526 00:31:56,560 --> 00:32:01,830 but any monkey would do to make such a comparison. 527 00:32:01,830 --> 00:32:06,110 But we're going to talk about this simple lamination 528 00:32:06,110 --> 00:32:07,520 of the neocortex. 529 00:32:07,520 --> 00:32:12,550 The wulst lamination is much-- there are many more layers, 530 00:32:12,550 --> 00:32:14,080 and the cells are different. 531 00:32:14,080 --> 00:32:17,330 We have the pyramidal cell in cortex. 532 00:32:17,330 --> 00:32:21,910 These neurons in the wulst are generally stellate in shape. 533 00:32:24,540 --> 00:32:27,280 So to get the same processing power 534 00:32:27,280 --> 00:32:30,020 that you have in the wulst, mammals 535 00:32:30,020 --> 00:32:34,810 have evolved multiple visual areas that are interconnected. 536 00:32:34,810 --> 00:32:39,170 It seems to work extremely well, but with two disadvantages. 537 00:32:39,170 --> 00:32:43,100 You've got a lot more axon. 538 00:32:43,100 --> 00:32:47,050 Here the axons are shorter, interconnecting 539 00:32:47,050 --> 00:32:50,615 the different parts of the wulst because it's 540 00:32:50,615 --> 00:32:52,180 a thicker structure. 541 00:32:59,750 --> 00:33:02,820 So we have to ask, well, what are the advantages? 542 00:33:02,820 --> 00:33:04,680 Just look at neocortex first. 543 00:33:04,680 --> 00:33:08,340 This is a well known type of illustration, 544 00:33:08,340 --> 00:33:13,270 illustrating cortex in three different histological stains. 545 00:33:13,270 --> 00:33:15,135 At the far right is a Nissl stain, 546 00:33:15,135 --> 00:33:17,510 where you see the shape of the cell body 547 00:33:17,510 --> 00:33:20,860 and the density of the cells and their size 548 00:33:20,860 --> 00:33:24,350 in the different layers, which are numbered here. 549 00:33:24,350 --> 00:33:27,960 Layer one is always a layer of very few cells at the top. 550 00:33:27,960 --> 00:33:30,710 And you see here on the Golgi picture 551 00:33:30,710 --> 00:33:34,930 that that's mainly a layer of dendrites and axons. 552 00:33:34,930 --> 00:33:37,800 Here in an axon stain, you see that. 553 00:33:37,800 --> 00:33:41,320 A lot of axons, including many transversely running axons 554 00:33:41,320 --> 00:33:42,700 in layer one. 555 00:33:42,700 --> 00:33:46,780 And layer two and three are the smaller pyramidal cells 556 00:33:46,780 --> 00:33:48,740 of cortex. 557 00:33:48,740 --> 00:33:51,300 And you see them here in the Nissl, 558 00:33:51,300 --> 00:33:53,090 where the really big pyramidal cells are 559 00:33:53,090 --> 00:33:54,257 down here in layer five. 560 00:33:54,257 --> 00:33:56,340 And that's where you find the cells that give rise 561 00:33:56,340 --> 00:33:58,940 to the long outputs to subcortical regions. 562 00:34:02,280 --> 00:34:05,410 Some of the pyramidal cells in layer three or three B 563 00:34:05,410 --> 00:34:07,470 here are pretty large also. 564 00:34:07,470 --> 00:34:11,210 They're the ones with long transcortical connections. 565 00:34:11,210 --> 00:34:15,270 And then in layer four, this varies a little bit 566 00:34:15,270 --> 00:34:20,120 with the species and the stain you're using. 567 00:34:20,120 --> 00:34:22,739 You can see here, int good Nissl stain 568 00:34:22,739 --> 00:34:25,739 they're always small cells. 569 00:34:25,739 --> 00:34:27,510 And if we look in the Golgi, we see 570 00:34:27,510 --> 00:34:29,624 that there are these stellate cells that 571 00:34:29,624 --> 00:34:32,110 are generally not pyramidal cells. 572 00:34:32,110 --> 00:34:33,960 And there are other non-pyramidal cells 573 00:34:33,960 --> 00:34:37,110 scattered through the cortex. 574 00:34:37,110 --> 00:34:42,820 Here in the fiber stain, you see a couple of additional things. 575 00:34:42,820 --> 00:34:44,870 For one thing, you see that there's 576 00:34:44,870 --> 00:34:47,770 more than just six layers. 577 00:34:47,770 --> 00:34:49,310 Even in the Nissl stain it would be 578 00:34:49,310 --> 00:34:51,449 easy to name more than six layers. 579 00:34:51,449 --> 00:34:55,414 Layer six is always going to be divided into usually 580 00:34:55,414 --> 00:34:56,330 at least three layers. 581 00:34:59,200 --> 00:35:03,750 But to make sense out of all cortex 582 00:35:03,750 --> 00:35:09,550 and using the same kind of terms, we name just six layers, 583 00:35:09,550 --> 00:35:12,790 and then we talk about sublamination. 584 00:35:12,790 --> 00:35:15,910 Fiber stain show some additional layers 585 00:35:15,910 --> 00:35:19,830 because of these layers of transverse fibers. 586 00:35:19,830 --> 00:35:27,400 And then we see these fibers that travel perpendicular 587 00:35:27,400 --> 00:35:31,980 to the surface of the cortex that divide the cortex up 588 00:35:31,980 --> 00:35:33,890 into these different columns. 589 00:35:37,330 --> 00:35:41,260 And we want to know what those axons are. 590 00:35:41,260 --> 00:35:42,970 What are the transverse fibers? 591 00:35:42,970 --> 00:35:47,830 What are these vertically travelling fibers? 592 00:35:47,830 --> 00:35:51,420 And this is just a more-- just look at the Golgi stain. 593 00:35:51,420 --> 00:35:57,330 I took one here from Poliakov, a great Russian anatomist, 594 00:35:57,330 --> 00:35:59,460 and some of his pictures of the cortex which 595 00:35:59,460 --> 00:36:02,220 are quite elaborate and nice, and we 596 00:36:02,220 --> 00:36:04,404 see more of the cell types here. 597 00:36:04,404 --> 00:36:05,820 You see some of the stellate cells 598 00:36:05,820 --> 00:36:11,300 in very dense, dendritic arbors and axonal arbors. 599 00:36:11,300 --> 00:36:15,690 You'll see some of them are-- well, you'll see in the book 600 00:36:15,690 --> 00:36:20,110 that there's a picture there showing different cell 601 00:36:20,110 --> 00:36:22,440 types in the cortex. 602 00:36:22,440 --> 00:36:24,820 It's actually in chapter 33, which 603 00:36:24,820 --> 00:36:26,050 you may not have looked at. 604 00:36:26,050 --> 00:36:28,730 But the first two pictures in chapter 33 605 00:36:28,730 --> 00:36:31,980 show some interesting things about these cell 606 00:36:31,980 --> 00:36:33,000 types in the cortex. 607 00:36:38,700 --> 00:36:44,850 33-1 one shows two major types of cells, the excitatory 608 00:36:44,850 --> 00:36:48,660 glutamatergic cells, and then the other type 609 00:36:48,660 --> 00:36:50,770 are all inhibitory. 610 00:36:50,770 --> 00:36:53,800 Also, the first type is spiny. 611 00:36:53,800 --> 00:36:55,610 The second is non-spiny. 612 00:36:55,610 --> 00:36:58,790 So they're different in their morphology. 613 00:36:58,790 --> 00:37:03,260 Both groups include some stellate cells, but especially 614 00:37:03,260 --> 00:37:08,140 the cells using GABA, the inhibitory interneurons. 615 00:37:08,140 --> 00:37:12,500 In the Golgi stain you can't see which of these-- most of these 616 00:37:12,500 --> 00:37:15,830 are, in fact, inhibitory interneurons. 617 00:37:15,830 --> 00:37:19,880 The main excitatory interneurons are the neurons in layer four. 618 00:37:26,460 --> 00:37:29,240 In this chapter and in this particular question 619 00:37:29,240 --> 00:37:33,930 I'm asking for descriptions of different types of axon 620 00:37:33,930 --> 00:37:39,290 projections, axons that start in the cortex 621 00:37:39,290 --> 00:37:41,610 and end in the cortex. 622 00:37:41,610 --> 00:37:44,480 Remember, we talked about propriospinal connections. 623 00:37:44,480 --> 00:37:47,860 Well, these are propriocortical connections. 624 00:37:47,860 --> 00:37:51,600 And some of them are just connection within a column. 625 00:37:51,600 --> 00:37:54,190 Others are across columns. 626 00:37:54,190 --> 00:37:58,580 And the others are long transcortical connections. 627 00:37:58,580 --> 00:38:02,176 And those generally go into the white matter. 628 00:38:02,176 --> 00:38:03,550 They go down in the white matter, 629 00:38:03,550 --> 00:38:06,140 and then they travel over a long distance 630 00:38:06,140 --> 00:38:08,030 to another cortical area, where then, they 631 00:38:08,030 --> 00:38:11,320 go back up into the layers of cells. 632 00:38:11,320 --> 00:38:15,270 So this is my picture of a single column where 633 00:38:15,270 --> 00:38:18,180 I've taken the cells and axons and I pulled 634 00:38:18,180 --> 00:38:21,310 them apart a little bit to make it broader than it really would 635 00:38:21,310 --> 00:38:24,440 be so you can see the different types 636 00:38:24,440 --> 00:38:25,710 and how they're connected. 637 00:38:25,710 --> 00:38:28,740 I show one of the large pyramidal cells 638 00:38:28,740 --> 00:38:30,820 in the deep part of layer five. 639 00:38:30,820 --> 00:38:35,460 It has an axon that goes out, generally to subcortical areas. 640 00:38:35,460 --> 00:38:38,690 And I simplify the dendrites because if I drew all of them, 641 00:38:38,690 --> 00:38:41,010 then you wouldn't see the rest of things, 642 00:38:41,010 --> 00:38:43,040 the rest of the cells. 643 00:38:43,040 --> 00:38:45,685 So I'm just giving examples of the major dendrites, 644 00:38:45,685 --> 00:38:48,710 the basal dendrites and apical dendrites, 645 00:38:48,710 --> 00:38:50,210 and I'm showing that they arborize-- 646 00:38:50,210 --> 00:38:54,020 these dendrites arborize up in layer one. 647 00:38:54,020 --> 00:38:58,090 I show a few cells in layer one with a dendritic spread, 648 00:38:58,090 --> 00:39:01,410 and then, longer axon distribution 649 00:39:01,410 --> 00:39:09,200 that's mostly interconnecting adjacent areas of cortex. 650 00:39:09,200 --> 00:39:12,550 Then I show the pyramidal, smaller pyramidal, cells here. 651 00:39:12,550 --> 00:39:16,230 I show the small granule cells in layer four 652 00:39:16,230 --> 00:39:19,540 that are receiving input from the white matter. 653 00:39:19,540 --> 00:39:22,320 This would be an axon coming from the thalamus. 654 00:39:22,320 --> 00:39:25,470 I show where it's main connections are in layer four. 655 00:39:25,470 --> 00:39:27,570 There are other connections. 656 00:39:27,570 --> 00:39:33,230 They also go to layer one and layer five and six. 657 00:39:33,230 --> 00:39:35,630 In fact, they really go to all the layers. 658 00:39:35,630 --> 00:39:37,760 But they're much denser in layer four, 659 00:39:37,760 --> 00:39:41,450 so we often picture those terminating in layer four. 660 00:39:41,450 --> 00:39:44,820 And they're terminating on these excitatory interneurons, which 661 00:39:44,820 --> 00:39:50,960 then have axons that connect to the overlying areas, primarily. 662 00:39:50,960 --> 00:39:54,640 And then I'm showing connections from these layer 663 00:39:54,640 --> 00:39:57,440 six neurons, some of which go out. 664 00:39:57,440 --> 00:39:59,380 They go to the thalamus. 665 00:39:59,380 --> 00:40:03,820 And others go to the other layers. 666 00:40:03,820 --> 00:40:07,810 So these are inter-columnar axons, 667 00:40:07,810 --> 00:40:12,250 several types in layer four, in layer six. 668 00:40:12,250 --> 00:40:18,700 And also from these upper layers where you see-- this is axons. 669 00:40:18,700 --> 00:40:20,917 They almost always have collaterals, 670 00:40:20,917 --> 00:40:22,500 even if they're going to another area. 671 00:40:22,500 --> 00:40:26,480 And this, what do we call this type? 672 00:40:26,480 --> 00:40:30,790 It goes down into the white matter, goes to another area, 673 00:40:30,790 --> 00:40:33,840 then goes back up. 674 00:40:33,840 --> 00:40:39,170 We call it a U-fiber because it's going down, over, then up. 675 00:40:39,170 --> 00:40:40,890 Those are the U-fibers. 676 00:40:40,890 --> 00:40:45,320 These others are intercortical axons that are not U-fibers. 677 00:40:45,320 --> 00:40:47,130 They never go into the white matter. 678 00:40:50,120 --> 00:40:54,180 This is very typical of a-- it's a very simplified 679 00:40:54,180 --> 00:40:56,570 picture of the columnar arrangement 680 00:40:56,570 --> 00:40:58,355 that's repeated throughout the cortex. 681 00:41:01,100 --> 00:41:05,080 This just shows some-- These aren't from Golgi. 682 00:41:05,080 --> 00:41:10,150 They're injected cells in more recent studies. 683 00:41:10,150 --> 00:41:12,610 This is the work of Charlie Gilbert, I believe, 684 00:41:12,610 --> 00:41:16,680 who worked a lot with Hubel and Wiesel, 685 00:41:16,680 --> 00:41:19,330 and has published a lot on these neuron types 686 00:41:19,330 --> 00:41:22,980 in the visual areas of the cat and the monkey. 687 00:41:22,980 --> 00:41:25,692 There's another one where he shows the stellate up 688 00:41:25,692 --> 00:41:31,760 in layer two and three, elaborate dendrites and axon. 689 00:41:37,380 --> 00:41:40,730 So to just talk briefly about the basic sensory motor 690 00:41:40,730 --> 00:41:41,865 functions of the cortex. 691 00:41:44,530 --> 00:41:50,140 We know in the sensory cortex that when 692 00:41:50,140 --> 00:41:53,810 you have motor cortex devoted to a given area of receptors, 693 00:41:53,810 --> 00:41:55,360 you have more acuity. 694 00:41:55,360 --> 00:41:58,200 So if you look at the foveal representation, 695 00:41:58,200 --> 00:42:03,685 visual cortex is much greater than the representation 696 00:42:03,685 --> 00:42:06,800 of the lower acuity regions of our visual field. 697 00:42:06,800 --> 00:42:10,160 The same is true for somatosensory cortex. 698 00:42:10,160 --> 00:42:14,490 So what are the big parts of somatosensory cortex? 699 00:42:14,490 --> 00:42:18,900 Parts representing the fingertips, the tongue, lips; 700 00:42:18,900 --> 00:42:23,310 the parts where our acuity is the most. 701 00:42:23,310 --> 00:42:24,770 The same is true of animals. 702 00:42:24,770 --> 00:42:27,990 Remember when we showed picture of the raccoon. 703 00:42:27,990 --> 00:42:30,080 It's actually got a different gyrus 704 00:42:30,080 --> 00:42:36,070 for each digit-- very high acuity in their front paws. 705 00:42:36,070 --> 00:42:38,530 And the same thing is true in the motor system 706 00:42:38,530 --> 00:42:42,420 where we could talk about motor acuity or dexterity. 707 00:42:42,420 --> 00:42:44,350 We're talking about the hands. 708 00:42:44,350 --> 00:42:46,680 But it's true for other parts, too. 709 00:42:46,680 --> 00:42:53,760 The spider monkeys has high motor acuity in his tail, 710 00:42:53,760 --> 00:42:57,480 so he's got a lot more cortex representing 711 00:42:57,480 --> 00:42:58,790 the movement of that tail. 712 00:43:03,290 --> 00:43:05,870 And of course, that's true for the tongue. 713 00:43:05,870 --> 00:43:09,080 We don't just have high sensory acuity in the tongue, 714 00:43:09,080 --> 00:43:10,290 we have high motor acuity. 715 00:43:10,290 --> 00:43:12,250 We need it not only for speaking, 716 00:43:12,250 --> 00:43:19,130 but for manipulating food and for all the various things 717 00:43:19,130 --> 00:43:21,825 we do with our tongue. 718 00:43:21,825 --> 00:43:25,640 We're probably the best kissers in the animal kingdom because 719 00:43:25,640 --> 00:43:30,540 of that, tremendous control of our tongues. 720 00:43:30,540 --> 00:43:39,250 All right, so, then I bring up this-- 721 00:43:39,250 --> 00:43:42,430 I like to refer to Mesulam because he made this so clear 722 00:43:42,430 --> 00:43:44,870 in his recent writings. 723 00:43:44,870 --> 00:43:49,100 He pictured the paralimbic cortical areas 724 00:43:49,100 --> 00:43:51,700 as divided into two main regions. 725 00:43:51,700 --> 00:43:54,870 Now these are-- the paralimbic cortical 726 00:43:54,870 --> 00:44:01,120 areas are sort of in between the neocortex and the limbic areas. 727 00:44:01,120 --> 00:44:04,650 Some people would say, well, there really are neocortex. 728 00:44:04,650 --> 00:44:08,495 But if you take a strict structural definition 729 00:44:08,495 --> 00:44:11,230 of neocortex, they don't really have 730 00:44:11,230 --> 00:44:14,620 the same kind of six layers. 731 00:44:14,620 --> 00:44:16,840 You could easily name six layers there, 732 00:44:16,840 --> 00:44:18,700 but they're a little bit simpler cortex. 733 00:44:18,700 --> 00:44:24,020 But they're always in between neocortex and limbic areas. 734 00:44:24,020 --> 00:44:25,490 In fact, a lot of the connections 735 00:44:25,490 --> 00:44:28,510 going both ways from these paralimbic areas, 736 00:44:28,510 --> 00:44:32,920 but the two regions correspond to what 737 00:44:32,920 --> 00:44:37,200 we've been talking about, a place sense and object sense. 738 00:44:37,200 --> 00:44:39,430 So let's just look at his picture here. 739 00:44:39,430 --> 00:44:43,280 Here, I put this in the book. 740 00:44:43,280 --> 00:44:46,240 I think we redrew it, but not very much. 741 00:44:46,240 --> 00:44:51,620 And it shows the cingulate gy-- all the away from parolfactory 742 00:44:51,620 --> 00:44:53,450 just beyond the anterior cingulate 743 00:44:53,450 --> 00:44:57,050 here, through the entire cingulate gyrus 744 00:44:57,050 --> 00:45:00,840 and retrosplenial cortex, and then continuous 745 00:45:00,840 --> 00:45:03,980 with the whole parahippocampal area. 746 00:45:03,980 --> 00:45:07,500 So the parahippocampal gyrus in humans is part of that. 747 00:45:07,500 --> 00:45:10,870 So that's hippocampocentric. 748 00:45:10,870 --> 00:45:15,430 These areas all connect with parahippocampal areas, 749 00:45:15,430 --> 00:45:17,037 which connect to the hippocampus. 750 00:45:17,037 --> 00:45:19,087 They connect to entorhinal cortex, for example. 751 00:45:22,010 --> 00:45:27,237 These other areas he called olfactocentric. 752 00:45:27,237 --> 00:45:29,640 This is interesting because the connections 753 00:45:29,640 --> 00:45:34,150 of all these regions are different than the ones-- 754 00:45:34,150 --> 00:45:36,710 than the hippocampocentric areas. 755 00:45:36,710 --> 00:45:38,500 They go, for example, they're heavily 756 00:45:38,500 --> 00:45:44,190 connected to the amygdala and basal forebrain, the areas that 757 00:45:44,190 --> 00:45:46,640 are evolved. 758 00:45:46,640 --> 00:45:49,800 They're closely connected to the olfactory system, 759 00:45:49,800 --> 00:45:54,550 and to these systems that evolve for object discrimination 760 00:45:54,550 --> 00:45:58,565 or our affective responses to objects. 761 00:46:02,710 --> 00:46:05,960 And then, I go through one other thing that 762 00:46:05,960 --> 00:46:08,370 played a critical role in evolution 763 00:46:08,370 --> 00:46:11,150 of the somatosensory system that were 764 00:46:11,150 --> 00:46:14,340 one of the somatosensory areas specialized 765 00:46:14,340 --> 00:46:16,880 for controlling fine movement, and that's 766 00:46:16,880 --> 00:46:20,740 what we call primary motor cortex. 767 00:46:20,740 --> 00:46:24,320 What's the evidence that it actually-- the motor cortex 768 00:46:24,320 --> 00:46:27,320 evolved out of the somatosensory area? 769 00:46:27,320 --> 00:46:29,830 For one thing, it does get some somatosensory input. 770 00:46:32,870 --> 00:46:36,160 It's adjacent to, just rostral, to what 771 00:46:36,160 --> 00:46:38,060 we call somatosensory area one. 772 00:46:41,220 --> 00:46:45,390 But in some animals, it's actually not separate, 773 00:46:45,390 --> 00:46:48,280 like the Virginia Opossum. 774 00:46:48,280 --> 00:46:49,563 Remember this? 775 00:46:49,563 --> 00:46:51,095 Do I have a picture here? 776 00:46:53,640 --> 00:46:55,100 I guess I didn't put it here. 777 00:47:01,720 --> 00:47:04,200 But that motor cortex was so critical, 778 00:47:04,200 --> 00:47:11,830 except we can tell which area it is because the ventral anterior 779 00:47:11,830 --> 00:47:15,510 nucleus and the ventral lateral nucleus, 780 00:47:15,510 --> 00:47:18,260 the parts the anterior to the somatosensory part 781 00:47:18,260 --> 00:47:24,490 of the thalamus, project to the motor areas, the VL and the VA. 782 00:47:28,890 --> 00:47:32,250 We usually can separate them, even in the opossum. 783 00:47:32,250 --> 00:47:35,610 The VL gets the cerebellar inputs primarily. 784 00:47:35,610 --> 00:47:39,130 The VA gets striatal outputs primarily, 785 00:47:39,130 --> 00:47:42,540 and it projects to the premotor areas. 786 00:47:42,540 --> 00:47:46,520 VL projects to the motor cortex. 787 00:47:46,520 --> 00:47:53,370 But in the opossum, these nuclei project to the very same cortex 788 00:47:53,370 --> 00:47:57,354 that the ventral posterior nucleus projects, 789 00:47:57,354 --> 00:47:58,270 so it's somatosensory. 790 00:48:01,160 --> 00:48:06,680 All right, and what evolved as association areas right 791 00:48:06,680 --> 00:48:11,370 in front of these motor areas are the areas involved 792 00:48:11,370 --> 00:48:17,980 in anticipating and planning became the locus 793 00:48:17,980 --> 00:48:22,665 of the executive functions of the prefrontal cortex, which 794 00:48:22,665 --> 00:48:25,180 is so critical for human behavior. 795 00:48:25,180 --> 00:48:27,550 But it's very important in animals, too. 796 00:48:27,550 --> 00:48:33,160 This ability to anticipate, to get inputs 797 00:48:33,160 --> 00:48:36,410 from posterior areas, like from the visual system, 798 00:48:36,410 --> 00:48:41,010 to tell them where the locations of things 799 00:48:41,010 --> 00:48:43,920 that were just in the environment, scanning, 800 00:48:43,920 --> 00:48:46,660 that we're scanning. 801 00:48:46,660 --> 00:48:49,550 Retain that information briefly in working memory, 802 00:48:49,550 --> 00:48:52,235 and that's affecting where we move our eyes, where 803 00:48:52,235 --> 00:48:54,570 we choose to move our eyes. 804 00:48:54,570 --> 00:49:02,750 All right we'll come back here with this slide. 805 00:49:02,750 --> 00:49:04,730 And then we'll go on and talk a little bit more 806 00:49:04,730 --> 00:49:07,900 about structural details in the hippocampus next time. 807 00:49:07,900 --> 00:49:10,960 But please read through all these qualities. 808 00:49:10,960 --> 00:49:14,125 And they're all online, so we won't 809 00:49:14,125 --> 00:49:15,930 have to spend so much time with the rest 810 00:49:15,930 --> 00:49:20,031 of this particular group of chapter 32 things.