1 00:00:00,250 --> 00:00:01,800 The following content is provided 2 00:00:01,800 --> 00:00:04,040 under a Creative Commons license. 3 00:00:04,040 --> 00:00:06,890 Your support will help MIT OpenCourseWare continue 4 00:00:06,890 --> 00:00:10,740 to offer high quality educational resources for free. 5 00:00:10,740 --> 00:00:13,360 To make a donation or view additional materials 6 00:00:13,360 --> 00:00:17,241 from hundreds of MIT courses, visit MIT OpenCourseWare 7 00:00:17,241 --> 00:00:17,866 at ocw.mit.edu. 8 00:00:22,960 --> 00:00:24,550 PROFESSOR: We're going to spend most 9 00:00:24,550 --> 00:00:26,300 of the time on the corpus striatum today, 10 00:00:26,300 --> 00:00:30,246 but I want to finish the other major part 11 00:00:30,246 --> 00:00:33,920 of the basal ganglia, the amygdala, which 12 00:00:33,920 --> 00:00:35,920 is closely connected to the basal forebrain. 13 00:00:35,920 --> 00:00:40,540 So let's define the basal forebrain. 14 00:00:44,430 --> 00:00:48,240 In discussions of aging in human pathologies, 15 00:00:48,240 --> 00:00:52,010 you always hear about the basal forebrain, 16 00:00:52,010 --> 00:00:57,280 because of the degeneration of acetylcholine containing 17 00:00:57,280 --> 00:01:01,835 neurons in the basal nucleus, located there. 18 00:01:01,835 --> 00:01:03,545 And that'll be in the pictures. 19 00:01:06,380 --> 00:01:10,850 So let's look at the medial view of the cerebral hemisphere 20 00:01:10,850 --> 00:01:12,860 in a rodent. 21 00:01:12,860 --> 00:01:18,610 And this is the hemisphere. 22 00:01:18,610 --> 00:01:21,940 This is the brain stem. 23 00:01:21,940 --> 00:01:24,750 And I just cut off the hypothalamus here 24 00:01:24,750 --> 00:01:26,060 and included it here. 25 00:01:26,060 --> 00:01:28,690 Because, remember, in the basal forebrain 26 00:01:28,690 --> 00:01:30,905 the hemispheres are joined at the bottom. 27 00:01:34,210 --> 00:01:38,326 So to get the hemispheres separated from the brain 28 00:01:38,326 --> 00:01:43,970 stem we have to cut through the basal forebrain. 29 00:01:43,970 --> 00:01:47,830 And I've cut it right along the midline here. 30 00:01:47,830 --> 00:01:53,680 And I've indicated basal forebrain structures here. 31 00:01:53,680 --> 00:01:55,520 Includes a collection of structures, 32 00:01:55,520 --> 00:01:58,600 including the olfactory tubercle right at the base. 33 00:01:58,600 --> 00:02:02,230 You see it in the sections. 34 00:02:02,230 --> 00:02:04,550 See, here we're in the hypothalamus. 35 00:02:04,550 --> 00:02:08,120 There's the amygdala in the hemisphere. 36 00:02:08,120 --> 00:02:10,320 This is in front of the optic chiasm. 37 00:02:10,320 --> 00:02:15,800 And there you see all the major basal forebrain structures, 38 00:02:15,800 --> 00:02:18,430 plus the septum. 39 00:02:18,430 --> 00:02:20,280 We usually don't include the septum 40 00:02:20,280 --> 00:02:22,420 as part of the basal forebrain, but it could be. 41 00:02:22,420 --> 00:02:31,175 Functionally it's very closely allied to these structures 42 00:02:31,175 --> 00:02:32,630 we call basal forebrain. 43 00:02:32,630 --> 00:02:39,140 The other, broader, term is ventral striatum, 44 00:02:39,140 --> 00:02:41,830 which, in recent research, is proved 45 00:02:41,830 --> 00:02:45,130 to be more ventral medial striatum. 46 00:02:45,130 --> 00:02:49,580 And I've indicated that the way I've drawn the color here, 47 00:02:49,580 --> 00:02:57,300 showing that the medial part of the more dorsal striatum 48 00:02:57,300 --> 00:03:00,230 is really part of the limbic striatum. 49 00:03:00,230 --> 00:03:02,060 Maybe limbic striatum is a better term 50 00:03:02,060 --> 00:03:04,770 than ventral striatum now. 51 00:03:04,770 --> 00:03:08,000 But it usually uses ventral striatum in the book, 52 00:03:08,000 --> 00:03:13,510 because that is-- most of the literature calls it that. 53 00:03:13,510 --> 00:03:18,380 So what does it include, besides the olfactory tubercle here? 54 00:03:21,230 --> 00:03:26,530 Well, I indicated two major structures here. 55 00:03:26,530 --> 00:03:30,160 You see the largest one, little further forward here, 56 00:03:30,160 --> 00:03:32,480 the nucleus accumbens. 57 00:03:32,480 --> 00:03:36,360 It's major inputs from the hippocampal formation 58 00:03:36,360 --> 00:03:39,538 and from the amygdala. 59 00:03:39,538 --> 00:03:41,880 But the amygdala primarily projects 60 00:03:41,880 --> 00:03:44,810 to the more caudal one here. 61 00:03:44,810 --> 00:03:46,410 This is where they overlap. 62 00:03:46,410 --> 00:03:48,620 That's the bed nucleus of the stria terminalis, 63 00:03:48,620 --> 00:03:50,010 which we mentioned last time. 64 00:03:50,010 --> 00:03:53,170 And I've indicated in blue there the acetylcholine 65 00:03:53,170 --> 00:03:56,950 containing neurons that you see in the medial septum. 66 00:03:56,950 --> 00:04:03,510 You see them in this diagonal band of cells. 67 00:04:03,510 --> 00:04:05,780 We call it the diagonal band of Broca, 68 00:04:05,780 --> 00:04:08,470 because he named them, that area. 69 00:04:08,470 --> 00:04:11,595 And then the basal nucleus at the bottom here. 70 00:04:11,595 --> 00:04:15,360 And you see the basal nucleus [? they're ?] forward as well. 71 00:04:15,360 --> 00:04:18,540 Those are the cells that have this very widespread projection 72 00:04:18,540 --> 00:04:20,910 to the neocortex. 73 00:04:20,910 --> 00:04:30,040 They project to most if not all of the neocortex. 74 00:04:33,040 --> 00:04:35,410 So it was mentioned in chapter 17 75 00:04:35,410 --> 00:04:39,120 when we were talking about brain states. 76 00:04:39,120 --> 00:04:45,310 OK, now one other topic here, the kind 77 00:04:45,310 --> 00:04:48,700 of abnormal brain connections that we know 78 00:04:48,700 --> 00:04:52,390 occur, at least many types of schizophrenia. 79 00:04:52,390 --> 00:04:58,850 And the types that don't include the abnormal connections 80 00:04:58,850 --> 00:05:02,970 appear to have abnormalities, though, in the receptors, 81 00:05:02,970 --> 00:05:05,280 affecting the same system we're talking about. 82 00:05:14,940 --> 00:05:20,392 I came up with this hypothesis of and early lesion explanation 83 00:05:20,392 --> 00:05:24,100 of some forms of schizophrenia back in the '70s, 84 00:05:24,100 --> 00:05:26,140 based on work in the olfactory system 85 00:05:26,140 --> 00:05:29,000 and visual system that I and other people had done. 86 00:05:35,930 --> 00:05:39,310 It was inspired by a study of people 87 00:05:39,310 --> 00:05:43,110 with temporal lobe epilepsy that had been operated on 88 00:05:43,110 --> 00:05:46,640 in order to get the tissue generating seizures-- 89 00:05:46,640 --> 00:05:49,550 it's a tissue in the temporal lobe-- removed, 90 00:05:49,550 --> 00:05:53,910 to cause the seizures to stop. 91 00:05:53,910 --> 00:05:56,540 And they found that the patients could 92 00:05:56,540 --> 00:05:58,080 be grouped into two types. 93 00:05:58,080 --> 00:06:00,250 After they took the tissue out it 94 00:06:00,250 --> 00:06:04,800 included amygdala and adjoining structures. 95 00:06:07,330 --> 00:06:09,905 They found the signs of early damage. 96 00:06:12,992 --> 00:06:14,700 But they found that they could be grouped 97 00:06:14,700 --> 00:06:23,440 into postnatal lesions that were due to high fever in infancy, 98 00:06:23,440 --> 00:06:26,340 and prenatal lesions, due to what we call 99 00:06:26,340 --> 00:06:29,770 hamartomas, a prenatal tumor. 100 00:06:29,770 --> 00:06:35,700 So that means one group had much earlier lesions. 101 00:06:35,700 --> 00:06:41,790 And I've summarized there at the bottom the real basis 102 00:06:41,790 --> 00:06:46,020 for this idea, other than the fact of early lesions. 103 00:06:46,020 --> 00:06:50,030 And that is that the earlier the lesion in these other systems, 104 00:06:50,030 --> 00:06:52,940 at least, the greater the plasticity, that 105 00:06:52,940 --> 00:06:56,965 is, more sprouting, more chances of regeneration, and so forth. 106 00:06:56,965 --> 00:07:00,140 But here we're talking about sprouting. 107 00:07:00,140 --> 00:07:02,852 So I just wanted to run through the hypotheses. 108 00:07:02,852 --> 00:07:06,410 These are the connections I'm talking about. 109 00:07:06,410 --> 00:07:09,860 In green there I show the very widespread projections 110 00:07:09,860 --> 00:07:14,080 of the catecholamines, the monoamine, serotonin, 111 00:07:14,080 --> 00:07:19,850 and some acetylcholine axons as well. 112 00:07:19,850 --> 00:07:24,300 I was thinking mainly of the catecholamines, dopamine 113 00:07:24,300 --> 00:07:26,570 and norepinephrine. 114 00:07:26,570 --> 00:07:31,620 And I knew at the time I drew up this hypothesis that there were 115 00:07:31,620 --> 00:07:34,660 dopamine abnormalities in the prefrontal cortex 116 00:07:34,660 --> 00:07:38,550 in schizophrenics in many of them. 117 00:07:38,550 --> 00:07:42,095 OK, so here I'm showing how the catecholamine axons have 118 00:07:42,095 --> 00:07:46,300 these very widely branching axons that 119 00:07:46,300 --> 00:07:48,030 go through the amygdala. 120 00:07:48,030 --> 00:07:51,520 They go into the basal forebrain and septal area. 121 00:07:51,520 --> 00:07:53,395 And they go to the prefrontal cortex. 122 00:07:56,090 --> 00:07:59,320 The cortical projections are much more [INAUDIBLE] 123 00:07:59,320 --> 00:08:05,080 these prefrontal areas than they are to other cortical areas. 124 00:08:05,080 --> 00:08:13,090 And according to that study I was just talking about, 125 00:08:13,090 --> 00:08:15,270 both of these groups had amygdala lesions, 126 00:08:15,270 --> 00:08:17,180 but one of them had much earlier lesions. 127 00:08:17,180 --> 00:08:21,382 And I would predict this kind of sprouting. 128 00:08:21,382 --> 00:08:25,770 For one thing, by removing this structure 129 00:08:25,770 --> 00:08:27,720 we've eliminated these projections 130 00:08:27,720 --> 00:08:31,920 to basic forebrain and prefrontal cortexes. 131 00:08:31,920 --> 00:08:34,530 But we've also pruned these axons, 132 00:08:34,530 --> 00:08:37,870 making it likely that they will show compensatory 133 00:08:37,870 --> 00:08:39,980 sprouting in other areas. 134 00:08:39,980 --> 00:08:42,045 So those two factors together indicate 135 00:08:42,045 --> 00:08:44,230 that this kind of sprouting would 136 00:08:44,230 --> 00:08:48,530 be expected in the basal forebrain 137 00:08:48,530 --> 00:08:49,880 and in the prefrontal cortex. 138 00:08:52,620 --> 00:08:57,630 And the question is, OK, what about schizophrenics 139 00:08:57,630 --> 00:08:59,400 and early damage? 140 00:08:59,400 --> 00:09:05,900 The fact is, a number of schizophrenics, particularly 141 00:09:05,900 --> 00:09:09,640 the ones that are the hardest to treat-- they're the ones that 142 00:09:09,640 --> 00:09:15,140 often are in mental hospitals for most of their adult life-- 143 00:09:15,140 --> 00:09:18,050 have enlarged brain ventricles. 144 00:09:18,050 --> 00:09:21,050 Now, of course, with more drugs to treat them, more of them 145 00:09:21,050 --> 00:09:23,180 are not in the mental hospitals. 146 00:09:23,180 --> 00:09:26,750 Because you can alleviate their symptoms 147 00:09:26,750 --> 00:09:29,830 with some of the drugs. 148 00:09:29,830 --> 00:09:34,450 But this just shows schizophrenian monozygotic 149 00:09:34,450 --> 00:09:37,920 twins, where you have one twin with schizophrenia. 150 00:09:37,920 --> 00:09:41,030 The other doesn't have it. 151 00:09:41,030 --> 00:09:45,960 And as they often find in these cases, 152 00:09:45,960 --> 00:09:50,860 the affected twin has larger ventricles. 153 00:09:50,860 --> 00:09:52,380 And we know that larger ventricles 154 00:09:52,380 --> 00:09:56,200 can result from early damage. 155 00:09:56,200 --> 00:09:59,180 And this is from a study where they had a lot of patients 156 00:09:59,180 --> 00:10:02,090 and they looked at the relative size 157 00:10:02,090 --> 00:10:04,615 of the ventricles with respect to the rest of it, 158 00:10:04,615 --> 00:10:07,820 to the whole brain. 159 00:10:07,820 --> 00:10:09,130 And here that is in normals. 160 00:10:09,130 --> 00:10:10,860 And you can see it changes with age. 161 00:10:10,860 --> 00:10:14,276 The ventricles do tend to enlarge after age 40. 162 00:10:14,276 --> 00:10:18,130 This is for males here. 163 00:10:18,130 --> 00:10:21,090 The curves are a little bit different for females. 164 00:10:21,090 --> 00:10:25,145 But it's a very significant finding, 165 00:10:25,145 --> 00:10:30,430 that the schizophrenics have larger ventricles, 166 00:10:30,430 --> 00:10:33,450 an indication of early damage. 167 00:10:33,450 --> 00:10:35,930 Many of them do have this temporal lobe damage. 168 00:10:35,930 --> 00:10:38,397 Now, different studies have indicated, well, 169 00:10:38,397 --> 00:10:43,600 the hippocampus is important, the amygdala's important. 170 00:10:43,600 --> 00:10:44,720 Sometimes they don't know. 171 00:10:44,720 --> 00:10:47,130 But the particular study I'm talking about 172 00:10:47,130 --> 00:10:49,370 was more of a natural experiment. 173 00:10:49,370 --> 00:10:52,960 Because the surgeons had actually removed 174 00:10:52,960 --> 00:10:56,370 the tissue to stop the seizures. 175 00:10:56,370 --> 00:11:01,390 And then they found one group with earlier lesions. 176 00:11:01,390 --> 00:11:05,070 So the question is, then, did any of these people 177 00:11:05,070 --> 00:11:08,080 have schizophrenia. 178 00:11:08,080 --> 00:11:10,530 So they checked for hospital admissions 179 00:11:10,530 --> 00:11:14,450 for schizophrenic type symptomatology. 180 00:11:14,450 --> 00:11:17,610 And they found that the ones with the earlier lesions, 181 00:11:17,610 --> 00:11:20,115 the hamartomas, were much more frequently 182 00:11:20,115 --> 00:11:21,240 admitted for schizophrenia. 183 00:11:21,240 --> 00:11:24,220 It's a fairly high percentage. 184 00:11:24,220 --> 00:11:26,140 Of course, there's always a lot of variability 185 00:11:26,140 --> 00:11:27,712 in the studies like this. 186 00:11:30,540 --> 00:11:32,320 But-- yes? 187 00:11:35,757 --> 00:11:46,474 AUDIENCE: [INAUDIBLE] in like epilepsy in schizophrenics? 188 00:11:46,474 --> 00:11:47,890 PROFESSOR: That's a good question. 189 00:11:47,890 --> 00:11:52,230 You'd like to know if in studies of schizophrenics, 190 00:11:52,230 --> 00:11:54,330 how many of them have epilepsy. 191 00:11:54,330 --> 00:11:56,390 Usually they're kept separate, but I 192 00:11:56,390 --> 00:11:59,726 don't know of studies that have just looked broadly 193 00:11:59,726 --> 00:12:00,702 at schizophrenics. 194 00:12:07,460 --> 00:12:09,830 I actually have seen some of these studies, 195 00:12:09,830 --> 00:12:12,430 but I can't recall at the moment. 196 00:12:12,430 --> 00:12:14,580 It'd be worthwhile checking. 197 00:12:14,580 --> 00:12:18,700 OK, and then just to remind you of the widespread nature 198 00:12:18,700 --> 00:12:20,140 of these projections. 199 00:12:20,140 --> 00:12:23,330 The dopaminergic projections are a little more widespread 200 00:12:23,330 --> 00:12:25,800 according to recent studies than they were in the earlier 201 00:12:25,800 --> 00:12:29,640 studies, where they were seen mainly in the cortex, which 202 00:12:29,640 --> 00:12:31,860 is seen mainly in the prefrontal areas. 203 00:12:31,860 --> 00:12:34,421 Now we know they are also in the more caudal areas, 204 00:12:34,421 --> 00:12:37,510 but just less dense. 205 00:12:37,510 --> 00:12:42,320 But also we know the basal nucleus projections 206 00:12:42,320 --> 00:12:43,680 are shown here. 207 00:12:43,680 --> 00:12:46,020 Very widespread. 208 00:12:46,020 --> 00:12:47,810 They could be affected too. 209 00:12:47,810 --> 00:12:53,190 And note that this is the way they depict the amygdala. 210 00:12:53,190 --> 00:12:59,385 And in every case these four systems 211 00:12:59,385 --> 00:13:01,950 of widespread projections all go to the amygdala 212 00:13:01,950 --> 00:13:05,514 as well as to other parts of the brain. 213 00:13:05,514 --> 00:13:06,410 All right? 214 00:13:06,410 --> 00:13:11,410 And this is just to show you binding to receptors 215 00:13:11,410 --> 00:13:16,580 for these different transmitters of the various anti-psychotic 216 00:13:16,580 --> 00:13:18,430 drugs. 217 00:13:18,430 --> 00:13:24,440 The blue shows the D2 dopamine receptor binding drugs. 218 00:13:24,440 --> 00:13:27,980 And you can see very commonly that these drugs have 219 00:13:27,980 --> 00:13:31,090 a high affinity for those receptors. 220 00:13:31,090 --> 00:13:35,170 But there's an affinity for the receptors for the other type 221 00:13:35,170 --> 00:13:40,410 of dopamine [? receptor. ?] So there's 222 00:13:40,410 --> 00:13:42,501 two kinds of dopamine receptors studied here. 223 00:13:42,501 --> 00:13:44,250 There's two kinds of adrenergic receptors. 224 00:13:46,950 --> 00:13:50,145 Some of them, the binding's higher, especially 225 00:13:50,145 --> 00:13:52,210 for this big group on the right. 226 00:13:57,112 --> 00:14:02,730 And I'm not saying that-- what it indicates 227 00:14:02,730 --> 00:14:05,920 is that we know if you bind the receptor you'll reduce 228 00:14:05,920 --> 00:14:10,060 the effects of the [? rejections. ?] 229 00:14:10,060 --> 00:14:13,880 If the prefrontal cortex is functioning abnormally because 230 00:14:13,880 --> 00:14:16,385 of sprouting of these axons, also 231 00:14:16,385 --> 00:14:21,600 the basal forebrain, then binding to the receptors 232 00:14:21,600 --> 00:14:25,630 will move it more towards the normal. 233 00:14:25,630 --> 00:14:27,270 And that could be a reason. 234 00:14:27,270 --> 00:14:28,811 Just saying that it does [INAUDIBLE]. 235 00:14:36,360 --> 00:14:38,960 Let's talk about the other part of the basal ganglia, 236 00:14:38,960 --> 00:14:40,830 the larger part, the corpus striatum. 237 00:14:45,750 --> 00:14:48,265 Going back to these earlier pictures 238 00:14:48,265 --> 00:14:53,800 where I talked about the evolution, remember very early 239 00:14:53,800 --> 00:14:55,624 there was no dorsal striatum. 240 00:14:55,624 --> 00:14:58,395 It was more of an olfactory structure. 241 00:14:58,395 --> 00:15:00,720 But it was a link between the olfactory, [INAUDIBLE], 242 00:15:00,720 --> 00:15:02,580 and motor control. 243 00:15:02,580 --> 00:15:06,100 And that's what evolved into the ventral striatum. 244 00:15:06,100 --> 00:15:10,620 And we also know the outputs of that region 245 00:15:10,620 --> 00:15:14,320 go to hypothalamus and subthalamus. 246 00:15:14,320 --> 00:15:16,870 They influence the endocrine system and motivational states 247 00:15:16,870 --> 00:15:19,680 by these projections. 248 00:15:19,680 --> 00:15:23,629 They also have some connections in the midbrain, where 249 00:15:23,629 --> 00:15:26,366 they can influence the stacking patterns, especially 250 00:15:26,366 --> 00:15:26,866 locomotion. 251 00:15:31,030 --> 00:15:34,690 The ones to the midbrain are probably 252 00:15:34,690 --> 00:15:39,460 influencing all of these basic movement types. 253 00:15:39,460 --> 00:15:41,500 Although I'm not saying those were all there 254 00:15:41,500 --> 00:15:44,280 at the very beginning. 255 00:15:44,280 --> 00:15:48,455 And we also know that-- I'm postulating 256 00:15:48,455 --> 00:15:51,365 that very early this was a modifiable length. 257 00:15:51,365 --> 00:15:54,510 So it must've been modified because 258 00:15:54,510 --> 00:15:56,220 of feedback of some sort. 259 00:15:56,220 --> 00:16:00,570 And we know the feedback in modern animals 260 00:16:00,570 --> 00:16:04,040 is mostly dopamine systems, coming 261 00:16:04,040 --> 00:16:07,672 from, in most vertebrates, the hypothalamus, 262 00:16:07,672 --> 00:16:11,840 but in mammals and other amniotes, 263 00:16:11,840 --> 00:16:17,870 the birds and reptiles, also the skates and the rays-- sharks, 264 00:16:17,870 --> 00:16:23,178 skates, and rays comes from the ventral tegmental area. 265 00:16:28,920 --> 00:16:33,300 And we know that, especially if you look in fish, where 266 00:16:33,300 --> 00:16:40,842 the dopamine feedback comes from the hypothalamus, 267 00:16:40,842 --> 00:16:45,550 that a major input to the hypothalamus in those animals 268 00:16:45,550 --> 00:16:49,230 is from the taste [? cyst. ?] In mammals it's 269 00:16:49,230 --> 00:16:51,830 never been emphasized, but we know 270 00:16:51,830 --> 00:16:56,945 taste can be very rewarding and influences the tegmental area 271 00:16:56,945 --> 00:16:58,120 cells. 272 00:16:58,120 --> 00:17:00,420 The studies of rats have indicated yes, there 273 00:17:00,420 --> 00:17:04,275 are some projections, even in mammals, from that system. 274 00:17:04,275 --> 00:17:10,010 That's why I include it when I talk about the outputs 275 00:17:10,010 --> 00:17:12,759 to that region in this book. 276 00:17:12,759 --> 00:17:13,259 All right. 277 00:17:17,790 --> 00:17:21,934 Now we know that substantia nigra in the midbrain 278 00:17:21,934 --> 00:17:27,050 is a major recipient of outputs from the dorsal striatum. 279 00:17:31,580 --> 00:17:39,280 We also know that the nigra, the dorsal part of it, called 280 00:17:39,280 --> 00:17:43,475 the pars compacta because of the packing of the cells, 281 00:17:43,475 --> 00:17:48,720 is where the dopamine axons of the nigra are located. 282 00:17:48,720 --> 00:17:51,490 Because the dopamine cells in the midbrain 283 00:17:51,490 --> 00:17:53,540 are not just the ventral tegmental area. 284 00:17:53,540 --> 00:17:57,550 They're in the-- it's an essential projection 285 00:17:57,550 --> 00:18:01,960 to the normal function of the dorsal striatum. 286 00:18:01,960 --> 00:18:04,352 The ventral striatum gets its dopamine 287 00:18:04,352 --> 00:18:10,710 from the ventral tegmental area, not the dorsal striatal. 288 00:18:10,710 --> 00:18:13,390 The other part of the nigra's called the pars reticulata. 289 00:18:13,390 --> 00:18:16,420 It's more ventral. 290 00:18:16,420 --> 00:18:20,810 It has projections to systems influencing movement. 291 00:18:20,810 --> 00:18:25,130 They go to the [INAUDIBLE] and influence orienting. 292 00:18:25,130 --> 00:18:27,450 They also go to the midbrain locomotor area. 293 00:18:30,970 --> 00:18:33,500 They also project at thalamic nuclei 294 00:18:33,500 --> 00:18:37,590 that project to motor [INAUDIBLE] centric cortex. 295 00:18:43,610 --> 00:18:46,070 We pick those projections here. 296 00:18:46,070 --> 00:18:51,890 Now here, in this slide, I'm showing just the major dorsal 297 00:18:51,890 --> 00:18:55,600 striatal components, the caudate and the putamen. 298 00:18:55,600 --> 00:18:58,110 So what's in between the caudate and the putamen here? 299 00:18:58,110 --> 00:18:59,036 It filled a space. 300 00:19:02,740 --> 00:19:06,310 The internal capsule fibers coming from the cortex. 301 00:19:06,310 --> 00:19:11,970 So this picture is more for the larger mammals, that 302 00:19:11,970 --> 00:19:14,890 have an internal capsule that's separating 303 00:19:14,890 --> 00:19:17,052 the dorsal striatum into these two parts. 304 00:19:17,052 --> 00:19:22,280 If you're dealing with a rat or a mouse or a hamster, 305 00:19:22,280 --> 00:19:27,180 the internal capsule fibers sort of come in multiple bundles 306 00:19:27,180 --> 00:19:28,620 through the corpus striatum. 307 00:19:28,620 --> 00:19:30,940 So it doesn't make a whole lot of sense 308 00:19:30,940 --> 00:19:33,360 to talk about caudate putamen. 309 00:19:33,360 --> 00:19:36,080 So how come they just call it the caudate putamen 310 00:19:36,080 --> 00:19:39,780 or caudoputamen in these little animals? 311 00:19:39,780 --> 00:19:41,820 That's so you don't get too confused 312 00:19:41,820 --> 00:19:44,090 when you read this literature. 313 00:19:44,090 --> 00:19:46,840 But in cats and dogs and primates, 314 00:19:46,840 --> 00:19:49,206 in general you have a clear corpus striatum. 315 00:19:49,206 --> 00:19:52,060 So that's what I'm picturing here. 316 00:19:52,060 --> 00:19:55,720 And in the picture I'm showing the dopamine pathway 317 00:19:55,720 --> 00:20:00,550 in the pars compacta of the nigra, 318 00:20:00,550 --> 00:20:05,400 distributing throughout pretty densely to the whole dorsal 319 00:20:05,400 --> 00:20:06,780 striatum. 320 00:20:06,780 --> 00:20:10,965 And then I show the output from the caudate 321 00:20:10,965 --> 00:20:13,260 that goes to the nigra. 322 00:20:13,260 --> 00:20:17,848 It's a GABAergic projection. 323 00:20:17,848 --> 00:20:22,780 It acts by inhibiting the cells. 324 00:20:22,780 --> 00:20:25,875 Now, I also show the projection from the nigra 325 00:20:25,875 --> 00:20:28,640 here to the colliculus, nigra [INAUDIBLE] track 326 00:20:28,640 --> 00:20:31,010 that's also GABAergic. 327 00:20:31,010 --> 00:20:37,395 And I show it going forward into the medial structures 328 00:20:37,395 --> 00:20:42,090 of the thalamus, VM and-- the ventral medial 329 00:20:42,090 --> 00:20:46,660 and ventral anterior nuclei, which project pretty widely 330 00:20:46,660 --> 00:20:50,500 to motor and some of the sensory areas. 331 00:20:50,500 --> 00:20:53,110 So then the question is, if the nigra's 332 00:20:53,110 --> 00:20:56,315 signaling some kind of reward or punishment to the striatum, 333 00:20:56,315 --> 00:20:58,970 giving it some kind of feedback, well, 334 00:20:58,970 --> 00:21:02,510 where's that feedback originate? 335 00:21:02,510 --> 00:21:08,840 And there are some interactions between limbic system 336 00:21:08,840 --> 00:21:12,720 and somatic system in the nigra. 337 00:21:12,720 --> 00:21:14,840 There are connections from the amygdala. 338 00:21:14,840 --> 00:21:16,180 It's like I added here. 339 00:21:16,180 --> 00:21:17,780 This is the same picture, but I've 340 00:21:17,780 --> 00:21:22,210 added here the more caudally-located amygdala, 341 00:21:22,210 --> 00:21:25,780 and shown that it projects to the nigra. 342 00:21:25,780 --> 00:21:30,090 I've also shown here that lateral hypothalamus projects 343 00:21:30,090 --> 00:21:34,430 directly to the nigra also. 344 00:21:37,240 --> 00:21:39,200 So it does appear to be a place where 345 00:21:39,200 --> 00:21:44,570 the limbic system and somatic systems show some convergence. 346 00:21:44,570 --> 00:21:48,089 Which may be very important to how this whole structure 347 00:21:48,089 --> 00:21:48,588 functions. 348 00:21:52,860 --> 00:21:55,770 In the evolution of this structure 349 00:21:55,770 --> 00:21:58,660 you start out with the ventral area getting olfactory input. 350 00:21:58,660 --> 00:22:03,260 But then we know that non-olfactory inputs came in. 351 00:22:03,260 --> 00:22:07,810 And that led to expansion of the striatum, this area here. 352 00:22:07,810 --> 00:22:10,150 I showed how that's beginning to bulge, 353 00:22:10,150 --> 00:22:13,750 with these nice non-olfactory inputs. 354 00:22:13,750 --> 00:22:21,520 And we noted that led to some segregation 355 00:22:21,520 --> 00:22:27,920 of the olfactory part and the non-olfactory part. 356 00:22:27,920 --> 00:22:31,105 What was olfactory became the ventral striatum. 357 00:22:31,105 --> 00:22:35,150 And some of it still gets direct olfactory projections. 358 00:22:35,150 --> 00:22:39,800 Whereas sensory inputs come into the striatum. 359 00:22:39,800 --> 00:22:43,260 And I'm just showing you here for a rat 360 00:22:43,260 --> 00:22:46,390 or a hamster or a mouse. 361 00:22:46,390 --> 00:22:49,400 We know the intralaminar nuclei of the thalamus, 362 00:22:49,400 --> 00:22:52,831 that we call the paleothalamus, the older thalamus. 363 00:22:52,831 --> 00:22:55,360 They tend to get multi sensory inputs. 364 00:22:55,360 --> 00:22:59,430 A lot of them come from the superior colliculus, 365 00:22:59,430 --> 00:23:00,840 for example. 366 00:23:00,840 --> 00:23:01,830 They project here. 367 00:23:01,830 --> 00:23:06,650 And some of them come directly from this final thalamic tract. 368 00:23:06,650 --> 00:23:08,670 They project to these intralaminar nuclei. 369 00:23:08,670 --> 00:23:11,140 So I just lumped them together here. 370 00:23:11,140 --> 00:23:15,560 And we show that they have strong projections 371 00:23:15,560 --> 00:23:18,700 to the dorsal striatum. 372 00:23:18,700 --> 00:23:20,690 We also have some of these [? exons ?] 373 00:23:20,690 --> 00:23:22,440 extend right up into the hemisphere. 374 00:23:22,440 --> 00:23:25,522 So we'll see that here. 375 00:23:25,522 --> 00:23:29,140 And then of course I'm showing the cortical striatal 376 00:23:29,140 --> 00:23:30,420 connection there. 377 00:23:30,420 --> 00:23:34,790 And I'm showing the dopamine pathway as well. 378 00:23:34,790 --> 00:23:38,495 This shows you the same thing from the Brodal textbook, 379 00:23:38,495 --> 00:23:41,480 where he shows one part of the intralaminal nuclei. 380 00:23:41,480 --> 00:23:43,320 It's called the centromedian. 381 00:23:43,320 --> 00:23:46,170 It's because in primates that part, which 382 00:23:46,170 --> 00:23:48,430 is a caudal part of the intralaminal nuclei, 383 00:23:48,430 --> 00:23:50,555 has become particularly enlarged. 384 00:23:50,555 --> 00:23:57,170 So in humans it's very large also, and other large primates. 385 00:23:57,170 --> 00:23:59,980 But this is just to say this isn't just something that 386 00:23:59,980 --> 00:24:01,690 happened early in evolution. 387 00:24:01,690 --> 00:24:05,330 It actually enlarged in more recently evolution. 388 00:24:05,330 --> 00:24:12,860 As this one nucleus gets mixed non-olfactory inputs, 389 00:24:12,860 --> 00:24:17,300 projects strongly to the dorsal striatum. 390 00:24:17,300 --> 00:24:19,870 OK, and this shows you pictures of what that looks like. 391 00:24:19,870 --> 00:24:21,370 I have this one picture in the book. 392 00:24:21,370 --> 00:24:22,820 I have three here. 393 00:24:22,820 --> 00:24:26,160 This shows in a rat the parafiscicular nucleus, which 394 00:24:26,160 --> 00:24:28,835 was like the centromedian of primates. 395 00:24:28,835 --> 00:24:32,480 And you can see the widely branching axons 396 00:24:32,480 --> 00:24:34,140 terminating in the striatum. 397 00:24:34,140 --> 00:24:39,290 And here there's a branch going on into the cortex. 398 00:24:39,290 --> 00:24:42,390 It projects a little bit to other structures too. 399 00:24:42,390 --> 00:24:46,970 And here's one in the centralis lateralis. 400 00:24:46,970 --> 00:24:49,990 Little further forward in the intralaminal nuclei. 401 00:24:49,990 --> 00:24:57,916 It's also projecting to both the caudate or putamen-- here 402 00:24:57,916 --> 00:25:01,920 they're just calling it one structure, the caudoputamen-- 403 00:25:01,920 --> 00:25:04,580 and to the frontal motor cortex, in this case. 404 00:25:04,580 --> 00:25:07,420 And here's one that's not in the intralaminar. 405 00:25:07,420 --> 00:25:10,670 But it's in another ancient part of the thalamus. 406 00:25:10,670 --> 00:25:12,976 We call it the posterior group of nuclei. 407 00:25:12,976 --> 00:25:17,020 They're outside the areas of the thalamus that 408 00:25:17,020 --> 00:25:20,762 project to the primary sensory areas in the neocortex. 409 00:25:20,762 --> 00:25:22,440 They project the multimodal areas. 410 00:25:25,630 --> 00:25:30,740 They get multimodal input, and it shows them projecting again 411 00:25:30,740 --> 00:25:36,460 to the dorsal striatum and into the cortex. 412 00:25:36,460 --> 00:25:38,840 Now, I'm showing you pictures of axons 413 00:25:38,840 --> 00:25:40,670 that terminate in both places. 414 00:25:40,670 --> 00:25:42,450 Many of the neurons in those structures 415 00:25:42,450 --> 00:25:46,770 project to one or the other, either cortex or striatum. 416 00:25:46,770 --> 00:25:50,170 But because a number of them project this way, 417 00:25:50,170 --> 00:25:52,550 it emphasizes the point I want to make, 418 00:25:52,550 --> 00:25:55,630 that they're going to both structures. 419 00:25:55,630 --> 00:25:58,440 So in many cases they are separate neurons. 420 00:25:58,440 --> 00:26:04,760 OK, so then with the non-olfactory input, 421 00:26:04,760 --> 00:26:13,720 you had expansions of both the pallium and the striatum. 422 00:26:13,720 --> 00:26:14,980 Here's the pallium. 423 00:26:14,980 --> 00:26:16,370 Here's the striatum. 424 00:26:16,370 --> 00:26:19,080 Here I'm showing olfactory input going to both. 425 00:26:21,744 --> 00:26:26,320 The non-olfactory input into the pallium we know 426 00:26:26,320 --> 00:26:28,696 went through the thalamus, most of it. 427 00:26:35,020 --> 00:26:38,488 And then it also did the same for the dorsal striatum, 428 00:26:38,488 --> 00:26:39,897 but not the ventral striatum. 429 00:26:39,897 --> 00:26:41,730 The olfactory were [? displaced ?] separate. 430 00:26:45,410 --> 00:26:49,225 And then, of course, in more recent evolution of mammals 431 00:26:49,225 --> 00:26:54,235 we had this huge expansion when the pallium became 432 00:26:54,235 --> 00:26:57,310 an-- a part of it developed into neocortex, 433 00:26:57,310 --> 00:27:01,400 and that part is expanded so much. 434 00:27:01,400 --> 00:27:05,490 And those earlier outputs and inputs 435 00:27:05,490 --> 00:27:08,435 remain, even in modern mammals, when 436 00:27:08,435 --> 00:27:11,070 all that expands from the [INAUDIBLE]. 437 00:27:11,070 --> 00:27:14,630 But let's look now at-- this is a rodent. 438 00:27:14,630 --> 00:27:17,415 And this is the earlier picture. 439 00:27:17,415 --> 00:27:21,660 I put this one in the book. 440 00:27:21,660 --> 00:27:24,880 If you look at the hemisphere from the medial side, 441 00:27:24,880 --> 00:27:28,900 you can picture where the ventral striatum, 442 00:27:28,900 --> 00:27:31,950 dorsal striatum, and also the hippocampus are located. 443 00:27:31,950 --> 00:27:34,180 So here in the middle section you 444 00:27:34,180 --> 00:27:40,930 see the amygdala area, here. 445 00:27:40,930 --> 00:27:46,254 Further forward, the ventral striatum, down here. 446 00:27:46,254 --> 00:27:49,550 Dorsal striatum there. 447 00:27:49,550 --> 00:27:54,990 And very [INAUDIBLE], you see a structure 448 00:27:54,990 --> 00:27:56,750 related to the ventral striatum. 449 00:27:56,750 --> 00:27:59,070 It's really a caudal-- it's called 450 00:27:59,070 --> 00:28:03,410 the caudal amygdaloid area, sometimes hippocampal 451 00:28:03,410 --> 00:28:05,000 amygdaloid area. 452 00:28:05,000 --> 00:28:06,200 It's very [? part ?] caudal. 453 00:28:06,200 --> 00:28:09,740 It's right next to the hippocampus, which is in here. 454 00:28:09,740 --> 00:28:12,030 So that just gives you the picture 455 00:28:12,030 --> 00:28:14,730 of these subcortical structures of the hindbrain. 456 00:28:17,700 --> 00:28:20,330 So now we want to answer these kinds of questions. 457 00:28:20,330 --> 00:28:22,580 What are the two major outputs of the corpus striatum? 458 00:28:25,380 --> 00:28:29,200 Most of them are by way of the globus pallidus. 459 00:28:29,200 --> 00:28:34,050 You just deal with those, coming from the globus pallidus. 460 00:28:34,050 --> 00:28:37,800 One of them is much larger in mammals, 461 00:28:37,800 --> 00:28:44,090 which is why we sometimes talk about the extrapyramidal system 462 00:28:44,090 --> 00:28:46,220 projecting directly to the pyramidals. 463 00:28:48,900 --> 00:28:50,585 Because the extrapyramidal systems 464 00:28:50,585 --> 00:28:52,680 are the striatum, the cerebellum, 465 00:28:52,680 --> 00:28:55,640 and many other structures that aren't 466 00:28:55,640 --> 00:29:00,764 part of the corticospinal system. 467 00:29:00,764 --> 00:29:03,520 It's basically the pyramidal tract. 468 00:29:03,520 --> 00:29:04,950 So let's look at that. 469 00:29:08,990 --> 00:29:13,090 This one you can guess that the answer contrasts 470 00:29:13,090 --> 00:29:16,500 the major sorts of sensory input to the striatum in amphibians 471 00:29:16,500 --> 00:29:17,140 and in mammals. 472 00:29:20,070 --> 00:29:22,180 And just of the striatum. 473 00:29:22,180 --> 00:29:27,100 What is the big change that happened in mammals? 474 00:29:27,100 --> 00:29:30,240 In general, in the forebrain, what 475 00:29:30,240 --> 00:29:32,740 was the big change in mammals? 476 00:29:32,740 --> 00:29:35,410 Expansion of? 477 00:29:35,410 --> 00:29:36,900 The neocortex, right. 478 00:29:36,900 --> 00:29:39,690 The evolution of the neocortex that expanded. 479 00:29:39,690 --> 00:29:40,780 That happened in mammals. 480 00:29:40,780 --> 00:29:45,380 It didn't happen in the amphibians at all. 481 00:29:45,380 --> 00:29:47,510 Amphibians have this little dorsal cortex 482 00:29:47,510 --> 00:29:49,985 that's equivalent to a parahippocampal area. 483 00:29:49,985 --> 00:29:53,860 And they have a medial pallium. 484 00:29:53,860 --> 00:29:55,570 But none of it's like neocortex, really. 485 00:29:58,530 --> 00:30:02,970 Even though it does get some non-olfactory input. 486 00:30:02,970 --> 00:30:07,110 And then I'm asking a question that we've pretty much been 487 00:30:07,110 --> 00:30:09,566 answering, what's the limbic striatum? 488 00:30:09,566 --> 00:30:11,740 How does it differ from non-limbic striatum? 489 00:30:16,530 --> 00:30:18,690 And what are several structures that it includes? 490 00:30:18,690 --> 00:30:21,350 Well, I'm really asking what are the components 491 00:30:21,350 --> 00:30:23,810 of that ventral striatum? 492 00:30:23,810 --> 00:30:25,920 So we've shown it in some pictures, 493 00:30:25,920 --> 00:30:28,782 and we'll look at some more. 494 00:30:28,782 --> 00:30:31,215 They're just major parts of it which 495 00:30:31,215 --> 00:30:33,650 reoccur in the literature and the discussions, 496 00:30:33,650 --> 00:30:35,820 including discussions of human pathologies. 497 00:30:35,820 --> 00:30:39,245 So you should being to learn a few of those. 498 00:30:39,245 --> 00:30:39,745 All right. 499 00:30:44,400 --> 00:30:47,890 This is a simplified diagram of major outputs of the neocortex. 500 00:30:50,970 --> 00:30:53,920 And here I show the striatum as one 501 00:30:53,920 --> 00:30:57,540 of the major outputs of the neocortex. 502 00:30:57,540 --> 00:31:02,550 So if you compare now amphibians and mammals, 503 00:31:02,550 --> 00:31:04,840 we said amphibians don't even have a neocortex. 504 00:31:04,840 --> 00:31:09,876 So how is their dorsal striatum getting input coming 505 00:31:09,876 --> 00:31:12,320 from the thalamus, the older parts of the thalamus? 506 00:31:16,060 --> 00:31:20,580 It's the major part of the thalamus in those animals. 507 00:31:20,580 --> 00:31:24,170 Whereas in mammals the major input to the striatum, 508 00:31:24,170 --> 00:31:25,790 even though the striatum is still 509 00:31:25,790 --> 00:31:30,170 getting thalamic projections, as we've pointed out, 510 00:31:30,170 --> 00:31:35,200 now the neocortex is by far the larger structure. 511 00:31:35,200 --> 00:31:38,460 And it dominates the dorsal striatum, 512 00:31:38,460 --> 00:31:42,945 as it dominates a lot of the systems, because of its size. 513 00:31:42,945 --> 00:31:49,170 So this shows the cortical striatal connection. 514 00:31:49,170 --> 00:31:52,660 I show it connecting to the limbic hindbrain as well. 515 00:31:52,660 --> 00:31:58,190 And here I just included as part of the limbic hindbrain 516 00:31:58,190 --> 00:31:59,690 the ventral striatum. 517 00:31:59,690 --> 00:32:03,420 We'll separate that in a minute. 518 00:32:03,420 --> 00:32:06,790 But note that besides the striatum, 519 00:32:06,790 --> 00:32:13,510 the neocortex bypasses even the brain stem 520 00:32:13,510 --> 00:32:16,550 for its long connections. 521 00:32:16,550 --> 00:32:18,490 Because it has corticalspinal connections. 522 00:32:18,490 --> 00:32:21,100 So I have it here going to the brain stem and spinal cord 523 00:32:21,100 --> 00:32:22,280 directly. 524 00:32:22,280 --> 00:32:28,020 Whereas the striatum has a connection to the brain stem, 525 00:32:28,020 --> 00:32:32,740 relatively smaller, none to the spinal cord. 526 00:32:32,740 --> 00:32:36,270 But in mammals it does have a major connection 527 00:32:36,270 --> 00:32:40,750 back to the thalamus, which then goes to the motor and premotor 528 00:32:40,750 --> 00:32:43,340 areas of cortex. 529 00:32:43,340 --> 00:32:46,780 So that's how the striatum is influencing movement, 530 00:32:46,780 --> 00:32:48,350 primarily. 531 00:32:48,350 --> 00:32:50,265 Some by its connections to the midbrain, 532 00:32:50,265 --> 00:32:56,616 but then also much more through the thalamocortical connection, 533 00:32:56,616 --> 00:32:59,700 which affects the neocortical output. 534 00:33:02,800 --> 00:33:05,660 So it leaves out the ventral striatum. 535 00:33:05,660 --> 00:33:08,720 So those early stages of chordate evolution 536 00:33:08,720 --> 00:33:11,390 are just left out. 537 00:33:11,390 --> 00:33:15,630 So I made a more complex diagram that 538 00:33:15,630 --> 00:33:17,460 will drive you a little crazy. 539 00:33:17,460 --> 00:33:22,830 But what I've simply done is separate the somatic and limbic 540 00:33:22,830 --> 00:33:23,920 systems. 541 00:33:23,920 --> 00:33:26,060 If we just want to say, well what's 542 00:33:26,060 --> 00:33:27,990 most unique on the somatic side? 543 00:33:27,990 --> 00:33:29,580 What's most unique on the limbic side? 544 00:33:32,280 --> 00:33:35,980 What's the most unique thing about this somatic diagram 545 00:33:35,980 --> 00:33:36,480 here? 546 00:33:36,480 --> 00:33:38,950 It would be this long connection, directly 547 00:33:38,950 --> 00:33:40,700 to spinal cord. 548 00:33:40,700 --> 00:33:44,290 You don't see anything like that from the limbic system. 549 00:33:44,290 --> 00:33:46,480 The longest connections of the limbic system 550 00:33:46,480 --> 00:33:47,480 go into the midbrains. 551 00:33:47,480 --> 00:33:50,506 It's now-- they [? show ?] it in there much weaker. 552 00:33:50,506 --> 00:33:52,505 I didn't even show it here. 553 00:33:52,505 --> 00:33:56,260 It's a relatively weak projection. 554 00:33:56,260 --> 00:34:03,500 It just shows where the limbic midbrain is. 555 00:34:03,500 --> 00:34:06,840 Most of the connections are shorter for limbic system. 556 00:34:06,840 --> 00:34:09,500 So that's a major difference in the two sides. 557 00:34:09,500 --> 00:34:12,870 Another difference is in the [INAUDIBLE] length. 558 00:34:12,870 --> 00:34:21,050 Somatic system, the connections are to and from the thalamus. 559 00:34:21,050 --> 00:34:25,889 The limbic system, connections to and from the hypothalamus. 560 00:34:25,889 --> 00:34:30,560 And then in the striatum, dorsal striatum for somatic system, 561 00:34:30,560 --> 00:34:35,190 ventral striatum for the limbic system. 562 00:34:35,190 --> 00:34:37,540 The older picture of this was when 563 00:34:37,540 --> 00:34:41,469 we talked about the lateral and medial forebrain bundle. 564 00:34:41,469 --> 00:34:44,170 And you can see where the dorsal striatum 565 00:34:44,170 --> 00:34:47,699 is in those [? dissolved ?] pictures-- right there. 566 00:34:47,699 --> 00:34:51,120 And then these more ventral and ventromedial structures 567 00:34:51,120 --> 00:34:52,928 are ventral striatum. 568 00:34:52,928 --> 00:34:57,110 And they connect through the medial forebrain bundle. 569 00:34:59,690 --> 00:35:04,920 Whereas the dorsal striatum and neocortex, 570 00:35:04,920 --> 00:35:08,830 they connect to more caudal structures 571 00:35:08,830 --> 00:35:12,580 through the lateral forebrain bundle, which, remember, 572 00:35:12,580 --> 00:35:15,760 the most [INAUDIBLE] component of the lateral forebrain bundle 573 00:35:15,760 --> 00:35:20,670 is the internal capsule and the white matter 574 00:35:20,670 --> 00:35:23,725 at the hemisphere, shown on that side. 575 00:35:23,725 --> 00:35:25,880 And this is just is from another slide. 576 00:35:29,050 --> 00:35:34,230 So we can take these pictures, like this one, 577 00:35:34,230 --> 00:35:37,920 and make it much simpler to talk about the striatum. 578 00:35:37,920 --> 00:35:42,510 This is one based on a simplification 579 00:35:42,510 --> 00:35:44,690 of one of [INAUDIBLE] pictures. 580 00:35:44,690 --> 00:35:49,080 Shows cerebral cortex getting input from the thalamus 581 00:35:49,080 --> 00:35:51,155 and projecting to the striatum. 582 00:35:51,155 --> 00:35:53,450 They don't show the corticalspinal projections 583 00:35:53,450 --> 00:35:54,310 [INAUDIBLE]. 584 00:35:54,310 --> 00:35:58,830 I'm just showing the striatum here. 585 00:35:58,830 --> 00:36:03,610 And then we see its major outputs. 586 00:36:03,610 --> 00:36:07,790 And here, by including the pallidum, 587 00:36:07,790 --> 00:36:10,530 we show the major connection going to pallidum, 588 00:36:10,530 --> 00:36:13,860 but some connections directly to the substantia nigra. 589 00:36:13,860 --> 00:36:15,390 Those are the two main connections 590 00:36:15,390 --> 00:36:16,830 of the dorsal striata. 591 00:36:19,710 --> 00:36:23,350 So the pallidum, its biggest projection is to the thalamus. 592 00:36:26,200 --> 00:36:28,280 That information is going to neocortex. 593 00:36:30,960 --> 00:36:35,140 But it also has projections to the caudal midbrain. 594 00:36:35,140 --> 00:36:39,020 And here we're talking mainly about that midbrain locomotor 595 00:36:39,020 --> 00:36:39,520 region. 596 00:36:42,845 --> 00:36:46,790 The literature names it pedunculopontine nucleus, 597 00:36:46,790 --> 00:36:50,060 and not always called it by its full name, 598 00:36:50,060 --> 00:36:53,700 nucleus tegmenti pedunculopontinus 599 00:36:53,700 --> 00:36:58,290 [? paruscompacta. ?] Because it was one part, compact cell 600 00:36:58,290 --> 00:37:00,500 part of that region where the striatum had 601 00:37:00,500 --> 00:37:02,440 its main connection. 602 00:37:02,440 --> 00:37:06,330 But I use often the functional terms in the locomotor area, 603 00:37:06,330 --> 00:37:09,310 because it's the major part of that area which, when 604 00:37:09,310 --> 00:37:11,400 stimulated, leads to locomotion. 605 00:37:11,400 --> 00:37:15,230 Here I just call it the caudal midbrain. 606 00:37:15,230 --> 00:37:17,340 And similarly, here the other area 607 00:37:17,340 --> 00:37:20,320 that the striatum projects to, substantia nigra 608 00:37:20,320 --> 00:37:25,270 with its dopamine projections, and here, 609 00:37:25,270 --> 00:37:30,995 its connections to the other major midbrain 610 00:37:30,995 --> 00:37:33,940 structure of motor control, the superior 611 00:37:33,940 --> 00:37:41,240 colliculus for orienting the [INAUDIBLE] movements. 612 00:37:41,240 --> 00:37:43,948 So the nigra can modulate those kinds of movements 613 00:37:43,948 --> 00:37:44,948 through this connection. 614 00:37:49,740 --> 00:37:53,048 This term occurs in discussions of human neuroanatomy. 615 00:37:53,048 --> 00:37:55,020 So you should know what it means. 616 00:37:55,020 --> 00:37:56,992 It's one of these connections. 617 00:37:56,992 --> 00:37:58,210 It's this slide. 618 00:38:01,450 --> 00:38:04,580 That's the ansa. 619 00:38:04,580 --> 00:38:06,500 Let's find out why it's called that. 620 00:38:06,500 --> 00:38:10,832 It means the handle at the lenticular nucleus. 621 00:38:10,832 --> 00:38:14,670 We've not used the lenticular nucleus before in the class. 622 00:38:14,670 --> 00:38:17,170 We've not used ansa before. 623 00:38:17,170 --> 00:38:24,300 But it's the handle of the lentiform nucleus. 624 00:38:24,300 --> 00:38:26,890 Here is a picture of the human brain. 625 00:38:30,460 --> 00:38:36,940 And here's, of course, all cortex. 626 00:38:36,940 --> 00:38:40,440 This is the neocortex that's hidden 627 00:38:40,440 --> 00:38:42,840 in the depth of the Sylvian fissure. 628 00:38:42,840 --> 00:38:44,170 There's the Sylvian fissure. 629 00:38:50,170 --> 00:38:51,835 And there's the corpus striatum. 630 00:38:51,835 --> 00:38:53,260 There's the caudate up there. 631 00:38:53,260 --> 00:38:55,420 Here's the internal capsule. 632 00:38:55,420 --> 00:38:58,855 And on the lateral side we have the lentiform nucleus, 633 00:38:58,855 --> 00:39:02,240 which is the putamen plus the two 634 00:39:02,240 --> 00:39:05,250 segments of the [INAUDIBLE]. 635 00:39:05,250 --> 00:39:07,470 Thalamus on the other side there. 636 00:39:07,470 --> 00:39:10,540 This is where the internal capsules already going along 637 00:39:10,540 --> 00:39:13,665 the side of it. 638 00:39:13,665 --> 00:39:17,895 OK, the output of the globus pallidus here, 639 00:39:17,895 --> 00:39:23,700 that goes to the ventral anterior nucleus thalamus, 640 00:39:23,700 --> 00:39:29,760 follows this sort of a hook or a handle, 641 00:39:29,760 --> 00:39:31,010 just like the handle of a cup. 642 00:39:31,010 --> 00:39:34,753 And that's why it was called the ansa lenticularis. 643 00:39:34,753 --> 00:39:40,340 Because this group of nuclei, the corpus striata, 644 00:39:40,340 --> 00:39:44,430 dorsal striata structures is often 645 00:39:44,430 --> 00:39:46,278 referred to as the lentiform nucleus. 646 00:39:50,500 --> 00:39:53,030 And what they're doing is going around the edge 647 00:39:53,030 --> 00:39:58,100 of the [INAUDIBLE] here and then going back, forward, 648 00:39:58,100 --> 00:40:03,905 and in to the ventral anterior nucleus, primarily. 649 00:40:03,905 --> 00:40:05,855 You go to VL as well. 650 00:40:05,855 --> 00:40:08,640 The VL is dominated more by cerebellar input. 651 00:40:08,640 --> 00:40:13,055 The VA is dominated more by the [INAUDIBLE] injections. 652 00:40:17,050 --> 00:40:18,780 This shows you, if you want to see 653 00:40:18,780 --> 00:40:20,365 one of [INAUDIBLE] pictures. 654 00:40:20,365 --> 00:40:23,865 His are more complex than the ones like this that I've used. 655 00:40:23,865 --> 00:40:29,440 But he does show the projection from the motor areas of cortex 656 00:40:29,440 --> 00:40:34,410 to the caudoputamen, which then projects the globus pallidus. 657 00:40:34,410 --> 00:40:38,410 And here are the two projections, caudal midbrain 658 00:40:38,410 --> 00:40:39,590 and thalamus. 659 00:40:39,590 --> 00:40:46,230 And there's the curving pathway of the ansa lenticularis. 660 00:40:49,010 --> 00:40:53,080 So when you hear the term "satellites of the striatum," 661 00:40:53,080 --> 00:40:57,950 we always mean two structures that 662 00:40:57,950 --> 00:41:00,850 are essential for the way the corpus striatum functions 663 00:41:00,850 --> 00:41:05,835 in mammals-- the substantia nigra and one other structure 664 00:41:05,835 --> 00:41:07,716 that so far I've not named. 665 00:41:07,716 --> 00:41:09,090 But it's part of the subthalamus. 666 00:41:09,090 --> 00:41:11,000 It's the subthalamic nucleus. 667 00:41:14,140 --> 00:41:17,055 I want to show those structures in a network diagram. 668 00:41:21,050 --> 00:41:26,820 But first, look at-- these would make good homework problems. 669 00:41:26,820 --> 00:41:28,890 But I think you can figure them out. 670 00:41:28,890 --> 00:41:31,810 Contrast the pathway to motor cortex and the pathway 671 00:41:31,810 --> 00:41:35,490 to the superior colliculus from the dorsal striatum. 672 00:41:35,490 --> 00:41:38,690 Well, the ones of the motor cortex we've described here. 673 00:41:38,690 --> 00:41:45,160 So from dorsal striatum through that ansa lenticularis, 674 00:41:45,160 --> 00:41:50,100 so dorsal striatum to globus pallidus and then directly 675 00:41:50,100 --> 00:41:55,320 to the VA of the thalamus, which then projects to motor cortex. 676 00:41:55,320 --> 00:42:00,700 The one with the colliculus goes directly 677 00:42:00,700 --> 00:42:03,660 from the dorsal striatum to the nigra. 678 00:42:03,660 --> 00:42:08,354 And the nigra projects the superior colliculus. 679 00:42:08,354 --> 00:42:12,379 Those are the two different paths. 680 00:42:12,379 --> 00:42:14,920 And then you need to know what we mean by doubled inhibition. 681 00:42:20,110 --> 00:42:23,870 Here we're just looking at one of those satellites, the nigra. 682 00:42:23,870 --> 00:42:30,420 And notice excitatory input from cortex. 683 00:42:30,420 --> 00:42:33,120 The output is inhibitory. 684 00:42:33,120 --> 00:42:37,960 Inhibits the globus pallidus and inhibits the nigra. 685 00:42:37,960 --> 00:42:39,560 But then know that the projections 686 00:42:39,560 --> 00:42:44,020 of the globus pallidus and the nigra both are inhibitory. 687 00:42:44,020 --> 00:42:47,160 So you're inhibiting an inhibitory pathway. 688 00:42:47,160 --> 00:42:49,500 That's what we mean by double inhibition. 689 00:42:49,500 --> 00:42:53,150 Important for understanding the pathologyies when something 690 00:42:53,150 --> 00:42:57,620 goes wrong with these structures, 691 00:42:57,620 --> 00:43:02,380 as in Parkinson's disease, as in Huntington's chorea, 692 00:43:02,380 --> 00:43:04,180 and other basal ganglia disorders. 693 00:43:08,270 --> 00:43:15,150 Because you can get not just a reduced function. 694 00:43:15,150 --> 00:43:20,310 You can get enhanced, too much excitation. 695 00:43:20,310 --> 00:43:23,110 So then to control it you need some way 696 00:43:23,110 --> 00:43:27,170 to reduce-- either replace the misconnections 697 00:43:27,170 --> 00:43:31,190 or reduce the overexcitation. 698 00:43:31,190 --> 00:43:35,346 So this is where we'll come back next time. 699 00:43:35,346 --> 00:43:37,220 Just to point out a couple things about this, 700 00:43:37,220 --> 00:43:42,650 this is the worst diagram in the book, probably. 701 00:43:42,650 --> 00:43:46,216 But it's been important for people 702 00:43:46,216 --> 00:43:51,270 to see how knowing these connections 703 00:43:51,270 --> 00:43:52,750 explains some of the disorders. 704 00:43:56,420 --> 00:43:57,630 So we'll leave it here. 705 00:43:57,630 --> 00:44:00,750 But just note, if there's just a subthalamic nucleus-- 706 00:44:00,750 --> 00:44:01,960 here's the nigra down here. 707 00:44:01,960 --> 00:44:04,330 So these are the two main satellites 708 00:44:04,330 --> 00:44:06,850 of the corpus striatum, [? caught ?] 709 00:44:06,850 --> 00:44:08,900 it in putamen here. 710 00:44:08,900 --> 00:44:11,045 And note, I put excitatory connections 711 00:44:11,045 --> 00:44:14,680 in blue, inhibitory connections in red. 712 00:44:17,540 --> 00:44:24,920 I didn't color the dopamine pathway here, in the nigra. 713 00:44:24,920 --> 00:44:26,980 But note, the subthalamic nucleus 714 00:44:26,980 --> 00:44:28,490 is getting inhibitory connections 715 00:44:28,490 --> 00:44:29,800 from the globus pallidus. 716 00:44:29,800 --> 00:44:34,540 But it excites both segments of the globus pallidus 717 00:44:34,540 --> 00:44:36,744 and the nigra. 718 00:44:36,744 --> 00:44:39,140 OK? 719 00:44:39,140 --> 00:44:40,820 So it's unique in that way. 720 00:44:40,820 --> 00:44:43,640 And it's critical for the balance of this system. 721 00:44:46,600 --> 00:44:51,660 So anything that goes wrong with the subthalamic nucleus 722 00:44:51,660 --> 00:44:55,010 can cause major problems with movement. 723 00:44:55,010 --> 00:44:57,971 OK, so let's stop there today.