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 00:00:24,410 --> 00:00:26,250 PROFESSOR: Last time, we were talking 9 00:00:26,250 --> 00:00:30,240 about endogenous activity as one of the determinants of pattern 10 00:00:30,240 --> 00:00:32,119 movement. 11 00:00:32,119 --> 00:00:35,300 We know very little about that, except a little bit 12 00:00:35,300 --> 00:00:36,370 from invertebrates. 13 00:00:39,810 --> 00:00:41,950 Except we do know about circadian rhythms, 14 00:00:41,950 --> 00:00:49,000 which is a more general regulator of movement. 15 00:00:49,000 --> 00:00:53,440 And I've just summarized here the three major types 16 00:00:53,440 --> 00:01:02,260 of concepts that help us explain patterning in movement. 17 00:01:02,260 --> 00:01:06,720 But then there's a couple of things I've added here. 18 00:01:06,720 --> 00:01:12,300 Plasticity in these mechanisms-- we're 19 00:01:12,300 --> 00:01:14,185 learning about plasticity in synapses 20 00:01:14,185 --> 00:01:17,460 which will affect the first two here, but endogenous, 21 00:01:17,460 --> 00:01:21,270 CNS activity, especially when single cells generate it, 22 00:01:21,270 --> 00:01:24,655 they have these pacemaker proteins 23 00:01:24,655 --> 00:01:28,700 that are engaged in this constant cycle 24 00:01:28,700 --> 00:01:31,807 where they're changing membrane potential. 25 00:01:31,807 --> 00:01:33,890 There's just about nothing known about plasticity, 26 00:01:33,890 --> 00:01:36,490 and yet it would be critical if that 27 00:01:36,490 --> 00:01:40,125 were a mechanism for timing. 28 00:01:40,125 --> 00:01:46,100 And we know what a problem timing is in neuroscience. 29 00:01:46,100 --> 00:01:50,130 So I think that's a big deficiency in the field. 30 00:01:50,130 --> 00:01:52,370 And I also point out here, my other plus 31 00:01:52,370 --> 00:01:57,320 here is neuromodulators that can alter 32 00:01:57,320 --> 00:02:00,780 the overall state of the brain can alter 33 00:02:00,780 --> 00:02:03,280 how these patterns are produced. 34 00:02:03,280 --> 00:02:10,289 And that concept is being used in studies of invertebrates. 35 00:02:10,289 --> 00:02:13,577 Again, my example here is Eve Marder 36 00:02:13,577 --> 00:02:17,470 at Brandeis, who studied invertebrates for many years, 37 00:02:17,470 --> 00:02:22,210 and the patterning of how they control pattern movements. 38 00:02:22,210 --> 00:02:23,920 All right. 39 00:02:23,920 --> 00:02:26,640 The very last topic, which won't take us very long, 40 00:02:26,640 --> 00:02:31,430 is control of the overall state of the brain. 41 00:02:31,430 --> 00:02:34,300 I think the chapter is clear enough. 42 00:02:34,300 --> 00:02:39,930 You can read it, but I'll just review some major points. 43 00:02:39,930 --> 00:02:43,630 What controls it and how many states are possible. 44 00:02:43,630 --> 00:02:46,580 Nobody else tries to deal with how many states are possible, 45 00:02:46,580 --> 00:02:48,370 so I try it a little bit in this quote. 46 00:02:58,940 --> 00:03:04,010 So we want to know the anatomy of these changes 47 00:03:04,010 --> 00:03:05,930 in overall state of the brain. 48 00:03:05,930 --> 00:03:13,630 And we mean drastic changes in state, like going to sleep 49 00:03:13,630 --> 00:03:18,420 or becoming aroused from sleep or from drowsiness, becoming 50 00:03:18,420 --> 00:03:22,680 hyper-attentive, become dominated 51 00:03:22,680 --> 00:03:25,800 by some particular feeling or other. 52 00:03:25,800 --> 00:03:28,206 Even if it's something simple like a feeling of hunger, 53 00:03:28,206 --> 00:03:30,080 it can really change the state of your brain. 54 00:03:34,520 --> 00:03:38,430 And a lot of the states that we know, humans go through 55 00:03:38,430 --> 00:03:42,125 and animal probably do too, we don't know a lot about. 56 00:03:46,950 --> 00:03:49,020 We know some of the [? coralis, ?] 57 00:03:49,020 --> 00:03:51,660 because we can record electrical activity. 58 00:03:51,660 --> 00:03:54,230 That's what the electroencephalograph does. 59 00:03:54,230 --> 00:03:56,790 But it doesn't allow us to specify anywhere 60 00:03:56,790 --> 00:04:00,110 near the number of states that should be possible 61 00:04:00,110 --> 00:04:01,730 when we go through the anatomy. 62 00:04:01,730 --> 00:04:06,390 So there's two very different types 63 00:04:06,390 --> 00:04:15,440 of mechanisms that could control a change in brain state. 64 00:04:15,440 --> 00:04:19,290 One of them you don't hear much about. 65 00:04:19,290 --> 00:04:22,680 And that's, if you look at the top here, the second one, 66 00:04:22,680 --> 00:04:26,180 chemical secretions into the cerebral spinal fluid, 67 00:04:26,180 --> 00:04:30,660 which can affect a lot of the brain. 68 00:04:30,660 --> 00:04:32,990 The study I usually cite for this 69 00:04:32,990 --> 00:04:35,870 is a study that's often forgotten about. 70 00:04:35,870 --> 00:04:40,630 But if you have a sleeping rabbit and a wide awake rabbit 71 00:04:40,630 --> 00:04:43,330 and you have a cannula in the cerebrospinal fluid, 72 00:04:43,330 --> 00:04:46,080 if you take a little bit of the fluid out of the sleeping 73 00:04:46,080 --> 00:04:51,690 rabbit and inject that into the cerebral spinal fluid 74 00:04:51,690 --> 00:04:54,709 of the awake rabbit-- and of course you do the controls-- 75 00:04:54,709 --> 00:04:56,625 but anyway, the awake rabbit will go to sleep. 76 00:05:00,090 --> 00:05:04,340 Not studied very much, but I think the cerebral spinal fluid 77 00:05:04,340 --> 00:05:07,620 is a medium of conduction in the brain. 78 00:05:07,620 --> 00:05:11,450 It probably affects things other than the overall state, 79 00:05:11,450 --> 00:05:15,470 but at least we know that it is possible. 80 00:05:15,470 --> 00:05:19,450 What we do know more about is the widely 81 00:05:19,450 --> 00:05:21,910 projecting axonal systems. 82 00:05:21,910 --> 00:05:24,890 You know, if we deal with very primitive animals 83 00:05:24,890 --> 00:05:31,370 like amphioxus is just one example. 84 00:05:31,370 --> 00:05:34,160 Many invertebrates, in fact, if you 85 00:05:34,160 --> 00:05:38,190 look at their dendrites and their axons, 86 00:05:38,190 --> 00:05:41,310 it looks like they're all very widely spread, or at least many 87 00:05:41,310 --> 00:05:43,990 of them. 88 00:05:43,990 --> 00:05:47,450 Brains like ours become more compartmentalized, 89 00:05:47,450 --> 00:05:49,010 more specific, more specialized. 90 00:05:53,200 --> 00:05:58,620 But to achieve integration and changes in state, 91 00:05:58,620 --> 00:06:02,762 we have specialized systems with widely branching axons. 92 00:06:02,762 --> 00:06:03,550 All right. 93 00:06:06,970 --> 00:06:10,660 In this question, I ask you to describe four axonal systems. 94 00:06:10,660 --> 00:06:12,536 They're very widely projecting. 95 00:06:12,536 --> 00:06:14,410 What are those four that we usually think of? 96 00:06:20,140 --> 00:06:22,810 So cholinergic is the first. 97 00:06:22,810 --> 00:06:25,310 And we mentioned that when we were talking about brain stem. 98 00:06:25,310 --> 00:06:28,870 Remember, I showed those very widely branching axons 99 00:06:28,870 --> 00:06:29,840 of the hindbrain. 100 00:06:29,840 --> 00:06:31,415 Those are almost always cholinergic. 101 00:06:38,500 --> 00:06:44,370 What's a word that tells you-- monoaminergic. 102 00:06:44,370 --> 00:06:47,492 And what are the monoamines? 103 00:06:47,492 --> 00:06:49,270 AUDIENCE: [INAUDIBLE]. 104 00:06:49,270 --> 00:06:52,220 PROFESSOR: Those are the two catecholamines-- 105 00:06:52,220 --> 00:06:53,860 dopamine and norepinephrine. 106 00:06:53,860 --> 00:06:56,110 Those are both monoamines. 107 00:06:56,110 --> 00:06:59,200 But catecholamines are a subset of monoamines. 108 00:06:59,200 --> 00:07:01,970 And what's the other monoamine? 109 00:07:01,970 --> 00:07:05,280 Serotonin, 5-hydroxytryptamine. 110 00:07:05,280 --> 00:07:07,040 All right. 111 00:07:07,040 --> 00:07:09,970 And then, in more recent years, mainly 112 00:07:09,970 --> 00:07:14,500 due to discoveries at Harvard, like Cliff Saper, 113 00:07:14,500 --> 00:07:20,120 we know about other really widely branching systems. 114 00:07:20,120 --> 00:07:23,300 Now, when I was a student, we knew nothing about it. 115 00:07:23,300 --> 00:07:24,210 All right. 116 00:07:24,210 --> 00:07:26,440 So this is that example we had earlier 117 00:07:26,440 --> 00:07:31,870 of the widely branching catecholamine using neuron 118 00:07:31,870 --> 00:07:33,900 of the reticular formation, the hindbrain. 119 00:07:33,900 --> 00:07:36,890 You can see how widespread its distribution is. 120 00:07:36,890 --> 00:07:39,490 There are a number of them like this. 121 00:07:39,490 --> 00:07:41,720 Obviously, when they become active, 122 00:07:41,720 --> 00:07:44,400 they're affecting the state of the brain stem. 123 00:07:44,400 --> 00:07:47,620 And if you're affecting the thalamus here, 124 00:07:47,620 --> 00:07:50,180 these midline nuclei, their projecting tubes 125 00:07:50,180 --> 00:07:53,140 have axons that project to the specific nuclei that 126 00:07:53,140 --> 00:07:55,470 go to various cortical regions. 127 00:07:55,470 --> 00:07:58,270 So they're affecting the state of most 128 00:07:58,270 --> 00:08:02,200 of the central nervous system. 129 00:08:02,200 --> 00:08:05,710 This is a cartoon of the catecholamine systems. 130 00:08:05,710 --> 00:08:09,730 The neuron and the brain stem is like this one. 131 00:08:09,730 --> 00:08:12,933 But there's a group of neurons at the base of the brain-- 132 00:08:12,933 --> 00:08:14,820 nucleus basalis of Meynert. 133 00:08:14,820 --> 00:08:18,185 And there are neurons outside of nucleus basalis 134 00:08:18,185 --> 00:08:21,900 that project like this too. 135 00:08:21,900 --> 00:08:25,610 They don't include the acetylcholine 136 00:08:25,610 --> 00:08:27,557 containing axons in the striatum. 137 00:08:27,557 --> 00:08:28,515 Those are interneurons. 138 00:08:28,515 --> 00:08:30,330 They use acetylcholine. 139 00:08:30,330 --> 00:08:33,200 So all acetylcholine cells are not like this. 140 00:08:33,200 --> 00:08:36,185 But these are very widely projected. 141 00:08:39,059 --> 00:08:41,289 We usually hear about nucleus basalis 142 00:08:41,289 --> 00:08:43,200 in discussions of Alzheimer's disease 143 00:08:43,200 --> 00:08:45,230 because they tend to degenerate. 144 00:08:48,600 --> 00:08:55,840 And they project to the entire endbrain 145 00:08:55,840 --> 00:08:58,779 throughout the limbic system, throughout the neocortex. 146 00:08:58,779 --> 00:09:00,570 Here you see them going to the hippocampus. 147 00:09:03,230 --> 00:09:03,730 All right. 148 00:09:03,730 --> 00:09:06,900 So this is from a medical school book 149 00:09:06,900 --> 00:09:09,180 where you see them in the human brain. 150 00:09:09,180 --> 00:09:11,690 That's a little bit of optic chiasm 151 00:09:11,690 --> 00:09:14,660 that sort of fell off in histology, 152 00:09:14,660 --> 00:09:16,800 so it should be up here. 153 00:09:16,800 --> 00:09:19,290 But this is where nucleus basalis is. 154 00:09:19,290 --> 00:09:21,620 This is anterior [INAUDIBLE], so you're 155 00:09:21,620 --> 00:09:23,760 in front of the thalamus. 156 00:09:23,760 --> 00:09:25,740 You're in that basal forebrain region, 157 00:09:25,740 --> 00:09:27,340 which we'll be talking more about 158 00:09:27,340 --> 00:09:29,710 in the second half of class. 159 00:09:29,710 --> 00:09:32,830 This is all corpus striatum in here, 160 00:09:32,830 --> 00:09:35,500 where you find those acetylcholine interneurons. 161 00:09:35,500 --> 00:09:38,230 But the ones in the basal nucleus here, you can see, 162 00:09:38,230 --> 00:09:41,690 they just indicate their very widespread projections 163 00:09:41,690 --> 00:09:43,400 to the human hemisphere. 164 00:09:43,400 --> 00:09:47,900 And that's true of many other mammals as well. 165 00:09:47,900 --> 00:09:51,500 So here are the monoamine systems, serotonin, 166 00:09:51,500 --> 00:09:53,520 norepinephrine and dopamine, the catecholamines. 167 00:09:58,090 --> 00:10:00,920 The first two, serotonin and norepinephrine 168 00:10:00,920 --> 00:10:07,050 we know play major roles in the control of sleep and waking, 169 00:10:07,050 --> 00:10:11,260 and more generally in arousal states. 170 00:10:11,260 --> 00:10:17,410 The serotonin axons, which are very widely projecting, 171 00:10:17,410 --> 00:10:21,930 begin in these midline nuclei, the nuclei 172 00:10:21,930 --> 00:10:25,760 of the raphe in the brain stem-- midbrain and hindbrain. 173 00:10:28,940 --> 00:10:32,145 You already find those kinds of axons in amphioxus, 174 00:10:32,145 --> 00:10:37,720 so they're throughout all of the chordate kingdom. 175 00:10:37,720 --> 00:10:44,129 And we know they're important in humans at least 176 00:10:44,129 --> 00:10:45,045 in mood stabilization. 177 00:10:49,980 --> 00:10:52,245 We give re-uptake inhibitors like Prozac 178 00:10:52,245 --> 00:10:56,830 that affect human mood control and prevent 179 00:10:56,830 --> 00:10:58,220 the wide swings in mood. 180 00:11:01,890 --> 00:11:04,420 They also occasionally cause people to commit suicide. 181 00:11:04,420 --> 00:11:06,670 But if I'm giving an announcement on TV, 182 00:11:06,670 --> 00:11:07,780 I've got to say that. 183 00:11:07,780 --> 00:11:10,325 This can cause death, this can cause this, 184 00:11:10,325 --> 00:11:12,360 that-- I would never take any of those 185 00:11:12,360 --> 00:11:15,530 when I hear those commercials. 186 00:11:15,530 --> 00:11:18,080 And then the catecholamines, like norepinephrine, 187 00:11:18,080 --> 00:11:22,215 we know it's also very important in arousal states. 188 00:11:22,215 --> 00:11:24,595 And we know it does play specific roles 189 00:11:24,595 --> 00:11:27,405 in switching from one state, sleep, to another. 190 00:11:30,300 --> 00:11:32,640 And dopamine has more specific effects. 191 00:11:32,640 --> 00:11:37,010 It has somewhat more limited distribution-- 192 00:11:37,010 --> 00:11:39,580 not as limited as we used to think. 193 00:11:39,580 --> 00:11:44,778 But we know it's very important in reward and reinforcement 194 00:11:44,778 --> 00:11:47,110 types of learning. 195 00:11:47,110 --> 00:11:52,100 So this is a typical medical school illustration 196 00:11:52,100 --> 00:11:53,740 of these widely projecting axons. 197 00:11:53,740 --> 00:11:57,590 It basically shows you in sort of a cartoon 198 00:11:57,590 --> 00:12:00,530 form, where the cells are. 199 00:12:00,530 --> 00:12:04,930 These are right on the monoamine in the brain stem. 200 00:12:04,930 --> 00:12:06,840 So this is that huge pons. 201 00:12:06,840 --> 00:12:12,690 You can see, these are mostly in the hindbrain. 202 00:12:12,690 --> 00:12:14,636 And it shows them-- I think this is 203 00:12:14,636 --> 00:12:19,700 a later one from Lennart Heimer's books. 204 00:12:19,700 --> 00:12:22,320 You can see, it projects down to the spinal cord, 205 00:12:22,320 --> 00:12:25,200 projects to the cerebellum, projects to the thalamus, 206 00:12:25,200 --> 00:12:29,415 projects everywhere-- very widely projecting, 207 00:12:29,415 --> 00:12:33,150 and that's really all you can get out of these. 208 00:12:33,150 --> 00:12:35,570 But there is a little more specific knowledge 209 00:12:35,570 --> 00:12:39,160 about the serotonin axons if you look at the raphe nuclei 210 00:12:39,160 --> 00:12:42,072 here in the caudal midbrain. 211 00:12:42,072 --> 00:12:45,425 You'll see that there's a dorsal and a more ventral raphe 212 00:12:45,425 --> 00:12:46,250 nucleus. 213 00:12:46,250 --> 00:12:49,830 And they give rise to somewhat different axons. 214 00:12:49,830 --> 00:12:51,760 They look different. 215 00:12:51,760 --> 00:12:57,560 This is called a thin varicose axon system. 216 00:12:57,560 --> 00:13:03,920 And here's a very different kind of axon system. 217 00:13:03,920 --> 00:13:06,050 They called it basket axons. 218 00:13:06,050 --> 00:13:11,100 They've got thicker branches and different, larger endings. 219 00:13:11,100 --> 00:13:15,910 And if you look at a place like hippocampus or striatum, 220 00:13:15,910 --> 00:13:18,571 you see those two structures get only one of those two types. 221 00:13:21,160 --> 00:13:25,320 See, the basket axons are going into the dentate gyrus. 222 00:13:25,320 --> 00:13:27,430 The striatum is getting the thin varicose axons. 223 00:13:27,430 --> 00:13:30,500 But they're both going into the neocortex. 224 00:13:30,500 --> 00:13:34,720 And we don't know nearly enough about separate functions 225 00:13:34,720 --> 00:13:42,900 of those two types of axon for the serotonin system. 226 00:13:42,900 --> 00:13:45,980 And now here's a picture of the norepinephrine. 227 00:13:45,980 --> 00:13:50,540 These are amazing cells that you find in this area here called 228 00:13:50,540 --> 00:13:54,110 the locus coeruleus, named because of the blue pigment 229 00:13:54,110 --> 00:13:55,740 there. 230 00:13:55,740 --> 00:13:59,390 In rats, there's literally just a few hundred cells, 231 00:13:59,390 --> 00:14:02,800 and it projects everywhere. 232 00:14:02,800 --> 00:14:06,460 And they're very thin axons. 233 00:14:06,460 --> 00:14:08,037 And the cells aren't all that big, 234 00:14:08,037 --> 00:14:12,440 and yet they project more widely than any type 235 00:14:12,440 --> 00:14:15,500 of cell in the brain. 236 00:14:15,500 --> 00:14:21,010 There is a group in the lateral tegmentum of the hindbrain that 237 00:14:21,010 --> 00:14:23,810 also projects, but less widely. 238 00:14:23,810 --> 00:14:26,367 It's these locus coeruleus cells that 239 00:14:26,367 --> 00:14:27,700 project to the entire forebrain. 240 00:14:30,430 --> 00:14:32,240 And it's interesting, because if you 241 00:14:32,240 --> 00:14:40,050 give a toxin for the norepinephrine axons, 242 00:14:40,050 --> 00:14:41,830 just by giving this early in life, 243 00:14:41,830 --> 00:14:47,120 you can destroy all these axons going into the endbrain. 244 00:14:47,120 --> 00:14:52,020 And when you do that, you don't kill the cells. 245 00:14:52,020 --> 00:14:56,090 Instead, they compensate by increasing their projection 246 00:14:56,090 --> 00:14:58,310 at the brain stem. 247 00:14:58,310 --> 00:15:02,730 So the whole brain stem gets super-dense norepinephrine 248 00:15:02,730 --> 00:15:03,690 innervation. 249 00:15:03,690 --> 00:15:06,391 It's a kind of pruning effect of the sort 250 00:15:06,391 --> 00:15:08,470 that we've seen in the [INAUDIBLE] system. 251 00:15:08,470 --> 00:15:09,900 All right. 252 00:15:09,900 --> 00:15:19,340 And this shows the noradrenaline system in the rat. 253 00:15:19,340 --> 00:15:24,100 And the one I put in the book is this one. 254 00:15:24,100 --> 00:15:29,282 It's exactly that figure, except I took out a lot, 255 00:15:29,282 --> 00:15:35,370 for the simple reason that some of these are just mistakes. 256 00:15:35,370 --> 00:15:38,910 They're drawn anatomically incorrect. 257 00:15:38,910 --> 00:15:41,335 I have the advantage of being a neuroanatomist, 258 00:15:41,335 --> 00:15:44,430 and I notice these things when I read 259 00:15:44,430 --> 00:15:48,200 these summary figures that people mess up a bit. 260 00:15:48,200 --> 00:15:52,980 But what I am showing here is that even in the brain stem, 261 00:15:52,980 --> 00:15:55,705 even though the norepinephrine may be a little less 262 00:15:55,705 --> 00:16:01,160 in the spinal cord, cerebellum, and midbrain, it's still there. 263 00:16:01,160 --> 00:16:07,100 It's densest in the endbrain. 264 00:16:07,100 --> 00:16:07,860 All right. 265 00:16:07,860 --> 00:16:10,880 And then here's the dopamine system. 266 00:16:10,880 --> 00:16:16,620 Here's an earlier figure, and here's a later figure. 267 00:16:16,620 --> 00:16:20,230 This earlier figure is what you see in most medical books. 268 00:16:20,230 --> 00:16:23,520 It shows that in the neocortex, it's prefrontal. 269 00:16:26,720 --> 00:16:32,086 And then it also goes into limbic structures. 270 00:16:32,086 --> 00:16:41,310 So you see it going into hippocampus septum, amygdala, 271 00:16:41,310 --> 00:16:44,850 and they show it originating in these two structures we've 272 00:16:44,850 --> 00:16:47,000 talked about in the midbrain. 273 00:16:47,000 --> 00:16:51,540 We've mainly so far talked about the ventral tegmental area. 274 00:16:51,540 --> 00:16:55,270 And we defined the limbic midbrain areas. 275 00:16:55,270 --> 00:16:57,530 It's the area that's closely connected 276 00:16:57,530 --> 00:16:59,760 to the forebrain limbic system structures. 277 00:17:02,700 --> 00:17:04,859 But then more recent as these techniques 278 00:17:04,859 --> 00:17:07,119 have become more sensitive, they discovered, 279 00:17:07,119 --> 00:17:09,070 well, there is a lighter projection 280 00:17:09,070 --> 00:17:13,750 that goes all the way back, including into the hippocampus, 281 00:17:13,750 --> 00:17:16,725 including into the visual areas of the cortex, that 282 00:17:16,725 --> 00:17:18,849 does use dopamine. 283 00:17:18,849 --> 00:17:22,990 And there's even some going into the midbrain. 284 00:17:22,990 --> 00:17:24,839 There's been a little debate about that. 285 00:17:24,839 --> 00:17:27,420 I show it coming here from-- this 286 00:17:27,420 --> 00:17:32,810 is my figure, which was a modification of a summary 287 00:17:32,810 --> 00:17:36,170 figure by people that had studied the system earlier 288 00:17:36,170 --> 00:17:40,060 and had this kind of pattern. 289 00:17:40,060 --> 00:17:44,930 It could be these other groups here give rise to the midbrain, 290 00:17:44,930 --> 00:17:47,830 dopamine, and we still don't know a lot 291 00:17:47,830 --> 00:17:51,895 about the functions of that in all these structures. 292 00:17:54,550 --> 00:18:00,550 Notice that there are dopamine cells in the olfactory bulb 293 00:18:00,550 --> 00:18:02,080 as well. 294 00:18:02,080 --> 00:18:04,970 All right. 295 00:18:04,970 --> 00:18:07,360 Well, it turns out, those four systems 296 00:18:07,360 --> 00:18:09,870 are not the only systems, as I mentioned. 297 00:18:09,870 --> 00:18:12,850 We already knew that in the thalamus, the older 298 00:18:12,850 --> 00:18:15,990 parts of the thalamus, there are cell groups 299 00:18:15,990 --> 00:18:17,750 with very widespread projection. 300 00:18:17,750 --> 00:18:23,150 There's one located right on the midline that was studied here 301 00:18:23,150 --> 00:18:27,290 at MIT in Nauta's lab by Miles Herkenham, who's 302 00:18:27,290 --> 00:18:29,105 worked for many years at NIH. 303 00:18:32,390 --> 00:18:34,905 He found that this little cell group projects 304 00:18:34,905 --> 00:18:39,750 to the entire neocortex, but just way up in layer one. 305 00:18:39,750 --> 00:18:43,430 So it's only getting to the dendrites of the neurons 306 00:18:43,430 --> 00:18:44,688 all over the neocortex. 307 00:18:48,110 --> 00:18:49,830 That's this one. 308 00:18:52,626 --> 00:18:57,210 But since then, and I mentioned Cliff Saper at Harvard, 309 00:18:57,210 --> 00:18:59,640 discovered a number of cell groups 310 00:18:59,640 --> 00:19:01,560 that also project very widely. 311 00:19:01,560 --> 00:19:06,610 Not quite as widely, perhaps, as the norepinephrine, serotonin. 312 00:19:06,610 --> 00:19:10,780 One of them uses melanin concentrating hormone. 313 00:19:10,780 --> 00:19:15,000 Another uses the peptides hypocretin and orexin. 314 00:19:15,000 --> 00:19:18,350 They were well known because defects 315 00:19:18,350 --> 00:19:23,990 in the gene for those substances that 316 00:19:23,990 --> 00:19:26,940 are used as neurotransmitters in the system 317 00:19:26,940 --> 00:19:32,030 leads to forms of narcolepsy. 318 00:19:32,030 --> 00:19:41,640 And some of those connections are still not fully understood. 319 00:19:41,640 --> 00:19:45,113 There's another system that uses corticotropin releasing 320 00:19:45,113 --> 00:19:53,650 hormone, a hormone that's found, for example, 321 00:19:53,650 --> 00:19:54,780 a lot in the amygdala. 322 00:19:57,580 --> 00:20:01,560 And it was initially known just from anorexia states, 323 00:20:01,560 --> 00:20:06,750 but now we know it is more widespread. 324 00:20:06,750 --> 00:20:10,590 This is one picture from those studies. 325 00:20:10,590 --> 00:20:14,890 In this particular picture, they show 326 00:20:14,890 --> 00:20:19,730 on the right in blue the distribution of norepinephrine. 327 00:20:19,730 --> 00:20:21,870 Remember, I used blue for norepinephrine 328 00:20:21,870 --> 00:20:23,860 in that rat picture before. 329 00:20:23,860 --> 00:20:28,480 And here you see it distributed all over the neocortex, all 330 00:20:28,480 --> 00:20:32,585 over the limbic cortex down here, and in the hippocampus, 331 00:20:32,585 --> 00:20:36,910 throughout the thalamus and hypothalamus. 332 00:20:36,910 --> 00:20:42,100 But in red, on the left, they show these orexin hypocretin 333 00:20:42,100 --> 00:20:43,990 cells. 334 00:20:43,990 --> 00:20:47,345 And their axons are distributed very widely. 335 00:20:47,345 --> 00:20:51,900 They're most concentrated in the hypothalamus and parts 336 00:20:51,900 --> 00:20:53,340 of the amygdala. 337 00:20:53,340 --> 00:20:55,410 But then, in a more scattered way, 338 00:20:55,410 --> 00:21:00,696 you find them throughout most of the rest of the hemisphere. 339 00:21:00,696 --> 00:21:05,100 So it's another widely branching system. 340 00:21:05,100 --> 00:21:07,475 So that leads me, then, to that final topic, 341 00:21:07,475 --> 00:21:09,480 well, how many brain states are possible? 342 00:21:09,480 --> 00:21:12,260 So what I did for this is just make 343 00:21:12,260 --> 00:21:14,960 some simplifying assumptions. 344 00:21:14,960 --> 00:21:19,825 I say, let's just take four of these systems of the brain 345 00:21:19,825 --> 00:21:24,060 stem, and let's say that they just 346 00:21:24,060 --> 00:21:26,415 have three possible states-- no activity, 347 00:21:26,415 --> 00:21:28,120 low activity, high activity. 348 00:21:30,960 --> 00:21:34,770 And then we add to that four of these diencephalic 349 00:21:34,770 --> 00:21:38,880 state-changing systems and make the same assumption, 350 00:21:38,880 --> 00:21:40,520 they have three possible states. 351 00:21:40,520 --> 00:21:43,620 So that gives you eight systems. 352 00:21:43,620 --> 00:21:45,970 Now, if we assume they can operate independently, 353 00:21:45,970 --> 00:21:51,240 and there are actually some interconnections between them. 354 00:21:51,240 --> 00:21:55,160 But if we assume they can operate largely independently, 355 00:21:55,160 --> 00:21:57,760 then the number of possible states 356 00:21:57,760 --> 00:22:02,241 would be three to the eighth, 6,561 states. 357 00:22:02,241 --> 00:22:03,740 And if you just assume that it could 358 00:22:03,740 --> 00:22:08,850 have four possible states, it goes up to 65,536 states. 359 00:22:08,850 --> 00:22:13,410 So that's what I mean when we say that-- and these are very 360 00:22:13,410 --> 00:22:15,585 easy assumptions to make, because studies 361 00:22:15,585 --> 00:22:17,287 of the activities of interneurons 362 00:22:17,287 --> 00:22:21,050 indicate that they might have many more possible states 363 00:22:21,050 --> 00:22:24,670 than the few I'm assuming here. 364 00:22:29,130 --> 00:22:32,680 Just remember these states are largely 365 00:22:32,680 --> 00:22:36,970 independent of sensory motor cognitive activity. 366 00:22:36,970 --> 00:22:41,220 They certainly interact with the emotional activities, 367 00:22:41,220 --> 00:22:46,170 motivational states, but they appear 368 00:22:46,170 --> 00:22:49,811 to operate pretty independent of those as well. 369 00:22:49,811 --> 00:22:52,940 All right. 370 00:22:52,940 --> 00:22:54,770 This is just a little about the evolution 371 00:22:54,770 --> 00:23:03,690 where amphioxus is missing norepinephrine. 372 00:23:03,690 --> 00:23:07,720 It has dopamine and serotonin. 373 00:23:07,720 --> 00:23:13,210 Hagfish and lamprey, still very primitive vertebrates, 374 00:23:13,210 --> 00:23:14,480 have all of those systems. 375 00:23:14,480 --> 00:23:18,725 They may not have all of the others I mentioned. 376 00:23:18,725 --> 00:23:19,671 All right. 377 00:23:22,510 --> 00:23:28,275 We've already said what we need to say about those things. 378 00:23:28,275 --> 00:23:32,820 So I'll go on to what you guys are most interested in here. 379 00:23:36,556 --> 00:23:37,960 This is what I did. 380 00:23:37,960 --> 00:23:42,920 Now, first of all, you had that homework three, 381 00:23:42,920 --> 00:23:44,670 where I gave you the worksheets and I 382 00:23:44,670 --> 00:23:46,580 told you to do this stuff. 383 00:23:46,580 --> 00:23:49,320 Any of that's fair game for the exam. 384 00:23:49,320 --> 00:23:53,570 If you did it, you're already prepared there. 385 00:23:53,570 --> 00:23:57,610 And then I selected questions on the book chapters. 386 00:23:57,610 --> 00:24:02,022 So for chapters one and two, I only took seven. 387 00:24:02,022 --> 00:24:04,940 Chapters three and four, just again, 388 00:24:04,940 --> 00:24:06,759 a small group of questions. 389 00:24:10,982 --> 00:24:12,690 In fact, that goes beyond three and four. 390 00:24:12,690 --> 00:24:14,875 That's five to seven. 391 00:24:14,875 --> 00:24:20,040 So three and four, again, there's only five questions. 392 00:24:20,040 --> 00:24:27,163 So I'm reducing the number of questions a lot. 393 00:24:27,163 --> 00:24:30,270 And I've divided it according to the book chapters. 394 00:24:30,270 --> 00:24:32,730 These aren't classes, because they don't always 395 00:24:32,730 --> 00:24:34,670 match completely. 396 00:24:34,670 --> 00:24:38,380 So I used book chapters here to get these questions. 397 00:24:42,640 --> 00:24:45,456 So it still comes out to quite a few questions. 398 00:24:45,456 --> 00:24:46,940 There are 74 questions. 399 00:24:46,940 --> 00:24:48,420 And then I listed some names. 400 00:24:48,420 --> 00:24:50,470 Are there any names here you cannot remember? 401 00:24:54,930 --> 00:24:57,072 Remember Fritsch and Hitzig were? 402 00:24:57,072 --> 00:24:58,530 That might be a more difficult one. 403 00:24:58,530 --> 00:25:00,196 Those are the guys that mapped the motor 404 00:25:00,196 --> 00:25:01,500 cortex for the first time. 405 00:25:01,500 --> 00:25:05,480 They did it in dogs and humans during the Franco-Prussian War. 406 00:25:08,070 --> 00:25:11,565 They found this one area with the lowest thresholds, 407 00:25:11,565 --> 00:25:14,951 the smallest currents they could still elicit movement. 408 00:25:14,951 --> 00:25:17,306 And they defined that as the motor cortex. 409 00:25:20,180 --> 00:25:23,320 I left Betz out, the guy that discovered the giant cells 410 00:25:23,320 --> 00:25:23,820 there. 411 00:25:23,820 --> 00:25:26,710 You should certainly remember who Ramon y Cajal was 412 00:25:26,710 --> 00:25:28,120 and that he used the Golgi stain. 413 00:25:30,690 --> 00:25:32,550 He was a very comprehensive neuroanatomist. 414 00:25:32,550 --> 00:25:35,555 He studied the entire central nervous system 415 00:25:35,555 --> 00:25:38,770 and some of the peripheral nervous system as well. 416 00:25:38,770 --> 00:25:40,716 His brother, Pedro Ramon, was more 417 00:25:40,716 --> 00:25:42,625 of a comparative anatomist. 418 00:25:42,625 --> 00:25:45,710 Whereas Ramon y Cajal studied mammals. 419 00:25:49,160 --> 00:25:52,180 Sherrington-- what did Sherrington do? 420 00:25:52,180 --> 00:25:53,810 He was a physiologist. 421 00:25:53,810 --> 00:25:56,500 He worked out the properties of synapses 422 00:25:56,500 --> 00:25:59,880 before we could see synapses with the electron microscope. 423 00:25:59,880 --> 00:26:04,590 He knew about inhibitory and excitatory synapses. 424 00:26:04,590 --> 00:26:05,830 He knew about thresholds. 425 00:26:05,830 --> 00:26:09,510 He understood how neurons work. 426 00:26:09,510 --> 00:26:11,530 In fact, his article on the spinal cord, 427 00:26:11,530 --> 00:26:15,750 he studied mainly spinal animals, spinal [? calves ?] 428 00:26:15,750 --> 00:26:21,110 largely-- that is, an animal with a spinal cord transected, 429 00:26:21,110 --> 00:26:27,630 and he artificially respirated them for a lot of his studies. 430 00:26:27,630 --> 00:26:31,280 He wrote the article in Encyclopedia Britannica 431 00:26:31,280 --> 00:26:34,280 on the spinal cord, and I believe 432 00:26:34,280 --> 00:26:36,389 a modified version of it is still 433 00:26:36,389 --> 00:26:38,180 used in the Encyclopedia Britannica, that's 434 00:26:38,180 --> 00:26:38,960 how good it was. 435 00:26:38,960 --> 00:26:42,830 Even though this guy worked-- he was 436 00:26:42,830 --> 00:26:49,450 working at the previous turn of the century, early 1900s. 437 00:26:49,450 --> 00:26:55,170 And Otto Loewi, discoverer of chemical transformation. 438 00:26:55,170 --> 00:26:57,450 He studied the heart, remember? 439 00:26:57,450 --> 00:27:00,550 His famous experiments on the accelerator and decelerator 440 00:27:00,550 --> 00:27:02,770 nerves of the heart. 441 00:27:02,770 --> 00:27:09,320 Hans Spemann, he's credited with the discovery of induction 442 00:27:09,320 --> 00:27:14,410 of the nervous system by a specific tissue that 443 00:27:14,410 --> 00:27:17,320 turns out to be the notochord. 444 00:27:17,320 --> 00:27:20,147 And now we even know the molecule. 445 00:27:20,147 --> 00:27:21,230 You remember the molecule? 446 00:27:25,350 --> 00:27:28,240 Sonic the Hedgehog. 447 00:27:28,240 --> 00:27:29,700 I don't think I put that here. 448 00:27:33,304 --> 00:27:36,250 I don't think I did. 449 00:27:36,250 --> 00:27:40,200 But Rexed may be the most difficult one. 450 00:27:40,200 --> 00:27:43,180 That was the guy who gave the layers to the spinal cord. 451 00:27:43,180 --> 00:27:47,842 He changed the way we talk about the anatomy of the spinal cord, 452 00:27:47,842 --> 00:27:50,960 the way we use his numbers all the time. 453 00:27:50,960 --> 00:27:53,520 Ross Harrison, first used tissue culture. 454 00:27:53,520 --> 00:27:59,370 He was one of the first guys to see living growth cones. 455 00:27:59,370 --> 00:28:01,225 We First saw those in tissue culture. 456 00:28:06,180 --> 00:28:09,840 Karl Lashley is actually better known 457 00:28:09,840 --> 00:28:13,370 as the pioneer in physiological psychology, 458 00:28:13,370 --> 00:28:16,140 or brain and behavior studies, that 459 00:28:16,140 --> 00:28:18,480 are experimental in nature. 460 00:28:18,480 --> 00:28:20,510 There were of course many clinical neurologists 461 00:28:20,510 --> 00:28:22,400 before Lashley. 462 00:28:22,400 --> 00:28:27,450 But he took the methods of experimental psychology, 463 00:28:27,450 --> 00:28:29,480 controlled experiments, and applied it 464 00:28:29,480 --> 00:28:32,310 to studies of brain and behavior. 465 00:28:32,310 --> 00:28:38,290 And he was the one who wrote about-- I mention him twice, 466 00:28:38,290 --> 00:28:40,736 actually three times in the class. 467 00:28:40,736 --> 00:28:43,300 If you want to find it, most of you 468 00:28:43,300 --> 00:28:48,232 can probably search that text, right, and find his name. 469 00:28:48,232 --> 00:28:49,690 But the last time he was mentioned, 470 00:28:49,690 --> 00:28:51,990 it was because he wrote that famous paper, 471 00:28:51,990 --> 00:28:53,930 "The Problem of Serial Order in Behavior," 472 00:28:53,930 --> 00:28:57,990 proving that rapid learned movements of humans 473 00:28:57,990 --> 00:29:01,860 had to be centrally programmed. 474 00:29:01,860 --> 00:29:04,710 So when we over-learn something, we basically 475 00:29:04,710 --> 00:29:07,820 are programming our brain that can produce a movement 476 00:29:07,820 --> 00:29:10,860 without needing any feedback or anything. 477 00:29:14,110 --> 00:29:17,320 He also studied the optic tract projections 478 00:29:17,320 --> 00:29:23,674 using a stain for degenerating myelin. 479 00:29:23,674 --> 00:29:26,980 Remember what that was? 480 00:29:26,980 --> 00:29:31,906 Nauta used silver stains-- much more sensitive. 481 00:29:31,906 --> 00:29:34,490 It was Markey, the Markey method. 482 00:29:34,490 --> 00:29:37,510 Anyway, Lashley used that and did a pretty accurate job. 483 00:29:37,510 --> 00:29:40,660 He didn't discover the projection of the hypothalamus, 484 00:29:40,660 --> 00:29:43,300 and other very tiny projections of the optic tract. 485 00:29:43,300 --> 00:29:47,820 But he knew the main ones, just from that experimental study. 486 00:29:47,820 --> 00:29:51,780 You remember who Nauta was-- discovered the silver stains 487 00:29:51,780 --> 00:29:54,310 used for the staining degeneration. 488 00:29:57,800 --> 00:30:00,870 And then two more-- Levi-Montalcini and Hans 489 00:30:00,870 --> 00:30:01,370 Kuypers. 490 00:30:01,370 --> 00:30:04,920 Levi-Montalcini discovered what? 491 00:30:04,920 --> 00:30:08,660 She did it with Viktor Hamburger. 492 00:30:08,660 --> 00:30:11,430 They discovered nerve growth factor. 493 00:30:11,430 --> 00:30:15,690 The first of a family of molecules 494 00:30:15,690 --> 00:30:21,140 we call the neurotrophins, the most well-known growth 495 00:30:21,140 --> 00:30:23,820 factors in the nervous systems. 496 00:30:23,820 --> 00:30:29,095 There are other families as well that are not neurotrophins that 497 00:30:29,095 --> 00:30:34,290 have been discovered since, but when you just say nerve growth 498 00:30:34,290 --> 00:30:36,260 factor, you always mean that first one 499 00:30:36,260 --> 00:30:39,675 that Levi-Montalcini and Viktor Hamburger described. 500 00:30:39,675 --> 00:30:42,630 If you just remember her name, that's fine. 501 00:30:42,630 --> 00:30:46,850 She died just recently, at age over 100. 502 00:30:46,850 --> 00:30:50,780 And then Hans Kuypers who, with his student Lawrence, 503 00:30:50,780 --> 00:30:54,630 are well known for their studies of descending pathways, both 504 00:30:54,630 --> 00:31:00,256 their anatomy and their function in primates and monkeys. 505 00:31:03,081 --> 00:31:03,580 OK. 506 00:31:03,580 --> 00:31:06,800 Now, this is the last thing I did. 507 00:31:06,800 --> 00:31:10,050 These are just definitions that you 508 00:31:10,050 --> 00:31:12,400 should go down through this list and see 509 00:31:12,400 --> 00:31:17,210 if you remember all these different words. 510 00:31:17,210 --> 00:31:21,742 Most of them you probably will know. 511 00:31:21,742 --> 00:31:23,880 You should be able to find all of those. 512 00:31:30,520 --> 00:31:33,050 So that's it. 513 00:31:33,050 --> 00:31:39,780 Are there any parts of the class now that you particularly 514 00:31:39,780 --> 00:31:40,762 want to go over? 515 00:31:40,762 --> 00:31:44,240 I can go over any of these. 516 00:31:44,240 --> 00:31:46,200 We've already gone over the answers 517 00:31:46,200 --> 00:31:49,630 to all these questions in the class, 518 00:31:49,630 --> 00:31:56,925 so you can find them by searching your class notes. 519 00:31:59,970 --> 00:32:04,440 Remember, one was the general introduction, 520 00:32:04,440 --> 00:32:06,200 a little bit about glia and method. 521 00:32:09,760 --> 00:32:12,960 I asked the major difference between the tract 522 00:32:12,960 --> 00:32:17,430 tracing methods of Markey and Nauta, 523 00:32:17,430 --> 00:32:20,550 Nauta being more sensitive it didn't 524 00:32:20,550 --> 00:32:24,056 depend on getting myelinated axons. 525 00:32:24,056 --> 00:32:26,320 He did the un-myelinated ones also. 526 00:32:26,320 --> 00:32:29,730 And it was much more sensitive, but not as sensitive 527 00:32:29,730 --> 00:32:31,370 as some of the more recent methods. 528 00:32:31,370 --> 00:32:32,910 What are those more recent methods? 529 00:32:35,820 --> 00:32:42,995 Methods that use axonal transport 530 00:32:42,995 --> 00:32:46,380 in various ways, where you use the transport 531 00:32:46,380 --> 00:32:48,730 mechanism of the axon to inject something 532 00:32:48,730 --> 00:32:49,970 that's still in transport. 533 00:32:49,970 --> 00:32:52,590 It could be a fluorescent molecule. 534 00:32:52,590 --> 00:32:55,670 A lot of them used are fluorescent molecules. 535 00:32:55,670 --> 00:32:57,180 They're very easy to use. 536 00:32:57,180 --> 00:32:59,490 You don't have to use any histochemical technique. 537 00:32:59,490 --> 00:33:00,570 You just inject them. 538 00:33:00,570 --> 00:33:01,940 They're transported on the axon. 539 00:33:01,940 --> 00:33:04,455 And then you just need a good method 540 00:33:04,455 --> 00:33:07,750 of fixing and cutting the brain, and then 541 00:33:07,750 --> 00:33:10,360 looking with a good fluorescent, a very sensitive 542 00:33:10,360 --> 00:33:13,088 fluorescent microscope and look for the fluorescence. 543 00:33:16,230 --> 00:33:19,654 Do any of you remember what diffusion tensor imaging is? 544 00:33:19,654 --> 00:33:20,570 AUDIENCE: [INAUDIBLE]. 545 00:33:24,460 --> 00:33:29,200 PROFESSOR: It uses magnetic resonance imaging, 546 00:33:29,200 --> 00:33:33,470 and the computer's programmed to pay attention 547 00:33:33,470 --> 00:33:35,330 to diffusion of water molecules. 548 00:33:35,330 --> 00:33:36,502 That's right. 549 00:33:36,502 --> 00:33:39,630 And water molecules, when it comes 550 00:33:39,630 --> 00:33:44,490 to these big bundles of axons in the brain, 551 00:33:44,490 --> 00:33:49,920 tends to move down the axon, not across. 552 00:33:49,920 --> 00:33:54,960 And they use that to follow bundles of axons. 553 00:33:54,960 --> 00:33:57,210 And unfortunately, the cognitive psychologists 554 00:33:57,210 --> 00:34:00,820 now think they're studying connections in the brain. 555 00:34:00,820 --> 00:34:03,290 They think we don't need animal work anymore. 556 00:34:03,290 --> 00:34:06,944 We can study connections in the human brain. 557 00:34:06,944 --> 00:34:12,100 I hope you realize how silly that is, because it's not even 558 00:34:12,100 --> 00:34:15,735 as sensitive as the Markey technique, 559 00:34:15,735 --> 00:34:18,010 where it doesn't get connections at all. 560 00:34:18,010 --> 00:34:20,639 But it does give you the position 561 00:34:20,639 --> 00:34:24,240 of the big bundles of axons in the human brain, 562 00:34:24,240 --> 00:34:26,735 or any brain that you use diffusion tensor 563 00:34:26,735 --> 00:34:28,210 imaging to study. 564 00:34:28,210 --> 00:34:30,730 And that's important, because now we can specifically 565 00:34:30,730 --> 00:34:33,780 relate those major pathways in human 566 00:34:33,780 --> 00:34:39,190 to the studies done in monkey and other animals, especially 567 00:34:39,190 --> 00:34:44,954 the primates, because humans are of course one of the primates. 568 00:34:44,954 --> 00:34:49,070 So that's what diffusion tensor imaging is. 569 00:34:49,070 --> 00:34:52,815 I asked for its advantages and its limitations. 570 00:34:52,815 --> 00:34:55,840 Its advantage is you don't have to kill 571 00:34:55,840 --> 00:35:00,840 the animal-- big advantage. 572 00:35:00,840 --> 00:35:04,220 And you can trace major bundles of axons. 573 00:35:04,220 --> 00:35:08,940 Disadvantages-- resolution, you cannot get down to the single 574 00:35:08,940 --> 00:35:13,475 cell level at all, and you cannot trace axons all the way 575 00:35:13,475 --> 00:35:14,309 to connections. 576 00:35:14,309 --> 00:35:16,350 But when you see them coming-- and you don't even 577 00:35:16,350 --> 00:35:21,000 know which direction they're going, major limitation. 578 00:35:21,000 --> 00:35:23,020 But if you see axons coming in and out 579 00:35:23,020 --> 00:35:27,210 of a gyrus in the brain, you can be 580 00:35:27,210 --> 00:35:31,160 pretty sure they're either starting there or ending there, 581 00:35:31,160 --> 00:35:32,910 because they wouldn't go up into the gyrus 582 00:35:32,910 --> 00:35:35,440 and then go out again. 583 00:35:35,440 --> 00:35:39,435 It wouldn't make a lot of sense for them to evolve that way. 584 00:35:39,435 --> 00:35:40,190 All right. 585 00:35:43,310 --> 00:35:45,820 Some of these are just definitions, 586 00:35:45,820 --> 00:35:49,450 like primary sensory neurons and motor neurons, 587 00:35:49,450 --> 00:35:50,690 immediate network neurons. 588 00:36:03,638 --> 00:36:05,740 So you remember the midbrain structure 589 00:36:05,740 --> 00:36:09,690 that's greatly enlarged in predatory [INAUDIBLE] fish? 590 00:36:12,860 --> 00:36:15,870 They're depending a lot on vision for their hunting, 591 00:36:15,870 --> 00:36:19,810 and they don't depend a lot on learning. 592 00:36:19,810 --> 00:36:22,110 So it's the optic tectum. 593 00:36:22,110 --> 00:36:26,640 Unlearned, visually triggered fixed action patters, 594 00:36:26,640 --> 00:36:31,850 used in tectum more than any other structure. 595 00:36:31,850 --> 00:36:35,700 So they orient towards prey animals, 596 00:36:35,700 --> 00:36:40,230 and those neurons are specifically 597 00:36:40,230 --> 00:36:41,830 triggered by the types of movement 598 00:36:41,830 --> 00:36:45,810 that prey animals make. 599 00:36:45,810 --> 00:36:48,170 The frog, another animal-- it's a predator, 600 00:36:48,170 --> 00:36:51,940 it collects insects and worms. 601 00:36:51,940 --> 00:36:54,460 He's got a tectum similarly programmed 602 00:36:54,460 --> 00:36:58,260 to respond to worms and bugs. 603 00:36:58,260 --> 00:37:01,000 If it's a bug moving around like that, 604 00:37:01,000 --> 00:37:05,740 the tectal neurons are buzzing away just like the-- 605 00:37:05,740 --> 00:37:08,890 but the frog just sits there and fixates. 606 00:37:08,890 --> 00:37:13,980 But if that bug stops and he's within range, 607 00:37:13,980 --> 00:37:17,500 then the frog attacks with the flick of his tongue 608 00:37:17,500 --> 00:37:25,170 and grabs the insect, all controlled from the tectum. 609 00:37:25,170 --> 00:37:29,810 What was the major cause of the first three major expansions 610 00:37:29,810 --> 00:37:31,060 of the forebrain in evolution? 611 00:37:34,480 --> 00:37:38,750 That's number one-- started as an olfactory structure, 612 00:37:38,750 --> 00:37:42,860 see it growing out there at the very front of the brain. 613 00:37:42,860 --> 00:37:45,660 And the early cortex was all olfactory. 614 00:37:45,660 --> 00:37:48,540 In most primitive animals, the olfactory bulb 615 00:37:48,540 --> 00:37:52,250 connects to everything in the forebrain. 616 00:37:52,250 --> 00:37:53,390 OK. 617 00:37:53,390 --> 00:37:59,470 Then, what was a later reason that it expanded more? 618 00:37:59,470 --> 00:37:59,970 Sorry? 619 00:37:59,970 --> 00:38:01,390 AUDIENCE: [INAUDIBLE]. 620 00:38:01,390 --> 00:38:05,130 PROFESSOR: Other senses invaded the forebrain. 621 00:38:05,130 --> 00:38:06,880 How did they do that? 622 00:38:06,880 --> 00:38:10,640 Mainly projections from places like the midbrain tectum, 623 00:38:10,640 --> 00:38:12,365 which was very large already. 624 00:38:14,930 --> 00:38:17,360 Any large structure projects all over the place, 625 00:38:17,360 --> 00:38:20,400 and it projected right into the [? tweenbrain, ?] 626 00:38:20,400 --> 00:38:23,980 and the [? tweenbrain ?] connects to the endbrain 627 00:38:23,980 --> 00:38:31,270 structures, both striatum and cortical. 628 00:38:31,270 --> 00:38:37,250 And by invading the striatum, it took 629 00:38:37,250 --> 00:38:40,925 advantage of the kinds of learning that the striatum had 630 00:38:40,925 --> 00:38:46,200 already developed for factory guided behavior. 631 00:38:46,200 --> 00:38:47,610 That's the speculation. 632 00:38:47,610 --> 00:38:50,580 It is very likely to be true. 633 00:38:50,580 --> 00:38:57,754 We know that habits in mammals still depend on those pathways 634 00:38:57,754 --> 00:39:02,020 through the striatum, except that the inputs to the striatum 635 00:39:02,020 --> 00:39:04,435 in advanced mammals becomes more from the cortex. 636 00:39:07,050 --> 00:39:09,070 It doesn't come from the thalamus. 637 00:39:09,070 --> 00:39:11,960 But still, even we have those connections 638 00:39:11,960 --> 00:39:13,830 from the older parts of the thalamus, 639 00:39:13,830 --> 00:39:15,571 right into the striatum. 640 00:39:15,571 --> 00:39:16,070 All right. 641 00:39:16,070 --> 00:39:19,375 And then, the third expansion. 642 00:39:22,700 --> 00:39:23,695 I can't hear you. 643 00:39:23,695 --> 00:39:25,280 AUDIENCE: [INAUDIBLE]. 644 00:39:25,280 --> 00:39:28,050 PROFESSOR: Exactly, with mammals. 645 00:39:28,050 --> 00:39:33,050 The neocortex evolved out of the dorsal cortex, which 646 00:39:33,050 --> 00:39:38,030 was initially-- if you look at the dorsal cortex in reptiles, 647 00:39:38,030 --> 00:39:42,720 for example, it's a parahippocampal area. 648 00:39:42,720 --> 00:39:45,460 And the parahippocampal areas do, in those animals, 649 00:39:45,460 --> 00:39:49,350 get some other sensory inputs. 650 00:39:49,350 --> 00:39:54,920 But the big change was new layers, new types of migration 651 00:39:54,920 --> 00:39:56,450 into the hemisphere. 652 00:39:56,450 --> 00:40:00,330 That led to neocortex, which as we know, 653 00:40:00,330 --> 00:40:02,510 have a lot of advantages for functioning. 654 00:40:02,510 --> 00:40:05,070 It expanded a lot. 655 00:40:05,070 --> 00:40:06,915 So those were the three major expansions. 656 00:40:06,915 --> 00:40:12,190 It didn't lead to the gigantic nature of the human brain. 657 00:40:12,190 --> 00:40:14,460 Well, it did eventually, but there were later 658 00:40:14,460 --> 00:40:17,610 expansions that occurred as well. 659 00:40:17,610 --> 00:40:19,822 There was a late expansion of the association areas, 660 00:40:19,822 --> 00:40:25,696 for example, that led to things like language and other things 661 00:40:25,696 --> 00:40:27,664 that we do with our cortex. 662 00:40:38,000 --> 00:40:39,345 Remember the name cynodont? 663 00:40:42,810 --> 00:40:43,640 You remember. 664 00:40:43,640 --> 00:40:47,030 The mammal-like reptiles, right. 665 00:40:47,030 --> 00:40:51,220 And I used early cynodonts because the late cynodonts 666 00:40:51,220 --> 00:40:53,892 are much more like mammalian brains. 667 00:40:53,892 --> 00:40:57,165 So I wanted something that was more like an amphibian brain, 668 00:40:57,165 --> 00:41:00,050 and the early cynodonts were like that. 669 00:41:00,050 --> 00:41:03,005 But the evolution of those animals is what led to mammals. 670 00:41:07,280 --> 00:41:11,260 So what expanded when neocortex expands? 671 00:41:11,260 --> 00:41:13,170 Animals with really big neocortex, 672 00:41:13,170 --> 00:41:15,530 they have other big things too. 673 00:41:15,530 --> 00:41:18,400 Cerebellum is one. 674 00:41:18,400 --> 00:41:21,726 What projects to the neocortex? 675 00:41:21,726 --> 00:41:23,516 The thalamus. 676 00:41:23,516 --> 00:41:26,680 So the thalamus gets big too. 677 00:41:26,680 --> 00:41:29,100 If cerebellum gets big, what else gets big? 678 00:41:29,100 --> 00:41:34,230 The pons-- gets input from the neocortex and projects 679 00:41:34,230 --> 00:41:36,910 to the cerebellar cortex. 680 00:41:36,910 --> 00:41:37,699 OK. 681 00:41:37,699 --> 00:41:39,240 So you could say any of those things. 682 00:41:41,790 --> 00:41:47,630 Cerebellum, pons, thalamus, they all 683 00:41:47,630 --> 00:41:51,850 get bigger as the neocortex gets bigger. 684 00:41:51,850 --> 00:41:54,250 And if you said something like cerebral peduncle 685 00:41:54,250 --> 00:41:56,970 in the midbrain, that would actually be true too. 686 00:41:56,970 --> 00:41:59,400 They're the axons coming from neocortex 687 00:41:59,400 --> 00:42:02,410 going down to the brain stem, the hindbrain 688 00:42:02,410 --> 00:42:03,290 and the spinal cord. 689 00:42:05,918 --> 00:42:09,020 So you know why the face is not part of the dermatome maps? 690 00:42:13,460 --> 00:42:18,870 Because the dermatomes are areas of the body surface 691 00:42:18,870 --> 00:42:20,397 innervated by what? 692 00:42:20,397 --> 00:42:21,650 AUDIENCE: [INAUDIBLE]. 693 00:42:21,650 --> 00:42:22,650 PROFESSOR: Yes. 694 00:42:22,650 --> 00:42:25,522 And by what going into the spinal cord. 695 00:42:28,500 --> 00:42:33,796 Spinal nerves, the dorsal root of the spinal nerve. 696 00:42:33,796 --> 00:42:35,520 So for every pair of dorsal root, 697 00:42:35,520 --> 00:42:41,320 you have a dermatome, one on either side, actually. 698 00:42:41,320 --> 00:42:44,550 But it doesn't include the face, because that is innervated 699 00:42:44,550 --> 00:42:48,543 by trigeminal nerve, fifth cranial nerve, exactly. 700 00:42:52,980 --> 00:42:57,200 And remember that peculiarity when 701 00:42:57,200 --> 00:42:59,622 we're talking about dorsal column nuclei. 702 00:42:59,622 --> 00:43:02,122 I showed the section through the dorsal column nuclei, 703 00:43:02,122 --> 00:43:05,550 and I said, the whole body surface is represented there. 704 00:43:09,374 --> 00:43:12,840 Nucleus gracilis, the lowest part of the body. 705 00:43:12,840 --> 00:43:17,100 Nucleus cuneatus, the upper part of the body, but not the face. 706 00:43:17,100 --> 00:43:20,010 So how is the face representative? 707 00:43:20,010 --> 00:43:22,140 Descending nucleus of the trigeminal nerve. 708 00:43:25,110 --> 00:43:28,260 The brain stem trigeminal complex, 709 00:43:28,260 --> 00:43:31,360 secondary sensory cells of the trigeminal system, 710 00:43:31,360 --> 00:43:33,140 has a descending nucleus that goes 711 00:43:33,140 --> 00:43:35,520 all the way into the upper part of the spinal cord, 712 00:43:35,520 --> 00:43:38,490 and that's where the face is represented. 713 00:43:38,490 --> 00:43:42,500 And if we have pain in the face, it's 714 00:43:42,500 --> 00:43:45,284 that part in the upper part of the spinal cord that's 715 00:43:45,284 --> 00:43:45,950 being activated. 716 00:43:51,400 --> 00:43:54,220 So what's the oldest descending somatosensory pathway? 717 00:43:57,185 --> 00:43:57,810 Spinoreticular. 718 00:44:01,790 --> 00:44:06,340 In medical school, you'll learn it's the spinothalamic, 719 00:44:06,340 --> 00:44:08,716 because they ignore-- not all medical school. 720 00:44:08,716 --> 00:44:11,272 Some of them talk about spinoreticular also. 721 00:44:16,620 --> 00:44:18,440 Remember the raccoon and the coatimundi? 722 00:44:21,540 --> 00:44:23,550 There's a figure there. 723 00:44:23,550 --> 00:44:27,320 What is the raccoon good at? 724 00:44:27,320 --> 00:44:30,230 Manual dexterity. 725 00:44:30,230 --> 00:44:33,700 He can get in your garbage cans. 726 00:44:33,700 --> 00:44:36,510 The coatimundi can't do that. 727 00:44:36,510 --> 00:44:39,330 So what is different about the somatosensory cortex? 728 00:44:42,960 --> 00:44:48,550 The representation of the digits of his forelimbs, 729 00:44:48,550 --> 00:44:52,080 much bigger in the raccoon-- so big that there's 730 00:44:52,080 --> 00:44:56,210 a separate gyrus for every digit. 731 00:44:56,210 --> 00:45:01,100 The coatimundi's just got a much smaller little area there, 732 00:45:01,100 --> 00:45:04,920 because the surface area of cortex 733 00:45:04,920 --> 00:45:08,140 corresponds basically to dexterity. 734 00:45:08,140 --> 00:45:12,210 The same is true in the motor system, their motor acuity. 735 00:45:12,210 --> 00:45:15,530 You can talk about motor acuity as well as sensory acuity. 736 00:45:29,260 --> 00:45:32,525 I ask you actually to know those four basic cellular events 737 00:45:32,525 --> 00:45:34,680 that Wolpert talks about, because they're all 738 00:45:34,680 --> 00:45:39,280 important in manning developmental processes. 739 00:45:39,280 --> 00:45:41,080 Remember what they were? 740 00:45:41,080 --> 00:45:49,960 Adhesion, contraction, growth, movement. 741 00:45:49,960 --> 00:45:53,190 They interact, of course. 742 00:45:53,190 --> 00:45:55,710 And you can apply them to the growth cone 743 00:45:55,710 --> 00:45:57,852 and explain how axons grow. 744 00:45:57,852 --> 00:46:00,060 Except you also have to know about membrane addition. 745 00:46:13,450 --> 00:46:16,780 Remember the two types of cell division, 746 00:46:16,780 --> 00:46:19,590 symmetric and asymmetric. 747 00:46:19,590 --> 00:46:22,380 Symmetric, they both stay in stem cells. 748 00:46:22,380 --> 00:46:25,206 In asymmetric, one of them migrates away. 749 00:46:25,206 --> 00:46:29,060 The other one keeps dividing. 750 00:46:29,060 --> 00:46:32,020 Lateral horn, you talk about dorsal horn, 751 00:46:32,020 --> 00:46:34,080 ventral horn, the spinal cord. 752 00:46:34,080 --> 00:46:36,090 There's that little bump on the side. 753 00:46:36,090 --> 00:46:38,210 Where's the little bump? 754 00:46:38,210 --> 00:46:42,470 Thoracic and upper lumbar. 755 00:46:42,470 --> 00:46:46,220 Thoracicolumbar or thoracolumbar system, 756 00:46:46,220 --> 00:46:48,300 it's the sympathetic nervous system. 757 00:46:48,300 --> 00:46:50,635 They're the preganglionic motor neurons 758 00:46:50,635 --> 00:46:54,520 of the sympathetic nervous system. 759 00:46:54,520 --> 00:46:56,730 Why are they called motor neurons? 760 00:46:56,730 --> 00:46:59,676 Because the axons leave the cord. 761 00:46:59,676 --> 00:47:03,500 Well, where's the ganglionic motor neuron? 762 00:47:03,500 --> 00:47:06,480 It comes from the sympathetic ganglia, 763 00:47:06,480 --> 00:47:11,740 which are all along the side of the cord, all 764 00:47:11,740 --> 00:47:14,620 the way from the neck, all the way down 765 00:47:14,620 --> 00:47:16,570 to the small of your back. 766 00:47:19,450 --> 00:47:25,170 Plus, a few ganglia that sit out in front, the pre-vertebral, 767 00:47:25,170 --> 00:47:30,430 like the celiac ganglia, more commonly or popularly 768 00:47:30,430 --> 00:47:33,570 known as the solar plexus, because it's 769 00:47:33,570 --> 00:47:37,615 a popular place for a boxer to hit another guy, 770 00:47:37,615 --> 00:47:40,450 in the solar plexus, so he doubles over 771 00:47:40,450 --> 00:47:42,365 and loses control of his guts. 772 00:47:45,818 --> 00:47:48,026 Sorry, but I've got to use some graphic language here 773 00:47:48,026 --> 00:47:51,292 to get you to remember that. 774 00:47:51,292 --> 00:47:54,240 But OK. 775 00:47:54,240 --> 00:47:58,970 If you have trouble and cannot find answers to some of these 776 00:47:58,970 --> 00:48:02,960 things, use the forum. 777 00:48:02,960 --> 00:48:05,140 Because if you don't, I won't answer, 778 00:48:05,140 --> 00:48:11,130 because I want everybody to get the same information. 779 00:48:11,130 --> 00:48:14,790 But you should be able to find answers to all of these, 780 00:48:14,790 --> 00:48:19,870 either in your notes for the class or right in the book. 781 00:48:19,870 --> 00:48:22,140 So I hope that's helpful to you, help 782 00:48:22,140 --> 00:48:23,370 you getting ready for this. 783 00:48:23,370 --> 00:48:26,356 Now you don't have all this uncertainty, 784 00:48:26,356 --> 00:48:28,230 I don't know what's going to be on this exam. 785 00:48:28,230 --> 00:48:31,774 You do know what's going to be on the exam-- this stuff. 786 00:48:31,774 --> 00:48:34,560 AUDIENCE: [INAUDIBLE]. 787 00:48:34,560 --> 00:48:38,330 PROFESSOR: I won't tell you how it's going to be written. 788 00:48:38,330 --> 00:48:40,810 I might change-- for example, just 789 00:48:40,810 --> 00:48:43,460 with these definitions or some of these answers, 790 00:48:43,460 --> 00:48:46,050 I could put matching questions. 791 00:48:46,050 --> 00:48:48,142 But if you know these, you'll certainly 792 00:48:48,142 --> 00:48:49,142 be able to answer those. 793 00:48:59,080 --> 00:49:01,960 All right. 794 00:49:01,960 --> 00:49:05,400 That's the fairest way I know to get you guys ready. 795 00:49:05,400 --> 00:49:08,230 And I wish you all well. 796 00:49:08,230 --> 00:49:09,890 We're not going to meet on Friday, 797 00:49:09,890 --> 00:49:14,310 because I know you are in a hurry to get out of here. 798 00:49:14,310 --> 00:49:17,120 But I will want you to read the chapters 799 00:49:17,120 --> 00:49:20,620 on the chemical senses, taste and olfaction. 800 00:49:20,620 --> 00:49:22,620 I think it's pretty straightforward in the book. 801 00:49:22,620 --> 00:49:24,240 I will answer any questions you have 802 00:49:24,240 --> 00:49:26,730 if you have any about them, so that way 803 00:49:26,730 --> 00:49:30,680 we can get started with the visual system when 804 00:49:30,680 --> 00:49:32,530 you come back.