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 00:00:23,270 --> 00:00:25,640 PROFESSOR: I just got these from [INAUDIBLE]. 9 00:00:25,640 --> 00:00:30,580 Now, some of you wanted to see those simulations using 10 00:00:30,580 --> 00:00:34,590 screen characters sort of watching 11 00:00:34,590 --> 00:00:41,220 these robotic characters with motivations that have dynamics 12 00:00:41,220 --> 00:00:49,930 similar to what is suggested first from ecological studies 13 00:00:49,930 --> 00:00:55,980 but also from studies of hypothalamic neurons. 14 00:00:55,980 --> 00:00:58,260 So I will post these. 15 00:01:03,300 --> 00:01:05,910 I should post them under the hypothalamus chapter, 16 00:01:05,910 --> 00:01:11,630 but maybe I'll just send them by email to all of you 17 00:01:11,630 --> 00:01:12,950 so you can take a look. 18 00:01:28,720 --> 00:01:29,370 All right. 19 00:01:36,530 --> 00:01:40,540 We finished with the Chapter 26 material, 20 00:01:40,540 --> 00:01:46,650 which was the introduction to hippocampal and other limbic 21 00:01:46,650 --> 00:01:51,020 system pathways, particularly the Papez circuit. 22 00:01:51,020 --> 00:01:54,370 And we'll come back to that right 23 00:01:54,370 --> 00:01:57,925 after this, a little section here on hormonal influences. 24 00:02:01,590 --> 00:02:06,540 Because I want to deal with both hippocampus and then amygdala 25 00:02:06,540 --> 00:02:13,120 and the more anterior parts of intra-striatum before we 26 00:02:13,120 --> 00:02:15,395 go on to corpus striatum and neocortex. 27 00:02:19,110 --> 00:02:22,700 So the major topics in this little unit 28 00:02:22,700 --> 00:02:25,700 are sexual differentiation of the-- especially 29 00:02:25,700 --> 00:02:33,970 the human hypothalamus, emergence of male/female brain 30 00:02:33,970 --> 00:02:38,140 differences, and determinants of sexual orientation. 31 00:02:38,140 --> 00:02:40,950 Studies have been done of that. 32 00:02:40,950 --> 00:02:44,439 And then a little bit on bird song, 33 00:02:44,439 --> 00:02:45,980 because of the importance of hormonal 34 00:02:45,980 --> 00:02:51,075 as well as other determinants and the discoveries 35 00:02:51,075 --> 00:02:52,900 that have been made in that field. 36 00:02:56,010 --> 00:02:58,680 Other relevant topics concerning actions 37 00:02:58,680 --> 00:03:09,680 of estrogen on the brain, the use of [INAUDIBLE] cultures, 38 00:03:09,680 --> 00:03:11,716 usually slice cultures, with a look 39 00:03:11,716 --> 00:03:17,030 at effects of hormones on differentiation of neurons. 40 00:03:17,030 --> 00:03:20,680 That's how we know that it's probably not just hypothalamus, 41 00:03:20,680 --> 00:03:24,640 not just a few areas that have been-- things that have been 42 00:03:24,640 --> 00:03:29,330 discovered so far, but they discovered that, for example, 43 00:03:29,330 --> 00:03:32,890 the catecholamine systems in tissue culture 44 00:03:32,890 --> 00:03:35,530 are influenced by sexual hormones as well. 45 00:03:38,510 --> 00:03:39,010 All right. 46 00:03:43,320 --> 00:03:46,660 A related topic is the effects of thyroid hormones. 47 00:03:46,660 --> 00:03:49,130 And here, this is an important one, 48 00:03:49,130 --> 00:03:54,440 because thyroid-- particular thyroid hormones are 49 00:03:54,440 --> 00:03:58,170 known to be very important in brain development 50 00:03:58,170 --> 00:04:05,300 with abnormalities in thyroid, for example, 51 00:04:05,300 --> 00:04:08,570 consistently leads to deficiencies in cerebellar 52 00:04:08,570 --> 00:04:12,550 development, but other brain areas can be affected as well. 53 00:04:12,550 --> 00:04:13,260 Mostly t4. 54 00:04:20,190 --> 00:04:25,510 And one reason that in recent years 55 00:04:25,510 --> 00:04:27,050 there's been more attention to this 56 00:04:27,050 --> 00:04:34,100 is because of pollutants that mimic-- 57 00:04:34,100 --> 00:04:36,400 that bind to thyroid receptors. 58 00:04:36,400 --> 00:04:39,240 And when this happens in the nervous system 59 00:04:39,240 --> 00:04:42,920 during development, it can cause brain abnormalities. 60 00:04:42,920 --> 00:04:44,505 There's some evidence from animals. 61 00:04:47,180 --> 00:04:51,040 That was the topic the led me to work 62 00:04:51,040 --> 00:05:01,100 with Eric Montie on the brains of sea mammals, particularly 63 00:05:01,100 --> 00:05:03,790 the Atlantic white sided dolphin. 64 00:05:03,790 --> 00:05:09,200 And also we did some work on California sea lion. 65 00:05:09,200 --> 00:05:11,920 California sea lions, not because of thyroid hormone, 66 00:05:11,920 --> 00:05:15,270 but because of their exposure to pollutants-- 67 00:05:15,270 --> 00:05:17,680 natural pollutants-- that they encounter 68 00:05:17,680 --> 00:05:20,340 in their environment in Southern California 69 00:05:20,340 --> 00:05:22,440 that cause brain abnormalities. 70 00:05:27,090 --> 00:05:31,175 They can practically wipe out the hippocampus, for example. 71 00:05:38,930 --> 00:05:42,720 This is Montie here. 72 00:05:42,720 --> 00:05:44,570 This was his PhD thesis. 73 00:05:44,570 --> 00:05:47,090 I was one of his committee members, 74 00:05:47,090 --> 00:05:51,250 and he worked closely with me for part of his project 75 00:05:51,250 --> 00:05:57,000 because he needed to-- he was basically doing the control 76 00:05:57,000 --> 00:06:02,620 studies for his work on pollutant effects 77 00:06:02,620 --> 00:06:05,410 and he needed help in identifying 78 00:06:05,410 --> 00:06:09,330 various structures from the MRI images. 79 00:06:09,330 --> 00:06:13,950 So I went down to Woods Hole a number of times, 80 00:06:13,950 --> 00:06:16,790 and he also sent me images to help him 81 00:06:16,790 --> 00:06:18,680 with the identifications. 82 00:06:18,680 --> 00:06:21,010 And that resulted in some publications. 83 00:06:21,010 --> 00:06:25,365 If you look up Eric Montie online or Montie and myself, 84 00:06:25,365 --> 00:06:27,340 and there were a couple other authors, too. 85 00:06:27,340 --> 00:06:30,150 People at Woods Hole that were involved in some way 86 00:06:30,150 --> 00:06:32,390 in getting the brains that we used. 87 00:06:37,930 --> 00:06:40,100 And I just mention this one website 88 00:06:40,100 --> 00:06:43,925 because it's particularly good for the thyroid hormone 89 00:06:43,925 --> 00:06:44,425 information. 90 00:06:50,830 --> 00:06:57,050 When we-- if we're interested in sex differences 91 00:06:57,050 --> 00:07:01,140 between male and female brains, particularly in humans, 92 00:07:01,140 --> 00:07:04,380 what are the three factors that are likely to play a roll? 93 00:07:04,380 --> 00:07:08,170 What are the things that we look for? 94 00:07:08,170 --> 00:07:16,410 Hormonal effects, genetic effects, and environment, 95 00:07:16,410 --> 00:07:17,905 learning of some sort. 96 00:07:20,670 --> 00:07:25,230 And we know from many studies that although all three have 97 00:07:25,230 --> 00:07:31,610 effects, when it comes to sexual orientation, 98 00:07:31,610 --> 00:07:33,810 environment doesn't seem to have-- 99 00:07:33,810 --> 00:07:35,650 isn't a major determinant at all. 100 00:07:35,650 --> 00:07:38,800 It's genetic effects and hormonal effects. 101 00:07:42,350 --> 00:07:48,170 So the neuroanatomical studies of sex differences 102 00:07:48,170 --> 00:07:52,450 received a big impetus when there was a neuroscientist who 103 00:07:52,450 --> 00:07:56,620 was also a gay man working at Harvard. 104 00:07:56,620 --> 00:07:58,725 A lot of his work was with Hubel and Wiesel. 105 00:08:02,550 --> 00:08:05,160 Began working on this topic, and he 106 00:08:05,160 --> 00:08:09,260 was able to obtain results of homosexual males 107 00:08:09,260 --> 00:08:13,680 and normal males and started doing comparisons. 108 00:08:13,680 --> 00:08:16,410 And of course, he was concerned with male/female differences 109 00:08:16,410 --> 00:08:16,930 as well. 110 00:08:16,930 --> 00:08:23,290 And that led to a lot-- a whole series of studies, 111 00:08:23,290 --> 00:08:28,500 not just-- this was not just by him, but by others as well. 112 00:08:28,500 --> 00:08:30,460 So I just want to review some of that here. 113 00:08:33,630 --> 00:08:35,090 His name is Simon LeVay. 114 00:08:35,090 --> 00:08:37,159 Very good neuroscientist. 115 00:08:37,159 --> 00:08:43,480 L-E-V-A-Y. I think capital V-A-Y. Simon LeVay. 116 00:08:43,480 --> 00:08:46,505 Very good neuroscientist and good friend of a lot of us 117 00:08:46,505 --> 00:08:47,255 in neuroscientist. 118 00:08:57,160 --> 00:08:59,625 OK, that just summarizes what I just said. 119 00:09:05,050 --> 00:09:07,270 I believe I reproduced this table in the book 120 00:09:07,270 --> 00:09:12,370 because this is from Schwab studies. 121 00:09:12,370 --> 00:09:15,860 Martin Schwab has done a lot of work on this topic, 122 00:09:15,860 --> 00:09:18,300 and his studies are often referred 123 00:09:18,300 --> 00:09:22,310 to because he was one of the earlier ones 124 00:09:22,310 --> 00:09:25,050 to really put emphasis on it in his work. 125 00:09:25,050 --> 00:09:27,870 And he collected all these data. 126 00:09:27,870 --> 00:09:30,320 These are references he refers to in his paper, 127 00:09:30,320 --> 00:09:31,250 if you look it up. 128 00:09:31,250 --> 00:09:37,280 His Trends in Neuroscience paper back in '95. 129 00:09:37,280 --> 00:09:41,800 And he lists these different diseases because they were-- 130 00:09:41,800 --> 00:09:45,700 and for all of them, they were-- the frequency of occurrence 131 00:09:45,700 --> 00:09:48,490 was different for males and females. 132 00:09:48,490 --> 00:09:52,760 Look how asymmetric it is for, like, anorexia nervosa. 133 00:09:52,760 --> 00:09:57,260 93& female, 7% male. 134 00:09:57,260 --> 00:09:59,110 Or bulimia. 135 00:09:59,110 --> 00:10:02,020 One particular type of schizophrenia, 136 00:10:02,020 --> 00:10:07,080 whereas most types of schizophrenia only 27% 137 00:10:07,080 --> 00:10:09,920 females, 73% male. 138 00:10:09,920 --> 00:10:16,090 But for that one type, it's different. 139 00:10:16,090 --> 00:10:22,780 And then look at the ones that males are dominant. 140 00:10:22,780 --> 00:10:27,020 Dyslexia is very well-known for that. 141 00:10:27,020 --> 00:10:28,540 Sleep apnea. 142 00:10:28,540 --> 00:10:29,460 Tourette syndrome. 143 00:10:29,460 --> 00:10:30,331 Yes. 144 00:10:30,331 --> 00:10:31,247 AUDIENCE: [INAUDIBLE]. 145 00:10:45,525 --> 00:10:47,150 PROFESSOR: That's a very good question. 146 00:10:47,150 --> 00:10:53,410 I don't know the answer, but that's-- I mentioned when I 147 00:10:53,410 --> 00:10:56,370 listed these extra credit that if you can come up with 148 00:10:56,370 --> 00:10:59,830 something like that, a question that you can find something, 149 00:10:59,830 --> 00:11:02,750 please do so and we'll give you extra credit for it. 150 00:11:02,750 --> 00:11:04,905 Be useful for the whole class. 151 00:11:07,500 --> 00:11:10,540 But because of these kinds of differences, I mean, 152 00:11:10,540 --> 00:11:12,400 it becomes obvious that there has 153 00:11:12,400 --> 00:11:15,600 to be differences in male and female brains. 154 00:11:15,600 --> 00:11:18,776 And one of those differences could actually be structural. 155 00:11:18,776 --> 00:11:20,900 Of course, we're more concerned with the structural 156 00:11:20,900 --> 00:11:22,490 differences, but with any differences, 157 00:11:22,490 --> 00:11:25,940 it could cause functional differences in the brain. 158 00:11:28,460 --> 00:11:32,960 So a place to start is, well, when 159 00:11:32,960 --> 00:11:36,980 are-- when are there differences in gonadal hormone levels? 160 00:11:36,980 --> 00:11:42,510 When are they at a peak, that is, during human development. 161 00:11:42,510 --> 00:11:46,240 There's actually three different periods when they reach a peak. 162 00:11:46,240 --> 00:11:50,680 One is the early prenatal, first half of gestation, 163 00:11:50,680 --> 00:11:51,980 during the formation. 164 00:11:51,980 --> 00:11:55,420 That's the period when genitalia are forming. 165 00:11:55,420 --> 00:11:58,510 Then perinatally, there's another peak. 166 00:11:58,510 --> 00:12:03,090 And then the levels are lower again until puberty, 167 00:12:03,090 --> 00:12:07,830 of course, when the differences we're most familiar with 168 00:12:07,830 --> 00:12:10,400 appear. 169 00:12:10,400 --> 00:12:12,360 But if you look for structural differences 170 00:12:12,360 --> 00:12:14,750 in the hypothalamus, the studies that have been done 171 00:12:14,750 --> 00:12:20,030 indicate that, at least for the sexually dimorphic nucleus 172 00:12:20,030 --> 00:12:22,400 of the anterior hypothalamus, the one that's 173 00:12:22,400 --> 00:12:25,330 received the most attention, the differences 174 00:12:25,330 --> 00:12:28,560 don't appear until about age four. 175 00:12:28,560 --> 00:12:33,925 So that's when the hormonal peaks are going down. 176 00:12:36,650 --> 00:12:43,420 And so this is-- first of all, I should show you where it is. 177 00:12:43,420 --> 00:12:50,010 This is a section that is about at this level or just anterior 178 00:12:50,010 --> 00:12:53,050 to this level in these diagrams. 179 00:12:53,050 --> 00:12:55,970 These are black/white versions of the color ones 180 00:12:55,970 --> 00:12:58,640 I used in the book. 181 00:12:58,640 --> 00:13:02,330 But here are the curves, and you can see there's some scatter, 182 00:13:02,330 --> 00:13:05,120 but the males are in the solid points 183 00:13:05,120 --> 00:13:10,510 and the female brains are in the open circles. 184 00:13:10,510 --> 00:13:21,480 And for the males here, the squares 185 00:13:21,480 --> 00:13:24,330 indicate a homosexual man, and you 186 00:13:24,330 --> 00:13:28,350 know that when this nucleus is concerned, 187 00:13:28,350 --> 00:13:34,440 the homosexual brains are-- not that homosexual males don't 188 00:13:34,440 --> 00:13:38,010 show female brain characteristics at all. 189 00:13:38,010 --> 00:13:43,080 They fit the curve of changing sides 190 00:13:43,080 --> 00:13:46,563 of this nucleus-- it's size, number of neurons. 191 00:13:51,150 --> 00:13:52,560 The fit the male curve. 192 00:13:52,560 --> 00:13:54,720 And the differences you can see here, 193 00:13:54,720 --> 00:14:00,610 up here, this is-- if we take this as when they appear, 194 00:14:00,610 --> 00:14:03,290 that's about four years old. 195 00:14:03,290 --> 00:14:06,370 Before that, there were no differences 196 00:14:06,370 --> 00:14:08,395 that have been seen in hypothalamic areas. 197 00:14:14,020 --> 00:14:16,600 It's called the sexually dimorphic nucleus, 198 00:14:16,600 --> 00:14:18,890 the preoptic area of the human hypothalamus. 199 00:14:18,890 --> 00:14:19,980 So it's pretty anterior. 200 00:14:24,180 --> 00:14:29,840 What is a problem with doing this kind of work? 201 00:14:29,840 --> 00:14:33,200 It's a major technical factor. 202 00:14:33,200 --> 00:14:37,970 The problem is if you're looking at volume of brain tissue, 203 00:14:37,970 --> 00:14:39,900 there's a lot of factors that can affect that, 204 00:14:39,900 --> 00:14:44,150 and one of them that will affect it is-- in fact, even 205 00:14:44,150 --> 00:14:46,510 your ability to differentiate the nucleus 206 00:14:46,510 --> 00:14:48,980 can be affected just by the tissue fixation. 207 00:14:48,980 --> 00:14:51,310 It varies so much in human tissue. 208 00:14:51,310 --> 00:14:54,990 It's not like doing a study of rats or monkeys, 209 00:14:54,990 --> 00:14:58,420 where you can control that. 210 00:14:58,420 --> 00:14:59,045 There are laws. 211 00:14:59,045 --> 00:15:01,175 The laws differ in different areas. 212 00:15:01,175 --> 00:15:04,910 But you don't just profuse human beings. 213 00:15:04,910 --> 00:15:08,990 The only really well-fixed human tissue 214 00:15:08,990 --> 00:15:10,960 we have that appears in the textbooks 215 00:15:10,960 --> 00:15:12,760 is from a guy that committed suicide 216 00:15:12,760 --> 00:15:14,140 by drinking formaldehyde. 217 00:15:14,140 --> 00:15:19,414 And he has a beautiful tissue in his digestive tract. 218 00:15:19,414 --> 00:15:20,830 Sorry. 219 00:15:20,830 --> 00:15:24,930 So it's a big problem for brain. 220 00:15:24,930 --> 00:15:26,960 I don't know anybody who's committed suicide 221 00:15:26,960 --> 00:15:29,656 by perfusing his whole body. 222 00:15:32,430 --> 00:15:33,280 OK. 223 00:15:33,280 --> 00:15:35,826 And of course, it varies with the tissue-- 224 00:15:35,826 --> 00:15:38,225 the fixative used as well. 225 00:15:38,225 --> 00:15:40,575 But mostly just time before fixation. 226 00:15:40,575 --> 00:15:43,390 So The solution is to do cell counts 227 00:15:43,390 --> 00:15:45,830 and use only brains where you can actually 228 00:15:45,830 --> 00:15:50,180 identify the structure, not just have to go by gross location, 229 00:15:50,180 --> 00:15:55,780 but actually identify it from the [INAUDIBLE] architecture. 230 00:15:55,780 --> 00:15:57,610 The problem is that's a lot harder 231 00:15:57,610 --> 00:16:00,060 to do than just looking at volume. 232 00:16:00,060 --> 00:16:01,830 If you do a series of cross sections 233 00:16:01,830 --> 00:16:06,350 and take the area of a nucleus of each point 234 00:16:06,350 --> 00:16:08,130 and integrate over the structure, 235 00:16:08,130 --> 00:16:11,280 you will get a good estimate of the volume. 236 00:16:11,280 --> 00:16:15,580 But these factors make cell number to be much better. 237 00:16:15,580 --> 00:16:18,690 But there are good methods for estimating number 238 00:16:18,690 --> 00:16:23,320 where you don't have to look at every single section 239 00:16:23,320 --> 00:16:25,239 and you count. 240 00:16:25,239 --> 00:16:26,780 One of the problems there is you want 241 00:16:26,780 --> 00:16:30,370 to come only cells, say, that the nucleolus so you 242 00:16:30,370 --> 00:16:32,380 don't count the cell twice, because it's 243 00:16:32,380 --> 00:16:34,710 cut through more than once in your sections. 244 00:16:37,970 --> 00:16:44,253 OK, so let's look for cell groups that are different. 245 00:16:47,330 --> 00:16:50,000 Additional structures besides that sexually 246 00:16:50,000 --> 00:16:53,960 dimorphic nucleus, the preoptic area had been found. 247 00:16:53,960 --> 00:16:57,780 And there is a nucleus that-- first discovered 248 00:16:57,780 --> 00:17:01,090 in rats, verified in humans-- that 249 00:17:01,090 --> 00:17:05,530 does differ according to sexual orientation. 250 00:17:05,530 --> 00:17:07,770 And then there are sex differences in the CNS 251 00:17:07,770 --> 00:17:09,770 outside the hypothalamus, too. 252 00:17:09,770 --> 00:17:12,490 These have been discovered particularly 253 00:17:12,490 --> 00:17:17,500 by magnetic resonance imaging methods. 254 00:17:17,500 --> 00:17:19,930 So this is the one I showed you. 255 00:17:19,930 --> 00:17:25,590 This is that-- it's also called the sexually dimorphic nucleus 256 00:17:25,590 --> 00:17:30,920 now, but the earlier name was the interstitial nucleus 257 00:17:30,920 --> 00:17:32,610 of the anterior hypothalamus. 258 00:17:32,610 --> 00:17:37,860 Interstitial because it's among the fibers of the [INAUDIBLE]. 259 00:17:44,250 --> 00:17:47,090 But here is another nucleus that's 260 00:17:47,090 --> 00:17:57,870 been found to be different in gay men from normal men. 261 00:17:57,870 --> 00:18:00,880 So I have some of those. 262 00:18:00,880 --> 00:18:03,270 That's the suprachiasmatic nucleus, 263 00:18:03,270 --> 00:18:05,230 which we talked about before because it's 264 00:18:05,230 --> 00:18:07,180 the site of some of these neurons 265 00:18:07,180 --> 00:18:11,060 have that roughly 24-hour rhythm and represent 266 00:18:11,060 --> 00:18:14,720 the biological clock. 267 00:18:14,720 --> 00:18:17,250 So here was the initial report, which 268 00:18:17,250 --> 00:18:19,600 was a paper in Schwab and Hoffman 269 00:18:19,600 --> 00:18:22,910 in brain research back in 1990. 270 00:18:22,910 --> 00:18:26,450 They reported an enlarged suprachiasmatic nucleus 271 00:18:26,450 --> 00:18:29,100 in homosexual men. 272 00:18:29,100 --> 00:18:33,960 1.7 times as large compared to controls. 273 00:18:33,960 --> 00:18:37,330 It contained 2.1 times as many cells. 274 00:18:37,330 --> 00:18:40,920 So it's a pretty striking difference. 275 00:18:40,920 --> 00:18:45,360 The sexually dimorphic nucleus doesn't 276 00:18:45,360 --> 00:18:47,670 differ among homosexuals and normals 277 00:18:47,670 --> 00:18:49,795 in either volume or cell number. 278 00:18:53,210 --> 00:18:55,935 It basically doesn't support the original idea 279 00:18:55,935 --> 00:18:58,560 that they were testing, that homosexual men have 280 00:18:58,560 --> 00:18:59,930 a female hypothalamus. 281 00:18:59,930 --> 00:19:01,060 That's not true at all. 282 00:19:06,240 --> 00:19:09,280 But of course, among homosexual males, 283 00:19:09,280 --> 00:19:12,935 some of them are certainly more male-like and some of them are 284 00:19:12,935 --> 00:19:16,070 more female-like, and they don't-- these studies have sort 285 00:19:16,070 --> 00:19:16,840 of ignored that. 286 00:19:16,840 --> 00:19:17,920 I'm not sure why. 287 00:19:17,920 --> 00:19:19,650 Seems to me that would be important. 288 00:19:23,360 --> 00:19:28,440 They did find male and females do 289 00:19:28,440 --> 00:19:30,510 differ in the suprachiasmatic nucleus 290 00:19:30,510 --> 00:19:36,030 just by shape of the nucleus. 291 00:19:36,030 --> 00:19:39,190 Also changes with age and with Alzheimer's. 292 00:19:51,000 --> 00:19:52,910 But this was their first report that 293 00:19:52,910 --> 00:19:56,040 said homosexuals don't have a female hypothalamus. 294 00:19:56,040 --> 00:20:02,790 And then how would you answer this question now? 295 00:20:02,790 --> 00:20:05,260 What appears to be a major cause of variation 296 00:20:05,260 --> 00:20:06,965 in sexual orientation in humans? 297 00:20:12,820 --> 00:20:14,920 You could say hormones, but in fact there's 298 00:20:14,920 --> 00:20:18,950 more data to indicate its genetic. 299 00:20:18,950 --> 00:20:24,430 Dean Hammer of the NIH was the first to get clear evidence 300 00:20:24,430 --> 00:20:27,720 for genetic differences, and that's 301 00:20:27,720 --> 00:20:29,650 been supported by others. 302 00:20:29,650 --> 00:20:32,652 But we'll talk more about genetic differences 303 00:20:32,652 --> 00:20:34,850 in a few minutes. 304 00:20:34,850 --> 00:20:37,420 There are other sex differences in the brains reported 305 00:20:37,420 --> 00:20:39,980 that are harder to study. 306 00:20:39,980 --> 00:20:42,860 I remember a study in rats and in hamsters 307 00:20:42,860 --> 00:20:48,080 that shows that-- I think it was first in hamsters-- where they 308 00:20:48,080 --> 00:20:51,270 show a difference in dendritic length in certain nuclei 309 00:20:51,270 --> 00:20:53,130 of the hypothalamus. 310 00:20:53,130 --> 00:20:55,615 What does that mean, if the dendrites are longer? 311 00:20:55,615 --> 00:20:59,340 There are also differences in spines, like spine length 312 00:20:59,340 --> 00:21:02,235 and spine density. 313 00:21:02,235 --> 00:21:04,250 Well, what are dendrites doing? 314 00:21:07,192 --> 00:21:11,750 That's where axons are making synaptic connections. 315 00:21:11,750 --> 00:21:15,226 The spines generally won't exist unless those connections 316 00:21:15,226 --> 00:21:15,725 are made. 317 00:21:20,040 --> 00:21:23,790 So differences in spines and in dendritic length 318 00:21:23,790 --> 00:21:26,750 implies differences in connections or numbers 319 00:21:26,750 --> 00:21:28,260 of connections. 320 00:21:28,260 --> 00:21:30,940 So even if the cell number is the same, 321 00:21:30,940 --> 00:21:32,730 there could be differences. 322 00:21:32,730 --> 00:21:36,930 And that's what the studies of dendritic length indicate-- 323 00:21:36,930 --> 00:21:38,250 that we can't-- very difficult. 324 00:21:38,250 --> 00:21:44,290 You can't get that kind of data on human brains-- adult brains. 325 00:21:44,290 --> 00:21:46,060 Golgi doesn't work well, particularly 326 00:21:46,060 --> 00:21:47,810 in poorly fixed tissue, but it doesn't 327 00:21:47,810 --> 00:21:50,475 work very well in mature brains at all. 328 00:21:50,475 --> 00:21:52,300 It works better in younger brains. 329 00:21:55,730 --> 00:22:01,180 So there's probably a lot more sexual dimorphism than 330 00:22:01,180 --> 00:22:04,620 we're-- than we've really found so far. 331 00:22:12,920 --> 00:22:15,120 OK, let's go to a different area where 332 00:22:15,120 --> 00:22:17,960 there is a very clear sexual difference. 333 00:22:17,960 --> 00:22:20,560 This has been found by a totally different group 334 00:22:20,560 --> 00:22:23,700 of investigators-- people that were initially 335 00:22:23,700 --> 00:22:28,780 studying rats and looking at the spinal cord. 336 00:22:28,780 --> 00:22:35,160 They found a sexually dimorphic area in the sacral region. 337 00:22:35,160 --> 00:22:38,570 The nucleus of the bulbocavernosus 338 00:22:38,570 --> 00:22:41,450 or bulbospongiosus, it's sometimes called. 339 00:22:41,450 --> 00:22:44,440 This is the muscle involved in engorgement 340 00:22:44,440 --> 00:22:48,480 of genitals in both males and females. 341 00:22:48,480 --> 00:22:52,930 But the nucleus is considerably bigger in males, 342 00:22:52,930 --> 00:22:55,595 probably because the organ is bigger. 343 00:22:55,595 --> 00:22:56,470 The muscle is bigger. 344 00:22:59,120 --> 00:23:03,430 And there are other differences, too. 345 00:23:03,430 --> 00:23:06,380 I mentioned imaging methods have confirmed 346 00:23:06,380 --> 00:23:09,530 what was known from brain collections 347 00:23:09,530 --> 00:23:11,620 earlier, that the size of the corpus callosum 348 00:23:11,620 --> 00:23:15,290 is larger in females. 349 00:23:15,290 --> 00:23:20,790 The fact is the larger-- the smaller corpus callosum 350 00:23:20,790 --> 00:23:24,790 size in males indicates that the male brain may 351 00:23:24,790 --> 00:23:27,890 be more compartmentalized, less integrated, 352 00:23:27,890 --> 00:23:29,860 between the hemispheres than in females. 353 00:23:29,860 --> 00:23:32,470 And in fact there is behavioral data 354 00:23:32,470 --> 00:23:36,540 to indicate greater left hemisphere dominance 355 00:23:36,540 --> 00:23:38,910 in language, for example, males. 356 00:23:38,910 --> 00:23:45,470 That's why the frequency of severe aphasia after lesions 357 00:23:45,470 --> 00:23:49,010 of the left hemisphere, the aphasia 358 00:23:49,010 --> 00:23:52,200 tends to be worse in males than in females. 359 00:23:52,200 --> 00:23:54,040 Females are much more likely to have 360 00:23:54,040 --> 00:23:56,980 some language in the right hemispheres as well. 361 00:23:56,980 --> 00:23:57,903 Yes? 362 00:23:57,903 --> 00:23:58,819 AUDIENCE: [INAUDIBLE]. 363 00:24:06,575 --> 00:24:07,200 PROFESSOR: Yes. 364 00:24:07,200 --> 00:24:11,170 There are various structural details that differ, too. 365 00:24:11,170 --> 00:24:13,530 For example, if you look-- especially 366 00:24:13,530 --> 00:24:16,400 we know it for the planum temporale. 367 00:24:16,400 --> 00:24:20,110 This is right around the auditory region of cortex. 368 00:24:20,110 --> 00:24:21,830 There are a number of differences. 369 00:24:21,830 --> 00:24:28,360 If you look under Galaburda in the literature-- 370 00:24:28,360 --> 00:24:29,760 another good homework project. 371 00:24:29,760 --> 00:24:32,790 Al Galaburda has worked for years at the Beth Israel 372 00:24:32,790 --> 00:24:34,870 Hospital here in Boston. 373 00:24:34,870 --> 00:24:36,860 Has done a number of studies in human brains. 374 00:24:36,860 --> 00:24:39,810 In more recent years, he's done less than humans, 375 00:24:39,810 --> 00:24:42,250 but in fact, I think he made his biggest impact 376 00:24:42,250 --> 00:24:43,840 by his studies of human brains. 377 00:24:43,840 --> 00:24:48,930 He worked under Norman Geschwind for a long time, a very 378 00:24:48,930 --> 00:24:53,110 well-known behavioral neurologists in Boston. 379 00:24:53,110 --> 00:24:56,210 He died a number of years ago, but Al was much younger 380 00:24:56,210 --> 00:24:58,320 and I've met him fairly recently. 381 00:24:58,320 --> 00:24:59,815 I know he's still active, but he's 382 00:24:59,815 --> 00:25:02,740 doing most of his experimental work on rats now. 383 00:25:05,600 --> 00:25:11,830 But he discovered, for example, that in dyslexic males who 384 00:25:11,830 --> 00:25:17,060 died, it was very common to find abnormalities 385 00:25:17,060 --> 00:25:20,140 in the left hemisphere, little collections of cells that 386 00:25:20,140 --> 00:25:23,330 appeared not to have migrated normally. 387 00:25:23,330 --> 00:25:31,725 He found-- not in normal males, but in severely dyslexic males. 388 00:25:39,220 --> 00:25:43,940 And we think that because of the hormonal differences 389 00:25:43,940 --> 00:25:46,485 between males and females during development, 390 00:25:46,485 --> 00:25:47,795 that happens more in males. 391 00:25:47,795 --> 00:25:52,250 You don't get it as much in females. 392 00:25:52,250 --> 00:25:55,820 And then I just note here there are brain size differences that 393 00:25:55,820 --> 00:25:58,920 are not dependent on body size. 394 00:25:58,920 --> 00:26:02,610 Male brains being larger from early in development. 395 00:26:02,610 --> 00:26:08,080 I thought at first it had to do simply with body structures 396 00:26:08,080 --> 00:26:14,635 in females who don't-- are not related to brain size 397 00:26:14,635 --> 00:26:16,560 and innervation patterns at all. 398 00:26:16,560 --> 00:26:20,610 But in fact it seems that these-- the differences appear, 399 00:26:20,610 --> 00:26:22,780 according to the imaging work, anyway, 400 00:26:22,780 --> 00:26:24,860 most recent ones I could find indicate 401 00:26:24,860 --> 00:26:27,445 that there's little change after about age five. 402 00:26:30,150 --> 00:26:33,480 I expected it would occur more after sexual maturity, 403 00:26:33,480 --> 00:26:35,820 but that's not the case. 404 00:26:35,820 --> 00:26:37,990 So that's a difference we don't fully understand. 405 00:26:51,990 --> 00:26:54,160 How many of you have heard of Fernando Nottebohm? 406 00:26:57,930 --> 00:26:59,572 AUDIENCE: [INAUDIBLE]. 407 00:26:59,572 --> 00:27:00,280 PROFESSOR: Sorry? 408 00:27:00,280 --> 00:27:02,395 AUDIENCE: Before or after reading the chapter? 409 00:27:02,395 --> 00:27:03,345 PROFESSOR: Oh. 410 00:27:03,345 --> 00:27:05,470 No, I want to know if you knew about him before you 411 00:27:05,470 --> 00:27:06,761 encountered him in the chapter. 412 00:27:09,420 --> 00:27:12,680 At least for the older neuroscientist, 413 00:27:12,680 --> 00:27:16,040 he's very well known, because the findings 414 00:27:16,040 --> 00:27:19,140 made such a big splash when they came out. 415 00:27:19,140 --> 00:27:21,140 And it's led to a lot of the work 416 00:27:21,140 --> 00:27:30,480 using birds as models of plasticity, behavioral change, 417 00:27:30,480 --> 00:27:33,510 and because of its relation to language. 418 00:27:33,510 --> 00:27:38,650 There are a number of parallels in the way human language is 419 00:27:38,650 --> 00:27:43,240 controlled [INAUDIBLE] with singing birds and the way bird 420 00:27:43,240 --> 00:27:45,106 song is controlled. 421 00:27:45,106 --> 00:27:48,590 There were a couple of major findings of that lab. 422 00:27:48,590 --> 00:27:50,030 This is one of the pictures. 423 00:27:52,770 --> 00:27:58,790 I think this one's in the book, where there's-- shows sections 424 00:27:58,790 --> 00:28:03,400 just from the left hemisphere and there are big hemispheric 425 00:28:03,400 --> 00:28:04,690 differences. 426 00:28:04,690 --> 00:28:07,880 They have left hemisphere dominance for bird song, 427 00:28:07,880 --> 00:28:09,640 just like we have left hemisphere 428 00:28:09,640 --> 00:28:12,310 dominance for language. 429 00:28:12,310 --> 00:28:15,400 So this is from the left hemisphere of a canary brain. 430 00:28:15,400 --> 00:28:18,910 The male on the left here and the female on the right. 431 00:28:18,910 --> 00:28:22,210 See that-- the very big difference in that nucleus. 432 00:28:26,800 --> 00:28:28,910 It's pretty easy to quantify. 433 00:28:28,910 --> 00:28:31,030 And then the same here for zebra finches 434 00:28:31,030 --> 00:28:37,480 where it stands out even more. 435 00:28:37,480 --> 00:28:38,920 But again, very big difference. 436 00:28:38,920 --> 00:28:41,400 And you'd find the differences in numbers as well as 437 00:28:41,400 --> 00:28:44,350 in the size of this particular cell group. 438 00:28:44,350 --> 00:28:47,800 This is the nucleus robustus, or robust nucleus 439 00:28:47,800 --> 00:28:49,540 of the acropallium. 440 00:28:49,540 --> 00:28:53,540 It appears to become homologous to the amygdala 441 00:28:53,540 --> 00:28:56,264 or part of the amygdala in mammals. 442 00:28:56,264 --> 00:28:57,180 AUDIENCE: [INAUDIBLE]. 443 00:29:00,120 --> 00:29:01,173 PROFESSOR: Sorry? 444 00:29:01,173 --> 00:29:03,672 AUDIENCE: Is there a reason why the [INAUDIBLE] looks like-- 445 00:29:03,672 --> 00:29:06,560 I know you said that it's not that there's difference 446 00:29:06,560 --> 00:29:09,465 in the number of cells, but is there a reason, 447 00:29:09,465 --> 00:29:11,202 even though it's smaller in the female, 448 00:29:11,202 --> 00:29:15,380 the cell population looks denser than it does in the-- 449 00:29:15,380 --> 00:29:16,300 PROFESSOR: Yeah. 450 00:29:16,300 --> 00:29:19,370 There are still a lot of questions about the females. 451 00:29:19,370 --> 00:29:23,470 Of course, they've concentrated on the males, the singing 452 00:29:23,470 --> 00:29:27,120 species, but I'll mention some of the things 453 00:29:27,120 --> 00:29:32,200 where they find, for example, the cycles of these cell 454 00:29:32,200 --> 00:29:33,100 numbers. 455 00:29:33,100 --> 00:29:36,620 It doesn't affect just this nucleus, but other areas, too. 456 00:29:36,620 --> 00:29:40,510 And it occurs a lot in females as well as males. 457 00:29:40,510 --> 00:29:44,350 And they don't-- it's not as well studied. 458 00:29:44,350 --> 00:29:49,910 But, of course, in evolution, what's 459 00:29:49,910 --> 00:29:52,555 the sex that's orchestrating the whole thing? 460 00:29:52,555 --> 00:29:55,460 It's, of course, the females, because they are choosing males 461 00:29:55,460 --> 00:29:56,840 according to their singing. 462 00:29:56,840 --> 00:29:59,350 So they have to be able to perceive 463 00:29:59,350 --> 00:30:03,040 the details of bird song. 464 00:30:03,040 --> 00:30:05,975 So what we need is more studies of details 465 00:30:05,975 --> 00:30:08,410 of the auditory system and auditory 466 00:30:08,410 --> 00:30:11,450 perception in the females. 467 00:30:11,450 --> 00:30:12,830 OK. 468 00:30:12,830 --> 00:30:15,455 This is one of the Scientific American figures 469 00:30:15,455 --> 00:30:20,470 that Fernando Nottebohm published back in '89. 470 00:30:20,470 --> 00:30:25,080 He shows here a drawing of a syrinx-- 471 00:30:25,080 --> 00:30:26,555 like the vocal cords of the bird. 472 00:30:30,000 --> 00:30:35,950 And the major brain pathways, the higher vocal center 473 00:30:35,950 --> 00:30:36,450 is here. 474 00:30:39,940 --> 00:30:42,940 The diagram here makes it a little easier to see. 475 00:30:46,420 --> 00:30:49,150 It doesn't show the auditory pathway, 476 00:30:49,150 --> 00:30:51,760 but it shows field L, which is the equivalent 477 00:30:51,760 --> 00:30:56,850 of the auditory cortex of the bird. 478 00:30:56,850 --> 00:31:00,770 The thalamic nucleus gets the auditory input 479 00:31:00,770 --> 00:31:05,720 from the caudal midbrain. 480 00:31:05,720 --> 00:31:10,310 The equivalent of the inferior colliculus in the bird projects 481 00:31:10,310 --> 00:31:13,690 field L. It's got three main layers. 482 00:31:13,690 --> 00:31:20,835 And that nucleus projects to this area, and the mesopallium. 483 00:31:20,835 --> 00:31:25,290 The higher vocal center, often just called HPC, 484 00:31:25,290 --> 00:31:27,360 it's sexually dimorphic. 485 00:31:27,360 --> 00:31:30,640 As is nucleus robustus here on the output side. 486 00:31:30,640 --> 00:31:33,310 It gets output directly from the higher vocal center. 487 00:31:33,310 --> 00:31:37,480 The nerve pathways, then, that descend either directly 488 00:31:37,480 --> 00:31:40,975 to the hypoglossal nucleus, which enervates the syrinx. 489 00:31:44,550 --> 00:31:47,665 Particularly a particular part of the hypoglossal nucleus 490 00:31:47,665 --> 00:31:48,460 does that. 491 00:31:48,460 --> 00:31:50,640 But also there's a less direct pathway 492 00:31:50,640 --> 00:31:56,020 through the most intercollicular nucleus. 493 00:31:56,020 --> 00:32:02,170 This is basically the bird's inferior colliculus area. 494 00:32:02,170 --> 00:32:03,720 It doesn't look like a little hill, 495 00:32:03,720 --> 00:32:08,260 so they don't-- we don't call it the inferior colliculus very 496 00:32:08,260 --> 00:32:10,510 much. 497 00:32:10,510 --> 00:32:15,840 But some of the terms are still used, the mammalian terms. 498 00:32:15,840 --> 00:32:19,050 OK, well there's also a less direct and even more 499 00:32:19,050 --> 00:32:20,730 interesting pathway, and it's the one 500 00:32:20,730 --> 00:32:23,805 that's involved most in learning of singing. 501 00:32:27,200 --> 00:32:29,600 These are the two sections, dimorphic structures, 502 00:32:29,600 --> 00:32:31,480 we talked about. 503 00:32:31,480 --> 00:32:33,990 But there's another sexually dimorphic nucleus 504 00:32:33,990 --> 00:32:36,090 here in the striatum just called Area 505 00:32:36,090 --> 00:32:40,080 X. It gets the projection from the higher vocal center, 506 00:32:40,080 --> 00:32:43,320 which, remember, also projects directly 507 00:32:43,320 --> 00:32:45,602 to the nucleus robustus. 508 00:32:45,602 --> 00:32:46,810 They leave that one out here. 509 00:32:46,810 --> 00:32:48,620 There just showing the less direct pathway. 510 00:32:48,620 --> 00:32:53,570 It goes to the striatal area here, which, as in mammals, 511 00:32:53,570 --> 00:33:00,310 the striatum has a pathway through its output neurons 512 00:33:00,310 --> 00:33:02,100 to the thalamus. 513 00:33:02,100 --> 00:33:06,540 And the thalamic structure it goes to projects 514 00:33:06,540 --> 00:33:08,740 to a kind of motor cortical area. 515 00:33:12,190 --> 00:33:15,296 It's called LMAN. 516 00:33:15,296 --> 00:33:18,310 It's the lateral magnocellular nucleus 517 00:33:18,310 --> 00:33:20,600 of the anterior nidopallium. 518 00:33:20,600 --> 00:33:23,620 The nidopallium is that area this 519 00:33:23,620 --> 00:33:27,282 is the neocortical equivalent, but it's subpallial. 520 00:33:27,282 --> 00:33:33,540 The neurons don't migrate the same in birds and in mammals. 521 00:33:33,540 --> 00:33:35,240 But it is equivalent. 522 00:33:35,240 --> 00:33:39,490 So that would be most like the motor cortex, like [INAUDIBLE]. 523 00:33:39,490 --> 00:33:48,440 And it has outputs to the nucleus robustus, which then, 524 00:33:48,440 --> 00:33:50,980 as these two pathways reach in the hypoglossal nucleus. 525 00:33:56,300 --> 00:34:00,970 And that we know, that lesions in these structures 526 00:34:00,970 --> 00:34:04,280 can-- basically, the bigger the lesion, 527 00:34:04,280 --> 00:34:08,137 the more syllables the bird loses through his singing. 528 00:34:08,137 --> 00:34:09,595 Very dependent on those structures. 529 00:34:09,595 --> 00:34:12,695 It's a kind of-- you can say it's a kind of habit learning. 530 00:34:12,695 --> 00:34:16,370 It's a striatal type of learning. 531 00:34:16,370 --> 00:34:19,010 And I'm sure much of our speech is just like that. 532 00:34:22,370 --> 00:34:26,489 So in one of the papers Nottebohm 533 00:34:26,489 --> 00:34:30,080 wrote was called "A Brain for All Seasons," 534 00:34:30,080 --> 00:34:35,730 because these morphological differences in these structures 535 00:34:35,730 --> 00:34:39,630 vary from season to season. 536 00:34:39,630 --> 00:34:45,904 And as does-- as do the levels of the male hormone. 537 00:34:50,040 --> 00:35:04,410 And here, they're plotting, basically, 538 00:35:04,410 --> 00:35:08,990 the syllables that the animal and the volume of these two 539 00:35:08,990 --> 00:35:13,600 structures, the higher vocal center and nucleus robustus. 540 00:35:13,600 --> 00:35:16,285 Now, this, of course, when the bird's very young, 541 00:35:16,285 --> 00:35:20,210 the hormone levels haven't appeared yet-- 542 00:35:20,210 --> 00:35:21,520 hormone differences. 543 00:35:21,520 --> 00:35:24,450 But when they do, you get the growth of these structures. 544 00:35:27,070 --> 00:35:29,700 And it's during this period when you 545 00:35:29,700 --> 00:35:33,880 see the rise in the size of these structures 546 00:35:33,880 --> 00:35:38,130 that the bird is learning the syllables of this song 547 00:35:38,130 --> 00:35:40,880 by listening, basically, to his father. 548 00:35:40,880 --> 00:35:44,020 And it reaches a peak. 549 00:35:44,020 --> 00:35:46,980 And then it doesn't change during the period 550 00:35:46,980 --> 00:35:49,430 when the song is not changing. 551 00:35:49,430 --> 00:35:51,640 So it's no longer plastic. 552 00:35:51,640 --> 00:35:58,820 And then when you enter a period of plastic song again, 553 00:35:58,820 --> 00:36:02,830 the size of these structures goes way down again. 554 00:36:02,830 --> 00:36:05,930 So they're largest when the song is stable-- 555 00:36:05,930 --> 00:36:08,880 when the animal has learned the songs, 556 00:36:08,880 --> 00:36:12,830 and he's using those structures to control his singing. 557 00:36:12,830 --> 00:36:16,310 And this is another way it's been studied, where they've 558 00:36:16,310 --> 00:36:19,580 plotted the changing levels of testosterone 559 00:36:19,580 --> 00:36:21,850 and then the number of syllables. 560 00:36:21,850 --> 00:36:26,770 See them increasing during the period of plastic song. 561 00:36:26,770 --> 00:36:32,980 And then as testosterone levels rise again here, 562 00:36:32,980 --> 00:36:47,960 he loses the-- he loses-- no new syllables appearing, 563 00:36:47,960 --> 00:36:50,680 and the cycle repeats. 564 00:36:50,680 --> 00:36:53,730 The cycle you see here, this is from May to May. 565 00:36:53,730 --> 00:36:58,210 So that's a full year, and that cycle is repeated. 566 00:36:58,210 --> 00:37:02,470 But then the other big discovery was 567 00:37:02,470 --> 00:37:07,040 birth of neurons that migrate just like in development. 568 00:37:07,040 --> 00:37:10,400 Here, you see migrating neurons here, 569 00:37:10,400 --> 00:37:15,050 where they're showing wheel processes stained 570 00:37:15,050 --> 00:37:20,580 with the [INAUDIBLE] protein and then neurons moving along them. 571 00:37:20,580 --> 00:37:25,730 And this is from a tritiaed thymadine study 572 00:37:25,730 --> 00:37:27,980 from a Scientific American article. 573 00:37:27,980 --> 00:37:30,380 It has particularly nice illustrations, 574 00:37:30,380 --> 00:37:36,090 and here he shows you inject the thymadine, 575 00:37:36,090 --> 00:37:38,670 so you label the dividing cells. 576 00:37:38,670 --> 00:37:41,890 If you look at the brain just one day later, 577 00:37:41,890 --> 00:37:43,720 you see where you'd expect them. 578 00:37:43,720 --> 00:37:48,786 They're all-- you've labeled the cells in the ventricular layer. 579 00:37:48,786 --> 00:37:51,190 Now, remember, these aren't babies anymore. 580 00:37:51,190 --> 00:37:54,600 This isn't when the brain first formed. 581 00:37:54,600 --> 00:37:58,450 And this is happening every season. 582 00:37:58,450 --> 00:38:00,100 Look at them after eight days. 583 00:38:00,100 --> 00:38:01,850 They're beginning to migrate. 584 00:38:01,850 --> 00:38:06,195 After 15 days, they've moved out into much of the endbrain. 585 00:38:09,700 --> 00:38:15,540 At 40 days, they've not only moved well away from where they 586 00:38:15,540 --> 00:38:20,250 were born here at the ventricle, but they're-- the ones shown 587 00:38:20,250 --> 00:38:24,750 in red are differentiating into neurons. 588 00:38:24,750 --> 00:38:28,690 And as I said, this is actually-- the total emphasise 589 00:38:28,690 --> 00:38:30,380 was on males at the beginning. 590 00:38:30,380 --> 00:38:32,750 But it turns out there's quite a bit of cell birth 591 00:38:32,750 --> 00:38:36,345 like this in the female, too. 592 00:38:36,345 --> 00:38:39,030 And even though we know that, it's 593 00:38:39,030 --> 00:38:45,160 simply not been studied as much because we can't correlated it 594 00:38:45,160 --> 00:38:46,920 with the singing. 595 00:38:46,920 --> 00:38:48,840 The female isn't doing much singing. 596 00:38:56,560 --> 00:38:59,050 So a couple of things that indicate that there's a lot 597 00:38:59,050 --> 00:39:03,080 of sex differences that we probably haven't even found 598 00:39:03,080 --> 00:39:11,940 yet, and certainly haven't-- one is that if you look at most 599 00:39:11,940 --> 00:39:15,200 of this was in vitro work. 600 00:39:15,200 --> 00:39:19,510 Look at the differentiation of the midbrain dopamine neurons 601 00:39:19,510 --> 00:39:23,170 that's affected by sex steriods in culture. 602 00:39:23,170 --> 00:39:25,790 And she found an interaction between the estrogens 603 00:39:25,790 --> 00:39:26,665 and [INAUDIBLE]. 604 00:39:26,665 --> 00:39:30,260 They're affecting the growth hormones directly. 605 00:39:30,260 --> 00:39:33,660 So in fact, there's hormone-- sex hormone receptors 606 00:39:33,660 --> 00:39:36,170 in many parts of the brain, including 607 00:39:36,170 --> 00:39:42,930 many areas that we've not seen nuclear structural dimorphism, 608 00:39:42,930 --> 00:39:45,390 but that doesn't mean the neurons aren't being 609 00:39:45,390 --> 00:39:49,550 affected, even though they may not change in the growth 610 00:39:49,550 --> 00:39:52,010 structures that we look at more anatomically. 611 00:39:55,080 --> 00:39:57,470 So what in addition to hormonal factors 612 00:39:57,470 --> 00:40:01,110 may explain male/female differences? 613 00:40:01,110 --> 00:40:03,260 Is it only hormones that we need to look at? 614 00:40:03,260 --> 00:40:05,790 And that is all people thought they 615 00:40:05,790 --> 00:40:08,130 had to look at for many years. 616 00:40:08,130 --> 00:40:14,790 They assumed that brains of males and females are similar. 617 00:40:14,790 --> 00:40:17,522 They're basically all female, and then 618 00:40:17,522 --> 00:40:22,240 the male brains differentiate because of testosterone. 619 00:40:22,240 --> 00:40:25,900 And if you remove the gonads of a male, 620 00:40:25,900 --> 00:40:28,610 then the brain just stays female. 621 00:40:28,610 --> 00:40:32,580 And that was the picture that everybody learned. 622 00:40:32,580 --> 00:40:37,650 And then gene expression studies came on, 623 00:40:37,650 --> 00:40:43,420 and this fellow, Eric Vilain, out at UCLA 624 00:40:43,420 --> 00:40:48,850 started publishing his results on gene expression studies. 625 00:40:48,850 --> 00:40:53,450 And they were doing-- they could compare 626 00:40:53,450 --> 00:40:56,200 the expression of over 12,000 genes 627 00:40:56,200 --> 00:40:58,710 with their screening method, comparing 628 00:40:58,710 --> 00:41:02,080 male and female brains using embryonic mice. 629 00:41:02,080 --> 00:41:06,430 And they started long before the animal developed sex organs. 630 00:41:06,430 --> 00:41:11,310 And they found that 54 genes were expressed 631 00:41:11,310 --> 00:41:15,480 in different amounts in male and female mouse brains prior 632 00:41:15,480 --> 00:41:18,910 to any hormones influence. 633 00:41:18,910 --> 00:41:23,350 And 18 of them were expressed at higher levels in male brains. 634 00:41:23,350 --> 00:41:27,370 36 were expressed at higher levels in the female brain. 635 00:41:27,370 --> 00:41:31,325 That was published back in 2003. 636 00:41:31,325 --> 00:41:31,825 Yes? 637 00:41:31,825 --> 00:41:32,741 AUDIENCE: [INAUDIBLE]. 638 00:41:36,520 --> 00:41:37,690 PROFESSOR: No. 639 00:41:37,690 --> 00:41:43,680 No, they're not all-- the differences 640 00:41:43,680 --> 00:41:45,670 appear-- I'm not sure. 641 00:41:45,670 --> 00:41:49,750 You could look here in these papers 642 00:41:49,750 --> 00:41:54,960 to see if they tried to be more specific. 643 00:41:54,960 --> 00:41:58,050 But you see, when they first discovered these, 644 00:41:58,050 --> 00:42:02,450 they didn't even know what proteins 645 00:42:02,450 --> 00:42:06,280 these things are coding for, and they-- it 646 00:42:06,280 --> 00:42:09,570 was this large scale screening that they were using. 647 00:42:09,570 --> 00:42:11,390 But that's just the first step in trying 648 00:42:11,390 --> 00:42:15,450 to understand what's going on. 649 00:42:15,450 --> 00:42:19,530 In 1990, they did identify one on the Y chromosome. 650 00:42:19,530 --> 00:42:22,510 They call it SRY. 651 00:42:22,510 --> 00:42:26,550 It's a sex determining region on the Y chromosome. 652 00:42:26,550 --> 00:42:29,025 It's also known as the testis determining gene. 653 00:42:31,860 --> 00:42:36,700 That same gene is found being expressed 654 00:42:36,700 --> 00:42:39,450 in the substantia nigra in rats. 655 00:42:39,450 --> 00:42:43,300 It's involved in dopamine secretion. 656 00:42:43,300 --> 00:42:47,680 In fact, if you reduce the gene's activity, 657 00:42:47,680 --> 00:42:51,800 you get a Parkinson's-like syndrome, 658 00:42:51,800 --> 00:42:58,990 which is interesting because it could explain why men are more 659 00:42:58,990 --> 00:43:01,840 susceptible to Parkinson's disease than women, 660 00:43:01,840 --> 00:43:03,530 but still women get it. 661 00:43:03,530 --> 00:43:09,160 And women produced plenty of dopamine 662 00:43:09,160 --> 00:43:10,874 even if they're not expressing that gene. 663 00:43:10,874 --> 00:43:12,665 So obviously, there are other determinants. 664 00:43:15,260 --> 00:43:17,880 So that's-- 665 00:43:17,880 --> 00:43:22,490 And here is the problem-- I just wanted to note here, 666 00:43:22,490 --> 00:43:28,620 it's a disturbing part of modern molecular-- cell molecular work 667 00:43:28,620 --> 00:43:31,700 that often, you hear about something this early 668 00:43:31,700 --> 00:43:33,640 and then you stop learning about it. 669 00:43:33,640 --> 00:43:35,751 The reason is people delay their publication 670 00:43:35,751 --> 00:43:37,375 because they want to patent everything. 671 00:43:44,010 --> 00:43:47,410 People get greedy, and the drug companies 672 00:43:47,410 --> 00:43:50,410 are often dominating the game. 673 00:43:50,410 --> 00:43:52,740 So I think we would know a lot more now if this 674 00:43:52,740 --> 00:43:56,200 weren't-- people weren't so convinced they were going 675 00:43:56,200 --> 00:43:57,800 to make a lot of money from it. 676 00:43:57,800 --> 00:43:58,594 Sorry to say. 677 00:43:58,594 --> 00:43:59,510 AUDIENCE: [INAUDIBLE]. 678 00:44:02,180 --> 00:44:04,160 PROFESSOR: Well, you can't-- basically, 679 00:44:04,160 --> 00:44:07,240 they won't publish it until they're sure that 680 00:44:07,240 --> 00:44:11,486 they've patented everything or initiated the patent. 681 00:44:11,486 --> 00:44:13,110 There's a whole procedure that follows. 682 00:44:13,110 --> 00:44:15,720 Then yes, you can publish, but if you publish too early, 683 00:44:15,720 --> 00:44:19,180 then everybody else will get started on it, 684 00:44:19,180 --> 00:44:21,070 and maybe they can work faster than you. 685 00:44:21,070 --> 00:44:23,207 So people just delay. 686 00:44:23,207 --> 00:44:24,040 They keep it secret. 687 00:44:27,590 --> 00:44:29,640 It's true even in the field I was 688 00:44:29,640 --> 00:44:32,990 working in for so long, the regeneration work. 689 00:44:32,990 --> 00:44:34,760 Again, people are so convinced they've 690 00:44:34,760 --> 00:44:37,160 got some big finding that's going to make a lot of money. 691 00:44:39,751 --> 00:44:40,250 All right. 692 00:44:42,970 --> 00:44:45,470 I don't claim to be lily white either, 693 00:44:45,470 --> 00:44:47,970 because I got involved in that for a little while, 694 00:44:47,970 --> 00:44:50,280 but then I stopped. 695 00:44:50,280 --> 00:44:53,760 I decided it was destroying the way I did science. 696 00:44:53,760 --> 00:44:55,260 I didn't want it anymore. 697 00:45:00,180 --> 00:45:02,760 Some of the differences in sexual orientation 698 00:45:02,760 --> 00:45:05,090 might be explained in gene expression differences. 699 00:45:10,430 --> 00:45:13,300 They found in mothers of homosexual men, 700 00:45:13,300 --> 00:45:17,213 there's some skewing of X chromosome inactivation. 701 00:45:21,300 --> 00:45:23,590 But it would only explain results 702 00:45:23,590 --> 00:45:29,660 for only a subgroup of gay men, and it's even 703 00:45:29,660 --> 00:45:32,490 been reported that such skewing is not 704 00:45:32,490 --> 00:45:34,820 transmitted to the offspring. 705 00:45:34,820 --> 00:45:36,980 So that's been up in the air. 706 00:45:40,760 --> 00:45:43,470 Perhaps the-- and you can look under Vilain, 707 00:45:43,470 --> 00:45:45,120 you'll see the more recent things 708 00:45:45,120 --> 00:45:47,300 that he's been publishing. 709 00:45:47,300 --> 00:45:49,410 And this is Dean Hammer of the NIH, 710 00:45:49,410 --> 00:45:53,986 by the way, who first discovered the genetic differences in-- 711 00:45:53,986 --> 00:45:54,902 AUDIENCE: [INAUDIBLE]. 712 00:45:58,805 --> 00:46:00,180 PROFESSOR: Well, the X chromosome 713 00:46:00,180 --> 00:46:05,360 is inactivated in-- during normal development. 714 00:46:05,360 --> 00:46:11,070 And this skewing can vary a lot in how asymmetric it is. 715 00:46:11,070 --> 00:46:14,070 That's where there was an abnormal, 716 00:46:14,070 --> 00:46:18,320 they claim, to get this extreme skewing 717 00:46:18,320 --> 00:46:21,160 in mothers of homosexual man. 718 00:46:21,160 --> 00:46:26,220 But I report the finding here in case some of you 719 00:46:26,220 --> 00:46:28,510 may want to see what's happened to it. 720 00:46:28,510 --> 00:46:30,280 And I didn't follow it up this year. 721 00:46:30,280 --> 00:46:31,472 I didn't look any further. 722 00:46:31,472 --> 00:46:33,430 I was looking at a lot of other things instead. 723 00:46:37,340 --> 00:46:40,760 And I don't think I put this in the book. 724 00:46:40,760 --> 00:46:46,110 If I had, I would've done a lot more looking at it. 725 00:46:46,110 --> 00:46:49,800 There's a lot of other quantitative variations 726 00:46:49,800 --> 00:46:53,365 in human brains, including sex differences. 727 00:46:56,720 --> 00:46:59,785 And they've been found to have both genetic and environmental 728 00:46:59,785 --> 00:47:00,285 origins. 729 00:47:02,950 --> 00:47:06,400 They vary a lot from one part of the brain to another. 730 00:47:06,400 --> 00:47:08,140 For example, the cerebellum seems 731 00:47:08,140 --> 00:47:10,970 to show a lot of variation, and they 732 00:47:10,970 --> 00:47:13,610 think it shows more variation than other structures 733 00:47:13,610 --> 00:47:19,590 because experiential factors make a big difference. 734 00:47:19,590 --> 00:47:23,410 That was Rapaport's suggestion. 735 00:47:23,410 --> 00:47:25,660 She's given a lot of talks on this. 736 00:47:25,660 --> 00:47:29,990 She's given one talk here, but not recently. 737 00:47:29,990 --> 00:47:32,650 She had very large numbers in her studies, 738 00:47:32,650 --> 00:47:36,499 so we think it's pretty reliable, a lot of the things 739 00:47:36,499 --> 00:47:37,165 she's reporting. 740 00:47:41,090 --> 00:47:43,140 They find differences between-- this 741 00:47:43,140 --> 00:47:45,550 has been known for a very long time. 742 00:47:45,550 --> 00:47:47,620 There's all kinds of studies in differences 743 00:47:47,620 --> 00:47:52,200 between schizophrenic brains and normal brains. 744 00:47:52,200 --> 00:47:54,640 But in fact, they're quite variable. 745 00:47:54,640 --> 00:47:59,535 And there's so many studies of schizophrenia 746 00:47:59,535 --> 00:48:03,300 that indicate this, that, and the other kind of thing that 747 00:48:03,300 --> 00:48:06,320 explains what schizophrenia is that you begin to realize 748 00:48:06,320 --> 00:48:08,810 after a while that it's because there is no explanation. 749 00:48:08,810 --> 00:48:11,640 There's just a lot of variation. 750 00:48:11,640 --> 00:48:15,530 So we don't want to have a final answer 751 00:48:15,530 --> 00:48:21,120 there, except perhaps for certain schizophrenics. 752 00:48:24,610 --> 00:48:28,840 But one thing that really surprised people was this. 753 00:48:28,840 --> 00:48:34,010 Young people with attention deficit hyperactivity disorder, 754 00:48:34,010 --> 00:48:37,530 they find region-specific differences 755 00:48:37,530 --> 00:48:39,940 between people without it and people with it. 756 00:48:39,940 --> 00:48:43,590 And of course it varies with severity as well. 757 00:48:43,590 --> 00:48:47,930 So the fact is, there's a lot of individual differences 758 00:48:47,930 --> 00:48:52,110 in brains, and some of it-- the fact that it's correlated, 759 00:48:52,110 --> 00:48:56,265 remember, doesn't prove anything about cause. 760 00:48:56,265 --> 00:48:58,550 It only makes a suggestion that it 761 00:48:58,550 --> 00:49:02,640 may be related to the causes. 762 00:49:02,640 --> 00:49:07,950 Don't be too quick too-- things appear in the newspapers 763 00:49:07,950 --> 00:49:12,550 all the time, usually published by medical residents who 764 00:49:12,550 --> 00:49:15,881 find some correlation or other and they publish it. 765 00:49:15,881 --> 00:49:18,380 There's a lot of pressure to publish in medicine when you're 766 00:49:18,380 --> 00:49:21,835 early in your career because you get better jobs if you're 767 00:49:21,835 --> 00:49:23,160 published. 768 00:49:23,160 --> 00:49:28,550 But people go too far in interpreting correlations. 769 00:49:28,550 --> 00:49:30,280 In other words, there's no experiment 770 00:49:30,280 --> 00:49:33,535 done to prove any causative relationship. 771 00:49:36,590 --> 00:49:38,800 So I just-- these are the kinds of things 772 00:49:38,800 --> 00:49:40,680 you should review here. 773 00:49:40,680 --> 00:49:43,890 And if you like Rumi, there's one of his poems. 774 00:49:49,970 --> 00:49:51,660 I think we're at the end of the hour. 775 00:49:51,660 --> 00:49:56,390 So we'll be talking now about the hippocampal formation 776 00:49:56,390 --> 00:49:57,512 next time. 777 00:49:57,512 --> 00:49:59,970 And then finally, we'll say a few things about the amygdala 778 00:49:59,970 --> 00:50:04,140 and ventral striatum before we go on to the dorsal stream. 779 00:50:04,140 --> 00:50:05,690 striatum.