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 00:00:22,768 --> 00:00:27,190 PROFESSOR: OK, instead of a quiz I'm 9 00:00:27,190 --> 00:00:28,540 trying to write some homework. 10 00:00:28,540 --> 00:00:31,930 And some of them will be extra credit, some of them 11 00:00:31,930 --> 00:00:35,406 will be part of the required homework. 12 00:00:40,790 --> 00:00:54,760 Now today we still have a lot to do on chapter 26 concerning 13 00:00:54,760 --> 00:00:56,900 core pathways of the limbic system. 14 00:00:56,900 --> 00:01:04,709 And this is where we finished last time. 15 00:01:04,709 --> 00:01:07,810 We may not even get to the part on hormones and brain 16 00:01:07,810 --> 00:01:10,860 development and effects on the brain, 17 00:01:10,860 --> 00:01:14,860 but we may just do most of that with the reading 18 00:01:14,860 --> 00:01:19,370 because I really need the time to talk 19 00:01:19,370 --> 00:01:24,570 to you about the recent changes in understanding 20 00:01:24,570 --> 00:01:27,960 of the hippocampus and the pathways related to it. 21 00:01:31,740 --> 00:01:40,680 OK, we answered this question with the information 22 00:01:40,680 --> 00:01:42,860 about the internal environment in the body 23 00:01:42,860 --> 00:01:45,700 reaches the hypothalamus via both the bloodstream 24 00:01:45,700 --> 00:01:48,300 and sensory pathways. 25 00:01:48,300 --> 00:01:50,340 And then I asked this about, well, 26 00:01:50,340 --> 00:01:52,460 how do these molecules even get in the brain? 27 00:01:52,460 --> 00:01:54,550 We know that there's a blood-brain barrier. 28 00:01:57,298 --> 00:02:01,120 Very small molecules can get in, but not the larger, 29 00:02:01,120 --> 00:02:03,270 organic molecules. 30 00:02:03,270 --> 00:02:08,220 And yet, things like angiotensin II do get in, 31 00:02:08,220 --> 00:02:10,680 but they get in only at certain places. 32 00:02:10,680 --> 00:02:14,370 Places where the blood-brain barrier is weak. 33 00:02:14,370 --> 00:02:16,710 I think the figure in the book is a little better 34 00:02:16,710 --> 00:02:20,240 than this one, but this is a similar one. 35 00:02:20,240 --> 00:02:24,224 It just shows the site from the walls 36 00:02:24,224 --> 00:02:25,640 of the third and fourth ventricles 37 00:02:25,640 --> 00:02:27,920 where the brain barrier is lacking, 38 00:02:27,920 --> 00:02:30,540 and the ones you hear about here, 39 00:02:30,540 --> 00:02:34,150 mainly we talked very early about the area postrema 40 00:02:34,150 --> 00:02:37,765 where toxins in the blood can get in and elicit vomiting. 41 00:02:40,734 --> 00:02:45,850 The subfornical organ has a weak blood-brain barrier, 42 00:02:45,850 --> 00:02:52,310 and the median eminence of the hypothalamus. 43 00:02:52,310 --> 00:02:54,350 And that's where I want to look now just 44 00:02:54,350 --> 00:02:58,140 to show you an experiment on the blood-brain barrier. 45 00:02:58,140 --> 00:03:01,520 This is where, with injection of horseradish peroxidase-- 46 00:03:01,520 --> 00:03:05,466 which is a tracer because it's transported 47 00:03:05,466 --> 00:03:08,310 both anterogradely and retrogradely in axons-- 48 00:03:08,310 --> 00:03:14,710 but if you just put it in the bloodstream, not in the brain, 49 00:03:14,710 --> 00:03:17,020 it doesn't get in the brain everywhere, 50 00:03:17,020 --> 00:03:22,390 just where the blood-brain barrier is weak. 51 00:03:22,390 --> 00:03:27,270 And so here we are at the base of the third ventricle. 52 00:03:27,270 --> 00:03:30,590 So we're in the hypothalamic region. 53 00:03:30,590 --> 00:03:33,740 This region is called the median eminence. 54 00:03:33,740 --> 00:03:37,380 It's near the stalk of the pituitary. 55 00:03:37,380 --> 00:03:43,020 And most of the hypothalamus here and, of course, 56 00:03:43,020 --> 00:03:46,700 thalamus and other areas that you can't see here, 57 00:03:46,700 --> 00:03:49,710 you see the HRP in the blood. 58 00:03:49,710 --> 00:03:51,590 So it's in the capillaries. 59 00:03:51,590 --> 00:03:56,110 These are all little capillaries in some larger vessels. 60 00:03:56,110 --> 00:03:59,290 It's always, with this particular method, 61 00:03:59,290 --> 00:04:02,450 it's showing us bright white. 62 00:04:02,450 --> 00:04:05,770 But look at the median eminence. 63 00:04:05,770 --> 00:04:11,889 The HRP pervades the tissue in the median eminence. 64 00:04:11,889 --> 00:04:13,305 And that's the kind of experiments 65 00:04:13,305 --> 00:04:17,230 that have been done now in a number of different animals 66 00:04:17,230 --> 00:04:21,850 to show these areas. 67 00:04:21,850 --> 00:04:28,830 And in those areas there's always receptors-- in neurons, 68 00:04:28,830 --> 00:04:33,590 generally-- that respond to specific things-- 69 00:04:33,590 --> 00:04:38,510 like angiotensin, for example, and other things. 70 00:04:38,510 --> 00:04:42,300 Here in the median eminence you would have sexual hormones, 71 00:04:42,300 --> 00:04:45,070 for example, secreted by the gonads that 72 00:04:45,070 --> 00:04:51,840 can affect the brain by getting in this route. 73 00:04:51,840 --> 00:04:53,105 Now what about sensory inputs? 74 00:04:55,630 --> 00:04:57,830 Well, we know the vagus nerve carries 75 00:04:57,830 --> 00:05:03,230 inputs about pain, temperature, stomach distention, 76 00:05:03,230 --> 00:05:05,250 other visceral inputs. 77 00:05:05,250 --> 00:05:14,350 And there's also inputs coming from the sacral region, 78 00:05:14,350 --> 00:05:19,210 including inputs from the genital region and basically 79 00:05:19,210 --> 00:05:19,980 the lower viscera. 80 00:05:23,470 --> 00:05:24,970 But there are other pathways that 81 00:05:24,970 --> 00:05:26,820 just come in through the dorsal roots. 82 00:05:26,820 --> 00:05:29,480 Pathways carrying pain information, for example. 83 00:05:29,480 --> 00:05:33,120 And this is an interesting one because pain information 84 00:05:33,120 --> 00:05:36,850 can reach the hypothalamus directly 85 00:05:36,850 --> 00:05:40,040 from secondary sensory neurons and tertiary sensory neurons 86 00:05:40,040 --> 00:05:41,460 in the spinal cord. 87 00:05:41,460 --> 00:05:44,270 So it comes directly from dorsal horn. 88 00:05:44,270 --> 00:05:47,190 There are long pathways that do reach the hypothalamus. 89 00:05:50,650 --> 00:05:52,520 It's the lemniscal pathway that I 90 00:05:52,520 --> 00:05:56,590 don't think I mentioned-- it's not a real large one but it 91 00:05:56,590 --> 00:06:02,660 does exist, and could be very important in responses to pain. 92 00:06:02,660 --> 00:06:07,200 We know that pain elicits activation 93 00:06:07,200 --> 00:06:10,530 of the sympathetic nervous system and results 94 00:06:10,530 --> 00:06:16,930 in inhibition of most parasympathetic functions, 95 00:06:16,930 --> 00:06:19,340 and it does so very quickly through this pathway. 96 00:06:26,950 --> 00:06:36,900 OK, then there's inputs from neurons in the hypothalamus 97 00:06:36,900 --> 00:06:42,520 that respond to temperature, or to the osmolarity of the blood. 98 00:06:46,360 --> 00:06:48,827 If you record for most neurons-- I 99 00:06:48,827 --> 00:06:54,420 may have mentioned this when we talked about regulation 100 00:06:54,420 --> 00:06:58,470 of the internal environment before-- but these neurons 101 00:06:58,470 --> 00:07:00,940 change their firing in very precise ways 102 00:07:00,940 --> 00:07:03,730 with the temperature. 103 00:07:03,730 --> 00:07:07,640 It's obviously pretty important for the brain 104 00:07:07,640 --> 00:07:10,690 to get that information and it's going to control temperature 105 00:07:10,690 --> 00:07:11,615 regulating mechanisms. 106 00:07:15,560 --> 00:07:19,370 They're in the anterior hypothalamic region. 107 00:07:19,370 --> 00:07:21,860 And then we know there's some olfactory inputs that 108 00:07:21,860 --> 00:07:23,060 reach pretty directly. 109 00:07:23,060 --> 00:07:27,286 In fact, many more animals, the olfactory bulbs 110 00:07:27,286 --> 00:07:28,910 project directly into the hypothalamus. 111 00:07:32,440 --> 00:07:39,300 But they project indirectly there in all the vertebrates. 112 00:07:39,300 --> 00:07:44,660 And we know the retina projects directly to the hypothalamus. 113 00:07:44,660 --> 00:07:46,835 Mainly to the suprachiasmatic nucleus 114 00:07:46,835 --> 00:07:48,855 where we have the biological clock mechanism, 115 00:07:48,855 --> 00:07:51,510 but there's other regions too that 116 00:07:51,510 --> 00:07:55,210 get sparser inputs from the retina. 117 00:07:55,210 --> 00:07:59,400 We talked about that in chapter 20. 118 00:08:04,030 --> 00:08:07,280 OK, now I want to start talking about some 119 00:08:07,280 --> 00:08:14,140 of the circuitry that links the hypothalamus to endbrain 120 00:08:14,140 --> 00:08:20,350 structures, the limbic endbrain structures. 121 00:08:20,350 --> 00:08:25,340 And these studies were given a lot of impetus 122 00:08:25,340 --> 00:08:28,730 by James Papez, a neuroanatomist working 123 00:08:28,730 --> 00:08:35,039 at Cornell in the 1930s. 124 00:08:35,039 --> 00:08:38,610 And there's been a big revival of interest in that circuit. 125 00:08:38,610 --> 00:08:41,590 I mean, there are a few neuroanatomy texts 126 00:08:41,590 --> 00:08:43,070 for medical schools that don't even 127 00:08:43,070 --> 00:08:47,390 mention James Papez anymore, but that's 128 00:08:47,390 --> 00:08:53,320 because they're not keeping up with all the recent interest in 129 00:08:53,320 --> 00:08:56,250 and research labs in some of these pathways. 130 00:08:56,250 --> 00:08:58,170 So I want to go through them. 131 00:08:58,170 --> 00:09:00,720 So we talk about Papez circuit, which is interesting 132 00:09:00,720 --> 00:09:03,050 because it's a complete circuit. 133 00:09:07,200 --> 00:09:08,837 You can start at any point, but if you 134 00:09:08,837 --> 00:09:10,470 go to the cingulate cortex, we know 135 00:09:10,470 --> 00:09:14,400 that cingulate is one of the paralimbic areas that 136 00:09:14,400 --> 00:09:19,100 sends projections to hippocampal, parahippocampal 137 00:09:19,100 --> 00:09:23,730 regions, which then project directly into the hippocampus. 138 00:09:23,730 --> 00:09:28,180 And the hippocampus then projects 139 00:09:28,180 --> 00:09:32,130 to subcortical regions through the fornix. 140 00:09:32,130 --> 00:09:33,490 A major output. 141 00:09:33,490 --> 00:09:36,440 Not the only output, but it's the major output 142 00:09:36,440 --> 00:09:39,070 going subcortically. 143 00:09:39,070 --> 00:09:42,000 It goes to the septal area, but it continues. 144 00:09:42,000 --> 00:09:46,810 Long axons continue right to the hypothalamus. 145 00:09:46,810 --> 00:09:49,329 Most of them terminate in the mammillary bodies 146 00:09:49,329 --> 00:09:51,120 at the very caudal end of the hypothalamus. 147 00:09:53,890 --> 00:09:58,030 And those structures project to the thalamus-- 148 00:09:58,030 --> 00:10:01,435 the anterior nuclei-- which connects to cingulate cortex. 149 00:10:01,435 --> 00:10:03,550 So it forms, then, a complete loop. 150 00:10:06,390 --> 00:10:10,330 So Papez published this paper in 1937. 151 00:10:10,330 --> 00:10:14,770 It was called "The Proposed Mechanism of Emotion." 152 00:10:14,770 --> 00:10:17,410 And basically he argued that people 153 00:10:17,410 --> 00:10:21,850 had associated a group of structures 154 00:10:21,850 --> 00:10:28,500 in the forebrain-- especially the endbrain-- with olfaction. 155 00:10:28,500 --> 00:10:31,910 And he said they weren't really olfactory in humans 156 00:10:31,910 --> 00:10:35,000 because the clinical information-- and he reviewed 157 00:10:35,000 --> 00:10:38,340 a lot of it-- indicates that they're really 158 00:10:38,340 --> 00:10:42,170 involved in emotion, emotional expression, 159 00:10:42,170 --> 00:10:52,250 emotional disturbances, and the feelings accompanying emotions. 160 00:10:52,250 --> 00:10:56,365 And he also noted one other thing 161 00:10:56,365 --> 00:10:59,650 that people often forget about. 162 00:10:59,650 --> 00:11:01,370 They have a low threshold for seizures, 163 00:11:01,370 --> 00:11:04,390 so seizures that tend to start in one of these structures 164 00:11:04,390 --> 00:11:07,470 will spread through all of them because they're 165 00:11:07,470 --> 00:11:10,120 closely interconnected, which was one of his arguments. 166 00:11:10,120 --> 00:11:15,350 Remember, he didn't have the precise neuroanatomical methods 167 00:11:15,350 --> 00:11:17,300 that we have now. 168 00:11:17,300 --> 00:11:19,180 And believe me, diffusion tensor imaging 169 00:11:19,180 --> 00:11:22,655 is not going to give you these connections adequately. 170 00:11:22,655 --> 00:11:27,680 It'll tell you the main tracks, but it's not useful for this. 171 00:11:27,680 --> 00:11:31,025 You need good anatomical techniques 172 00:11:31,025 --> 00:11:34,430 where you can use animals to do experiments and trace 173 00:11:34,430 --> 00:11:38,390 connections to synaptic endings. 174 00:11:38,390 --> 00:11:41,140 But Papez was remarkably accurate 175 00:11:41,140 --> 00:11:48,325 in his basic description of the circuit based on clinical work. 176 00:11:51,650 --> 00:11:55,060 But now we can take that original circuit of his 177 00:11:55,060 --> 00:12:01,400 and expand it a little bit from more recent studies 178 00:12:01,400 --> 00:12:05,095 using experimental neuroanatomical techniques 179 00:12:05,095 --> 00:12:07,570 of the Nauta type, OK? 180 00:12:07,570 --> 00:12:09,190 And many people that are followed now 181 00:12:09,190 --> 00:12:11,766 with various kinds of tract tracing techniques. 182 00:12:16,660 --> 00:12:18,540 I should also point out here that it 183 00:12:18,540 --> 00:12:23,070 was during this time after Papez that the term "limbic system" 184 00:12:23,070 --> 00:12:29,810 was coined, based on Broca's term, the great limbic lobe. 185 00:12:29,810 --> 00:12:31,830 In modern times, it was Paul MacLean 186 00:12:31,830 --> 00:12:36,610 at the National Institute of Health, a colleague of Nauta's, 187 00:12:36,610 --> 00:12:42,040 that actually coined that term, the limbic system. 188 00:12:42,040 --> 00:12:45,520 And Nauta then extended it into the midbrain, 189 00:12:45,520 --> 00:12:47,920 and did a number of studies of connections 190 00:12:47,920 --> 00:12:49,760 of that system in the endbrain. 191 00:12:52,890 --> 00:12:55,830 But I'll focus on the way our understanding of the system 192 00:12:55,830 --> 00:12:56,660 has changed. 193 00:12:56,660 --> 00:13:00,900 It won't sound like we're discussing mechanisms 194 00:13:00,900 --> 00:13:06,100 of emotion for the most part, but we will get to that also. 195 00:13:06,100 --> 00:13:07,250 OK. 196 00:13:07,250 --> 00:13:10,330 The reason there's such a revival of interest, of course, 197 00:13:10,330 --> 00:13:12,660 is because of the involvement of the hippocampus 198 00:13:12,660 --> 00:13:16,860 in long-term memory formation and what 199 00:13:16,860 --> 00:13:19,260 we call episodic memory-- not habit formation, 200 00:13:19,260 --> 00:13:25,130 not striatal memory which we've mentioned a number of times, 201 00:13:25,130 --> 00:13:28,380 but the kind of memory that we usually mean when we say, 202 00:13:28,380 --> 00:13:29,450 I remember something. 203 00:13:29,450 --> 00:13:31,390 Yes, I remember something, something happened. 204 00:13:31,390 --> 00:13:34,830 I remember something that happened over there. 205 00:13:34,830 --> 00:13:36,980 That's what we're talking about here. 206 00:13:36,980 --> 00:13:40,720 And that certainly adds to the importance of understanding 207 00:13:40,720 --> 00:13:42,365 these circuits and how they work. 208 00:13:42,365 --> 00:13:44,320 Now if you look at a medical school text, 209 00:13:44,320 --> 00:13:47,280 you're likely to see something like this. 210 00:13:47,280 --> 00:13:51,560 Just to show you, it can be really difficult 211 00:13:51,560 --> 00:13:54,030 because they only give you human brain. 212 00:13:54,030 --> 00:13:55,785 So I'm not going to do that. 213 00:13:55,785 --> 00:13:58,200 I won't expect you to understand it 214 00:13:58,200 --> 00:14:01,870 once you begin to understand the circuitry. 215 00:14:01,870 --> 00:14:05,681 So we're going to take our diagram here 216 00:14:05,681 --> 00:14:08,140 of the mammalian brain. 217 00:14:08,140 --> 00:14:12,590 Let's take this one and turn it around like this. 218 00:14:12,590 --> 00:14:17,115 And now let's just slice off the hemispheres like this. 219 00:14:17,115 --> 00:14:24,070 OK, we'll throw this one away, and turn this on its side 220 00:14:24,070 --> 00:14:25,390 so we get this. 221 00:14:25,390 --> 00:14:27,920 Here's the hemisphere up here, and here's the brainstem down 222 00:14:27,920 --> 00:14:30,480 here. 223 00:14:30,480 --> 00:14:33,400 We're looking at it from the side showing 224 00:14:33,400 --> 00:14:36,406 where a few of the pathways are. 225 00:14:36,406 --> 00:14:38,990 So we've made the brain transparent. 226 00:14:38,990 --> 00:14:40,950 And the same here in the hemisphere 227 00:14:40,950 --> 00:14:43,770 where I've shown the hippocampus there. 228 00:14:48,000 --> 00:14:51,830 And now I want to know how-- this 229 00:14:51,830 --> 00:14:55,470 was the original figure here-- I want to show you 230 00:14:55,470 --> 00:14:57,590 where you get Papez circuit in that. 231 00:14:57,590 --> 00:14:59,440 Very straightforward. 232 00:14:59,440 --> 00:15:00,100 OK? 233 00:15:00,100 --> 00:15:03,420 So let's start this time with the mammillary bodies. 234 00:15:03,420 --> 00:15:06,300 Here we are at the caudal end of the hypothalamus. 235 00:15:06,300 --> 00:15:09,570 The mammillary bodies project by a very direct route. 236 00:15:09,570 --> 00:15:12,100 We always see this in cross sections 237 00:15:12,100 --> 00:15:15,120 here in the diencephalon. 238 00:15:15,120 --> 00:15:20,350 Trace the mammillothalamic tract to the anterior nucelei. 239 00:15:20,350 --> 00:15:22,300 There's three main nuclei that project 240 00:15:22,300 --> 00:15:25,650 to various parts of the cingulate cortex. 241 00:15:25,650 --> 00:15:29,530 They follow a route to the cortex through what 242 00:15:29,530 --> 00:15:31,715 we call the anterior thalamic radiations. 243 00:15:31,715 --> 00:15:35,515 They don't go out the side like, say, the geniculate bodies do. 244 00:15:35,515 --> 00:15:45,340 They go forward and then course just above the corpus collosum, 245 00:15:45,340 --> 00:15:48,000 throughout the entire length of the corpus collosum, 246 00:15:48,000 --> 00:15:50,760 terminating in the cingulate cortex 247 00:15:50,760 --> 00:15:52,010 at all these different levels. 248 00:15:52,010 --> 00:15:54,150 And terminating also in the area just 249 00:15:54,150 --> 00:15:57,660 behind the collosum in an area we 250 00:15:57,660 --> 00:16:00,880 call the retrosplenial area, meaning 251 00:16:00,880 --> 00:16:04,470 behind the splenium of the corpus callosum. 252 00:16:04,470 --> 00:16:08,020 That's the caudal end of the corpus collosum. 253 00:16:08,020 --> 00:16:11,560 Anterior end is the genu, the caudal end 254 00:16:11,560 --> 00:16:15,630 is the splenium because of its shape in humans. 255 00:16:18,720 --> 00:16:23,760 And cingulate and these other parahippocampal areas, 256 00:16:23,760 --> 00:16:25,860 including the entorhinal cortex which 257 00:16:25,860 --> 00:16:27,670 gets heavy input from the cingulate 258 00:16:27,670 --> 00:16:29,410 and retrosplenial areas. 259 00:16:29,410 --> 00:16:31,924 They project directly into the hippocampal formation. 260 00:16:34,590 --> 00:16:37,010 And then here's the output of the hippocampus, 261 00:16:37,010 --> 00:16:40,030 through this thick column of fibers 262 00:16:40,030 --> 00:16:43,460 that courses just in through the caudal end of the septum 263 00:16:43,460 --> 00:16:46,340 in front of the thalamus. 264 00:16:46,340 --> 00:16:48,660 And then, because I've separated it here, 265 00:16:48,660 --> 00:16:51,680 I pick it up again right here. 266 00:16:51,680 --> 00:16:54,130 There's the fornix columns coming 267 00:16:54,130 --> 00:16:56,600 through the hypothalamus. 268 00:16:56,600 --> 00:16:59,460 There are some axons that terminate on the way, 269 00:16:59,460 --> 00:17:03,220 but most of them are ending there on the mammillary bodies. 270 00:17:03,220 --> 00:17:04,250 OK. 271 00:17:04,250 --> 00:17:13,960 So now let's take that circuit and see how-- I mean, 272 00:17:13,960 --> 00:17:15,609 just the circuit, what good is that? 273 00:17:15,609 --> 00:17:17,609 You've got to know, well, what's coming into it, 274 00:17:17,609 --> 00:17:20,349 what's coming out of it, and what purpose, 275 00:17:20,349 --> 00:17:23,000 what kind of information does it carry? 276 00:17:23,000 --> 00:17:30,510 And there, initially anatomy was way ahead of the physiology. 277 00:17:30,510 --> 00:17:33,420 Within the anatomy was done well enough 278 00:17:33,420 --> 00:17:37,870 that physiologists had better guides and they started doing 279 00:17:37,870 --> 00:17:39,290 different kinds of study. 280 00:17:39,290 --> 00:17:43,200 So I'm going to talk about some physiology here. 281 00:17:43,200 --> 00:17:46,350 OK, so here's a diagram. 282 00:17:46,350 --> 00:17:49,660 A more up-to-date version of Papez circuit. 283 00:17:49,660 --> 00:17:55,140 And I've shown in red those structures that Papez named 284 00:17:55,140 --> 00:17:58,030 for human-- mammillary bodies, anterior 285 00:17:58,030 --> 00:18:05,530 nuclei, cingulate cortex, the hippocampal formation. 286 00:18:05,530 --> 00:18:10,440 These are the major components. 287 00:18:10,440 --> 00:18:14,180 Subiculum and hippocampus are one line of cells, 288 00:18:14,180 --> 00:18:16,104 and the dentate gyrus. 289 00:18:16,104 --> 00:18:17,520 And then we're going to be looking 290 00:18:17,520 --> 00:18:21,710 at that very soon in a little more detail. 291 00:18:21,710 --> 00:18:24,390 And then there's that output, the fornix. 292 00:18:24,390 --> 00:18:27,970 And notice that there's a less direct route that 293 00:18:27,970 --> 00:18:33,430 goes through the septal area to the hypothalamus as well. 294 00:18:33,430 --> 00:18:35,780 So I've included all that here, and I've 295 00:18:35,780 --> 00:18:38,470 included some accents that go in the reverse direction. 296 00:18:38,470 --> 00:18:39,910 And I've shown that many of these, 297 00:18:39,910 --> 00:18:41,975 in fact, are two-way connections. 298 00:18:44,510 --> 00:18:48,420 As like most cortex, it gets input from the thalamus. 299 00:18:48,420 --> 00:18:51,628 Those cortical areas project back to the thalamus too. 300 00:18:56,400 --> 00:19:03,630 OK, and I ask here in this question 301 00:19:03,630 --> 00:19:06,500 how's it connected to neocortical areas. 302 00:19:06,500 --> 00:19:08,720 Well, look right here. 303 00:19:08,720 --> 00:19:11,400 See, this wasn't discussed so much by Papez, 304 00:19:11,400 --> 00:19:16,920 but we know that these cingulate areas 305 00:19:16,920 --> 00:19:20,610 and other paralimbic areas-- like the entorhinal area-- 306 00:19:20,610 --> 00:19:23,210 are closely connected to neocortex. 307 00:19:23,210 --> 00:19:26,850 They get major inputs from association areas, 308 00:19:26,850 --> 00:19:28,800 not from primary sensory areas. 309 00:19:28,800 --> 00:19:32,290 They're not getting it from visual cortex or auditory 310 00:19:32,290 --> 00:19:34,400 cortex or somatosensory cortex. 311 00:19:34,400 --> 00:19:36,770 They're getting it from association areas, 312 00:19:36,770 --> 00:19:41,130 particularly from the multimodal association areas. 313 00:19:41,130 --> 00:19:43,050 OK? 314 00:19:43,050 --> 00:19:46,990 It's an interesting thing, those multimodal association areas 315 00:19:46,990 --> 00:19:48,680 are like the most primitive cortex, 316 00:19:48,680 --> 00:19:50,920 but they are the areas that have expanded 317 00:19:50,920 --> 00:19:53,710 the most in recent evolution. 318 00:19:53,710 --> 00:19:56,050 And they're getting major inputs from 319 00:19:56,050 --> 00:19:59,055 the unimodal sensory areas. 320 00:20:02,210 --> 00:20:05,060 They get their input from primary sensory areas. 321 00:20:05,060 --> 00:20:05,920 OK. 322 00:20:05,920 --> 00:20:10,150 So the association areas then connect into Papez circuit 323 00:20:10,150 --> 00:20:15,100 through these routes I'm showing-- through cingulate, 324 00:20:15,100 --> 00:20:18,960 retrosplenial, and entorhinal areas-- which 325 00:20:18,960 --> 00:20:22,090 then project directly into the cortex. 326 00:20:22,090 --> 00:20:25,760 There's more than one route there, 327 00:20:25,760 --> 00:20:29,300 I just indicate a couple of them. 328 00:20:29,300 --> 00:20:37,510 OK, so what is going on this route here? 329 00:20:37,510 --> 00:20:41,370 What is the mammillary body telling the cingulate cortex 330 00:20:41,370 --> 00:20:42,080 and hippocampus? 331 00:20:45,300 --> 00:20:47,555 It concerns our sense of direction. 332 00:20:51,480 --> 00:20:53,470 And it's a big surprise for many people 333 00:20:53,470 --> 00:20:56,365 because we were thinking all the time in terms of Papez 334 00:20:56,365 --> 00:20:59,570 and emotion, all this, but you'll 335 00:20:59,570 --> 00:21:02,625 see how, in fact, it doesn't [INAUDIBLE]. 336 00:21:05,610 --> 00:21:07,980 Where does our sense of direction in the world 337 00:21:07,980 --> 00:21:10,930 come from? 338 00:21:10,930 --> 00:21:14,360 How do you know where you are? 339 00:21:14,360 --> 00:21:15,690 So you're taking a walk. 340 00:21:18,436 --> 00:21:21,060 It's a little harder to think of when you're inside a building, 341 00:21:21,060 --> 00:21:23,360 but really not that much. 342 00:21:23,360 --> 00:21:24,920 But think of an animal walking. 343 00:21:24,920 --> 00:21:27,040 He always has a sense of direction. 344 00:21:27,040 --> 00:21:29,760 When he doesn't, we say he's disoriented. 345 00:21:29,760 --> 00:21:33,580 When we feel very disoriented, well, what happens? 346 00:21:33,580 --> 00:21:36,640 When we lose the landmarks we were depending on? 347 00:21:36,640 --> 00:21:41,090 And for primates and many other animals, it's primarily visual. 348 00:21:41,090 --> 00:21:43,630 Even a rat-- not such a visual animal, 349 00:21:43,630 --> 00:21:46,260 but yet his major landmarks are still visual. 350 00:21:46,260 --> 00:21:48,111 That's how he knows where he is. 351 00:21:51,480 --> 00:21:57,020 And that's usually detected by cortex, a neocortex. 352 00:22:00,390 --> 00:22:03,120 So we know what direction we're going with respect 353 00:22:03,120 --> 00:22:04,850 to landmarks, even when we're not 354 00:22:04,850 --> 00:22:08,070 really aware of which landmarks we're using. 355 00:22:08,070 --> 00:22:08,570 OK? 356 00:22:14,190 --> 00:22:19,640 That head direction, with respect to landmarks, 357 00:22:19,640 --> 00:22:24,110 is you can call it allocentric head direction. 358 00:22:24,110 --> 00:22:27,750 If I want to know where that object is with respect 359 00:22:27,750 --> 00:22:30,090 to my head, that's not what I'm talking about here. 360 00:22:30,090 --> 00:22:31,390 That's egocentric. 361 00:22:31,390 --> 00:22:34,420 That has to do with where it is with respect to my head 362 00:22:34,420 --> 00:22:35,870 and eyes. 363 00:22:35,870 --> 00:22:37,850 Now I'm talking about where we are 364 00:22:37,850 --> 00:22:41,630 with respect to some landmark. 365 00:22:41,630 --> 00:22:44,170 I know where I am here with respect to the doors, 366 00:22:44,170 --> 00:22:47,740 with respect to the status center, things like that. 367 00:22:53,990 --> 00:22:56,670 That's allocentric head direction. 368 00:22:56,670 --> 00:22:59,300 But that's changing all the time, 369 00:22:59,300 --> 00:23:01,970 I'm moving my head around. 370 00:23:01,970 --> 00:23:04,790 An animal is moving his head around. 371 00:23:04,790 --> 00:23:09,450 OK, he's got a wonderful system for taking those changes 372 00:23:09,450 --> 00:23:16,260 in head direction and affecting the activity that's 373 00:23:16,260 --> 00:23:19,740 being sent by hippocampus down to the mammillary bodies, 374 00:23:19,740 --> 00:23:24,670 and correcting it for changes in head direction. 375 00:23:24,670 --> 00:23:27,066 That's what's happening there in the mammillary bodies. 376 00:23:32,790 --> 00:23:35,910 So from moment to moment, the signal 377 00:23:35,910 --> 00:23:38,550 going from mammillary bodies back 378 00:23:38,550 --> 00:23:45,640 to the cingulate and hippocampus is always 379 00:23:45,640 --> 00:23:50,372 corrected for the momentary head direction. 380 00:23:50,372 --> 00:23:51,780 So it's constantly changing. 381 00:23:51,780 --> 00:23:54,180 That's why it's so important. 382 00:23:54,180 --> 00:23:55,420 Why is that so important? 383 00:23:58,180 --> 00:24:04,380 Because the way my head is pointed is, potentially, 384 00:24:04,380 --> 00:24:07,150 where I can go. 385 00:24:07,150 --> 00:24:10,490 Think of an animal foraging. 386 00:24:10,490 --> 00:24:12,010 He can turn this way and that. 387 00:24:15,200 --> 00:24:17,410 What is important for him to know? 388 00:24:17,410 --> 00:24:21,170 What's important for him to know is what's in front of him. 389 00:24:21,170 --> 00:24:26,070 And he remembers things that are in front of him. 390 00:24:26,070 --> 00:24:31,220 He has a map of the environment that he's learned. 391 00:24:31,220 --> 00:24:40,800 So all the time, the hippocampus is connected through the cortex 392 00:24:40,800 --> 00:24:43,367 and is activating these memories of things 393 00:24:43,367 --> 00:24:44,575 that happened in those areas. 394 00:24:44,575 --> 00:24:47,910 So he knows, am I going towards a good area or a bad area? 395 00:24:47,910 --> 00:24:50,340 We know, are we going towards food or not food? 396 00:24:50,340 --> 00:24:53,580 Are we going towards our friends or not towards our friends? 397 00:24:53,580 --> 00:24:55,850 Are we going to our classroom or not? 398 00:24:58,354 --> 00:24:59,770 So you begin to see the connection 399 00:24:59,770 --> 00:25:01,680 of the circuit with memory now. 400 00:25:09,340 --> 00:25:11,790 So how does that change in head direction work? 401 00:25:11,790 --> 00:25:14,300 Let's go back to the Papez circuit here. 402 00:25:14,300 --> 00:25:16,750 Well, here's the mammillary bodies 403 00:25:16,750 --> 00:25:20,170 and they're getting input from these structures-- 404 00:25:20,170 --> 00:25:22,350 the caudal end of the midbrain. 405 00:25:22,350 --> 00:25:24,450 Some books say the rostral hindbrain, 406 00:25:24,450 --> 00:25:26,024 but they're right at the caudal end 407 00:25:26,024 --> 00:25:28,510 of the midbrain in most books. 408 00:25:28,510 --> 00:25:31,630 OK, then the tegmental nuclei of Gudden. 409 00:25:31,630 --> 00:25:32,130 OK. 410 00:25:32,130 --> 00:25:36,000 And they carry information derived mainly 411 00:25:36,000 --> 00:25:37,730 from the vestibular sense-- probably 412 00:25:37,730 --> 00:25:43,580 from proprioception as well-- about any change 413 00:25:43,580 --> 00:25:45,320 in the direction of the head. 414 00:25:48,796 --> 00:25:49,296 All right. 415 00:26:00,230 --> 00:26:02,660 You can record head directions and you 416 00:26:02,660 --> 00:26:05,940 find them parallel on that circuit. 417 00:26:05,940 --> 00:26:07,500 So the information they're carrying 418 00:26:07,500 --> 00:26:10,690 is always is corrected; it's changing 419 00:26:10,690 --> 00:26:14,609 every time the animal moves its head. 420 00:26:14,609 --> 00:26:15,650 Well, there's other ways. 421 00:26:15,650 --> 00:26:18,560 We know we've moved our head not just from vestibular sense; 422 00:26:18,560 --> 00:26:20,770 we also know it from vision. 423 00:26:20,770 --> 00:26:27,150 So I put in here-- lateral shifts in head direction 424 00:26:27,150 --> 00:26:31,780 do excite cells in the pretectal area. 425 00:26:31,780 --> 00:26:32,740 OK. 426 00:26:32,740 --> 00:26:35,250 And there's a pathway from the pretectal area that 427 00:26:35,250 --> 00:26:39,140 goes to this nucleus, the lateral dorsal nucleus which 428 00:26:39,140 --> 00:26:43,720 sits right next to the anterior nuclei. 429 00:26:43,720 --> 00:26:46,610 So I put that in here because they're carrying head direction 430 00:26:46,610 --> 00:26:49,820 information to the lateral dorsal nucleus, 431 00:26:49,820 --> 00:26:53,140 and it's a system completely parallel 432 00:26:53,140 --> 00:26:59,280 to the mammillary body to anterior nucleus pathway. 433 00:26:59,280 --> 00:27:02,260 So you're getting changes in head direction coming 434 00:27:02,260 --> 00:27:08,490 into the lateral dorsal nucleus which also gets projections 435 00:27:08,490 --> 00:27:11,400 from hippocampal formation. 436 00:27:11,400 --> 00:27:13,550 So in both places, you're constantly 437 00:27:13,550 --> 00:27:17,540 correcting that information about where 438 00:27:17,540 --> 00:27:19,340 we are with respect to landmarks. 439 00:27:19,340 --> 00:27:23,049 We're correcting it for changes in head direction. 440 00:27:23,049 --> 00:27:25,215 I know this makes it seem a little more complicated, 441 00:27:25,215 --> 00:27:29,616 but this is the simpler diagram here. 442 00:27:29,616 --> 00:27:32,140 You can just remember there's a parallel pathway there 443 00:27:32,140 --> 00:27:33,365 for visual information. 444 00:27:41,070 --> 00:27:45,100 I want to point out that the axons in Papez circuit 445 00:27:45,100 --> 00:27:46,710 are more than one type. 446 00:27:46,710 --> 00:27:48,480 And the ones signaling head direction 447 00:27:48,480 --> 00:27:52,830 are the ones that physiologists have characterized the best. 448 00:27:52,830 --> 00:27:55,270 We often don't know what the others do, 449 00:27:55,270 --> 00:27:57,170 but it's a large number. 450 00:27:57,170 --> 00:27:59,920 A lot of the axons in the mammillothalamic tract 451 00:27:59,920 --> 00:28:02,164 are involved in this. 452 00:28:02,164 --> 00:28:03,580 I don't want to give you the sense 453 00:28:03,580 --> 00:28:05,030 that we know everything about it, 454 00:28:05,030 --> 00:28:12,626 but we do know about a major component of it. 455 00:28:12,626 --> 00:28:15,230 We also know the hippocampus-- through the fornix-- 456 00:28:15,230 --> 00:28:17,425 is sending information to other areas 457 00:28:17,425 --> 00:28:18,970 than just the mammillary bodies. 458 00:28:21,650 --> 00:28:25,340 It may be altering motivations, motivational level, 459 00:28:25,340 --> 00:28:27,810 according to what you're facing. 460 00:28:34,060 --> 00:28:35,694 We know it more from what it might 461 00:28:35,694 --> 00:28:37,235 be doing from behavioral work than we 462 00:28:37,235 --> 00:28:40,091 do from anatomical and physiological work. 463 00:28:40,091 --> 00:28:40,590 OK. 464 00:28:40,590 --> 00:28:42,980 A few other terms here-- you should 465 00:28:42,980 --> 00:28:45,380 know what the basal forebrain is. 466 00:28:45,380 --> 00:28:48,510 And if I go back to this picture-- 467 00:28:48,510 --> 00:28:51,570 when you talk about basal forebrain, 468 00:28:51,570 --> 00:28:55,240 if you look at the bottom one here, here's hypothalamus. 469 00:28:55,240 --> 00:28:59,650 It's a little bit arbitrary where hypothalamus ends here. 470 00:28:59,650 --> 00:29:04,545 We say it ends about-- if this is the optic chiasm, where 471 00:29:04,545 --> 00:29:09,100 the optic tract is crossing, the areas in front 472 00:29:09,100 --> 00:29:11,850 of the optic chiasm are basal forebrain. 473 00:29:15,900 --> 00:29:18,740 If you look at sections-- let's look 474 00:29:18,740 --> 00:29:23,090 at these sections for a minute-- and start back here with things 475 00:29:23,090 --> 00:29:24,660 we've studied before. 476 00:29:24,660 --> 00:29:26,940 Here's the midbrain section, there's 477 00:29:26,940 --> 00:29:29,810 the central gray, and the ventral tegmental area, 478 00:29:29,810 --> 00:29:32,320 goes to the limbic midbrain areas. 479 00:29:32,320 --> 00:29:36,760 When you follow these forward, both central gray and ventral 480 00:29:36,760 --> 00:29:40,582 tegmental area are continuous with hypothalamus. 481 00:29:40,582 --> 00:29:43,110 You follow either of them forward 482 00:29:43,110 --> 00:29:44,832 and you come right into hypothalamus, 483 00:29:44,832 --> 00:29:46,050 posterior hypothalamus. 484 00:29:46,050 --> 00:29:49,640 So here we are in the middle of the hypothalamus, 485 00:29:49,640 --> 00:29:53,959 forming the ventral part of the tween brain. 486 00:29:53,959 --> 00:29:55,500 Here we are a little further forward. 487 00:29:55,500 --> 00:30:00,760 You see the optic tract now just behind the chiasm. 488 00:30:00,760 --> 00:30:05,635 The fornix fibers are a bundle at the medial edge 489 00:30:05,635 --> 00:30:09,800 of the medial forebrain bundle there, which basically courses 490 00:30:09,800 --> 00:30:13,110 through the whole lateral hypothalamus. 491 00:30:13,110 --> 00:30:22,500 But then you go forward, and when the thalamus stops, 492 00:30:22,500 --> 00:30:26,270 now there's the hemispheres with the septum in between. 493 00:30:26,270 --> 00:30:29,130 The septal area-- in humans it's very thin, 494 00:30:29,130 --> 00:30:33,540 but in rats and other rodents it's very thick. 495 00:30:33,540 --> 00:30:36,885 This is basal forebrain at the bottom. 496 00:30:36,885 --> 00:30:40,710 The olfactory tubercle, that's the ventral-most part 497 00:30:40,710 --> 00:30:43,730 of the striata, the part that's been there 498 00:30:43,730 --> 00:30:47,110 since the most ancient chordates. 499 00:30:47,110 --> 00:30:51,205 Getting the olfactory input and that's 500 00:30:51,205 --> 00:30:56,520 how olfaction originally and still influences behavior, 501 00:30:56,520 --> 00:31:00,060 by projecting into this region. 502 00:31:00,060 --> 00:31:04,620 But notice other things in that region. 503 00:31:04,620 --> 00:31:07,240 If you go back a little bit you're in amygdala. 504 00:31:12,050 --> 00:31:20,430 And this node here, that the whole ventral medial striatum 505 00:31:20,430 --> 00:31:24,780 is, I've got it called here the same way as the basal forebrain 506 00:31:24,780 --> 00:31:27,320 because, in fact, they are all part of the ventral striatum. 507 00:31:30,110 --> 00:31:32,350 Usually we don't say the septum's part 508 00:31:32,350 --> 00:31:38,560 of this striatum because of it's embryonic origins, 509 00:31:38,560 --> 00:31:40,530 but the rest of these structures are 510 00:31:40,530 --> 00:31:41,840 all part of ventral striatum. 511 00:31:41,840 --> 00:31:44,360 And if we go forward, where now it 512 00:31:44,360 --> 00:31:49,720 divides into two hemispheres, you can follow it. 513 00:31:49,720 --> 00:31:54,080 This is still our basal forebrain, that is the septum, 514 00:31:54,080 --> 00:31:58,920 and includes the most ventral medial part of it 515 00:31:58,920 --> 00:32:04,390 of the striatum here. 516 00:32:04,390 --> 00:32:08,585 Most of this we call ventral striatum. 517 00:32:08,585 --> 00:32:14,910 And it has specific structures in it, like nucleus accumbens, 518 00:32:14,910 --> 00:32:19,180 bed nucleus of the stria terminalis, 519 00:32:19,180 --> 00:32:22,290 the basal nucleus of Meynert, and so forth. 520 00:32:22,290 --> 00:32:23,730 All right. 521 00:32:23,730 --> 00:32:25,657 It's nice to review these a little bit. 522 00:32:25,657 --> 00:32:26,740 I've not named everything. 523 00:32:30,770 --> 00:32:32,720 Let's talk about a couple of other things 524 00:32:32,720 --> 00:32:39,270 here quickly that you should understand a little bit. 525 00:32:39,270 --> 00:32:42,080 I'm interested in ways the hypothalamus can 526 00:32:42,080 --> 00:32:44,432 influence the neocortex. 527 00:32:44,432 --> 00:32:46,890 And I want you to remember the major reward 528 00:32:46,890 --> 00:32:49,330 pathway in mammalian CNS. 529 00:32:49,330 --> 00:32:50,850 Can someone answer that? 530 00:32:50,850 --> 00:32:55,730 What's the major reward pathway, if you hear that phrase? 531 00:32:55,730 --> 00:32:57,505 We've known about it for many years. 532 00:33:00,370 --> 00:33:03,800 These are the axons that use dopamine as a transmitter. 533 00:33:03,800 --> 00:33:04,970 Where they coming from? 534 00:33:07,650 --> 00:33:09,470 Here, when you talk about the ones coming 535 00:33:09,470 --> 00:33:13,260 from the ventral tegmental area here, OK. 536 00:33:13,260 --> 00:33:16,030 But in fact, the function of the ones that come from the nigra 537 00:33:16,030 --> 00:33:21,510 here-- the medial part of the nigra here 538 00:33:21,510 --> 00:33:26,790 perhaps should be shaded in pink here too because it's really 539 00:33:26,790 --> 00:33:29,290 part of the limbic system as well. 540 00:33:29,290 --> 00:33:31,265 They're really also a reward pathway, 541 00:33:31,265 --> 00:33:33,300 but of a different nature. 542 00:33:33,300 --> 00:33:38,280 Usually we're talking about the dopamine axons that 543 00:33:38,280 --> 00:33:41,045 go through the medial forebrain bundle 544 00:33:41,045 --> 00:33:45,180 in the lateral hypothalamus here, and project 545 00:33:45,180 --> 00:33:46,566 into the basal forebrain. 546 00:34:00,240 --> 00:34:02,800 So what about this first one? 547 00:34:02,800 --> 00:34:04,540 Describe two ways the hypothalamus 548 00:34:04,540 --> 00:34:05,775 can influence the neocortex. 549 00:34:05,775 --> 00:34:08,570 Well actually, there's a lot of ways. 550 00:34:08,570 --> 00:34:12,750 You could say, well, the hypothalamus 551 00:34:12,750 --> 00:34:17,230 is connected in a two-directional way 552 00:34:17,230 --> 00:34:23,630 with limbic structures, subcortical limbic structures. 553 00:34:23,630 --> 00:34:27,719 And those are connected with, you could say, 554 00:34:27,719 --> 00:34:32,090 cortical and limbic structures including hippocampus, 555 00:34:32,090 --> 00:34:34,520 which are connected to the paralimbic areas, which 556 00:34:34,520 --> 00:34:38,130 are connected to the neocortical areas. 557 00:34:38,130 --> 00:34:43,980 This is [INAUDIBLE] diagram, it shows just major routes 558 00:34:43,980 --> 00:34:46,959 from sensory areas. 559 00:34:46,959 --> 00:34:49,690 This is primary sensory areas here, 560 00:34:49,690 --> 00:34:51,346 the hypothalamus down here. 561 00:34:54,870 --> 00:34:57,775 First of all, we do expect the hypothalamus 562 00:34:57,775 --> 00:34:59,355 to influence neocortical area. 563 00:34:59,355 --> 00:35:04,120 And what kind of influence are we talking about? 564 00:35:04,120 --> 00:35:06,330 Well, you know what functions the hypothalamus 565 00:35:06,330 --> 00:35:09,605 is involved in, so we're talking about influences 566 00:35:09,605 --> 00:35:13,730 of the mood, motivational states, 567 00:35:13,730 --> 00:35:16,400 and neocortical processes. 568 00:35:16,400 --> 00:35:20,880 And we know that moods, and especially motivational states, 569 00:35:20,880 --> 00:35:22,800 influence the way decisions are being 570 00:35:22,800 --> 00:35:26,380 made by neocortical systems. 571 00:35:31,350 --> 00:35:34,860 We may be talking about cognitive functions 572 00:35:34,860 --> 00:35:39,160 but you don't get away from motivation. 573 00:35:39,160 --> 00:35:41,820 You don't behave without motivation, 574 00:35:41,820 --> 00:35:51,480 and motivation often involves changes in emotional states 575 00:35:51,480 --> 00:35:53,080 as well. 576 00:35:53,080 --> 00:35:54,030 All right. 577 00:35:54,030 --> 00:35:58,400 So here I outlined many different ways 578 00:35:58,400 --> 00:36:00,630 the hypothalamus can influence the neocortex. 579 00:36:03,640 --> 00:36:05,692 We just talked about Papez circuit. 580 00:36:05,692 --> 00:36:08,810 The more direct and the more indirect way through Papez 581 00:36:08,810 --> 00:36:14,550 circuit to get from hypothalamus to neocortex. 582 00:36:14,550 --> 00:36:17,630 Earlier we talked about the gating of information 583 00:36:17,630 --> 00:36:19,615 by hypothalamus, the gating of information 584 00:36:19,615 --> 00:36:21,190 going through the thalamus. 585 00:36:21,190 --> 00:36:23,730 These are the chapters where I mention that. 586 00:36:23,730 --> 00:36:25,926 That's certainly a way the hypothalamus 587 00:36:25,926 --> 00:36:28,880 is influencing neocortex. 588 00:36:28,880 --> 00:36:31,885 We talked in chapter 17 about the widespread external 589 00:36:31,885 --> 00:36:32,385 systems. 590 00:36:36,790 --> 00:36:40,010 I mention a few of them here again. 591 00:36:40,010 --> 00:36:42,700 That's certainly an influence of hypothalamus from neocortex. 592 00:36:45,960 --> 00:36:49,310 But then there's a very direct way, 593 00:36:49,310 --> 00:36:53,600 by way of the medial dorsal nucleus, and I show it here. 594 00:36:53,600 --> 00:36:55,400 Here's your hypothalamus down here. 595 00:36:55,400 --> 00:36:57,200 Here's the thalamus, and I'm showing here 596 00:36:57,200 --> 00:36:59,770 the medial dorsal nucleus which begets 597 00:36:59,770 --> 00:37:01,420 prefrontal areas of the cortex. 598 00:37:01,420 --> 00:37:05,280 And the medial part, which contains the larger cells, 599 00:37:05,280 --> 00:37:07,640 receives axons-- I've just shown them here 600 00:37:07,640 --> 00:37:13,160 on the left with a red arrow-- the hypothalamus projects 601 00:37:13,160 --> 00:37:17,440 as does olfactory system to that part 602 00:37:17,440 --> 00:37:18,995 of the medial dorsal nucleus. 603 00:37:22,180 --> 00:37:25,715 So this is probably the most direct way 604 00:37:25,715 --> 00:37:29,150 hypothalamus can influence the neocortex. 605 00:37:29,150 --> 00:37:33,820 But all those inmost direct ways are very important as well. 606 00:37:33,820 --> 00:37:36,275 The influence is very widespread. 607 00:37:39,010 --> 00:37:39,510 OK. 608 00:37:44,310 --> 00:37:47,290 So I point out here that a person's mental state 609 00:37:47,290 --> 00:37:49,820 can influence the endocrine organs 610 00:37:49,820 --> 00:37:51,070 by way of the hypothalamus. 611 00:37:54,430 --> 00:37:57,010 You've got to consider what we mean by mental state. 612 00:38:00,780 --> 00:38:02,710 Let's talk about how the hypothalamus 613 00:38:02,710 --> 00:38:04,865 can influence that mental state. 614 00:38:07,870 --> 00:38:12,550 The influences go in both directions. 615 00:38:12,550 --> 00:38:16,500 So that's one way they get experimental data on it 616 00:38:16,500 --> 00:38:19,560 is to look at disturbances of the hypothalamus 617 00:38:19,560 --> 00:38:22,830 during neurosurgical procedures, because often 618 00:38:22,830 --> 00:38:28,200 during neurosurgical procedures, the patient is conscious. 619 00:38:28,200 --> 00:38:30,643 The brain doesn't contain pain receptors 620 00:38:30,643 --> 00:38:34,570 and pain pathways don't originate in the brain itself, 621 00:38:34,570 --> 00:38:36,440 so you can operate on the brain as long 622 00:38:36,440 --> 00:38:39,201 you anesthetize the structures that you 623 00:38:39,201 --> 00:38:42,700 have to open up to get in. 624 00:38:42,700 --> 00:38:48,090 OK, so you can get pretty drastic changes 625 00:38:48,090 --> 00:38:52,510 in autonomic activity, you can get changes in mood, 626 00:38:52,510 --> 00:38:55,090 changes in emotional expression, changes 627 00:38:55,090 --> 00:38:56,560 in feelings being reported. 628 00:38:59,480 --> 00:39:02,560 The founder of our department, [INAUDIBLE] 629 00:39:02,560 --> 00:39:06,610 always in his introductory lectures-- in 900-- 630 00:39:06,610 --> 00:39:12,710 would talk about a soldier during World War 631 00:39:12,710 --> 00:39:18,740 II who ended up with a piece of shrapnel 632 00:39:18,740 --> 00:39:19,830 in his third ventricle. 633 00:39:24,290 --> 00:39:28,130 Very difficult, at that time anyway, to get it out, 634 00:39:28,130 --> 00:39:30,830 so they left it there. 635 00:39:30,830 --> 00:39:36,870 Every time he moved his head a lot, that piece of shrapnel 636 00:39:36,870 --> 00:39:40,170 would ride around inside his third ventricle 637 00:39:40,170 --> 00:39:42,640 and stimulate structures mechanically 638 00:39:42,640 --> 00:39:45,510 near the walls of the ventricle. 639 00:39:45,510 --> 00:39:48,300 And he would start crying uncontrollably. 640 00:39:50,806 --> 00:39:53,500 And it's only when he sat still for a while 641 00:39:53,500 --> 00:39:54,910 that that stimulation stopped. 642 00:39:57,710 --> 00:40:02,630 What interested me the most is that when you asked him 643 00:40:02,630 --> 00:40:05,510 why he was crying, he would say things like, 644 00:40:05,510 --> 00:40:07,609 well, it cries in me. 645 00:40:07,609 --> 00:40:09,150 In other words, that's not me crying, 646 00:40:09,150 --> 00:40:12,110 it's just something happening to me. 647 00:40:12,110 --> 00:40:15,000 But later as time went on, he began 648 00:40:15,000 --> 00:40:19,760 identifying with his states and he would say, 649 00:40:19,760 --> 00:40:24,372 I feel really sad and unhappy and that's why I'm crying. 650 00:40:24,372 --> 00:40:26,816 And I think that's a real lesson. 651 00:40:26,816 --> 00:40:30,260 When things happen to us you don't really 652 00:40:30,260 --> 00:40:31,765 have to identify with the states, 653 00:40:31,765 --> 00:40:33,715 you can separate yourself from them. 654 00:40:33,715 --> 00:40:36,480 And that is the way you have more self-control. 655 00:40:41,120 --> 00:40:44,310 Nauta goes on and he talks about the concepts 656 00:40:44,310 --> 00:40:46,770 of autonomic and voluntary. 657 00:40:46,770 --> 00:40:48,985 We talk about the voluntary nervous system 658 00:40:48,985 --> 00:40:51,775 for the primal tract, for example. 659 00:40:51,775 --> 00:40:53,840 It's part of the voluntary nervous system. 660 00:40:56,510 --> 00:41:01,620 We talk about the involuntary nervous system, 661 00:41:01,620 --> 00:41:08,640 the autonomic nervous system, and other subcortical or non 662 00:41:08,640 --> 00:41:12,570 extrapyramidal motor system, like involving 663 00:41:12,570 --> 00:41:16,722 cerebellum and striatum, and various structures 664 00:41:16,722 --> 00:41:17,430 of the brainstem. 665 00:41:21,360 --> 00:41:24,200 And Nauta pointed out that that's a little bit misleading 666 00:41:24,200 --> 00:41:31,360 because, first of all, the so called 667 00:41:31,360 --> 00:41:34,120 voluntary nervous system-- corticospinal projections 668 00:41:34,120 --> 00:41:39,840 and so forth-- are engaged in unconscious habits, performance 669 00:41:39,840 --> 00:41:43,570 of habits that you can do with very little awareness. 670 00:41:46,450 --> 00:41:49,410 It's not just voluntary movements. 671 00:41:49,410 --> 00:41:51,200 I'm just pointing out that we don't fully 672 00:41:51,200 --> 00:41:52,880 understand what we mean when we talk 673 00:41:52,880 --> 00:41:57,840 about voluntary and involuntary in terms of brain structures. 674 00:41:57,840 --> 00:42:03,090 Similar to autonomic, it's usually 675 00:42:03,090 --> 00:42:06,660 things happening automatically, but in fact, some people 676 00:42:06,660 --> 00:42:09,444 get quite a bit of control out of their autonomic nervous 677 00:42:09,444 --> 00:42:11,240 system. 678 00:42:11,240 --> 00:42:16,030 The best known is reported yogic exercises 679 00:42:16,030 --> 00:42:18,240 where people learn to control their heart rate, 680 00:42:18,240 --> 00:42:20,340 they can even change their body temperature. 681 00:42:20,340 --> 00:42:23,240 There's even some yogis that are able to make one hand 682 00:42:23,240 --> 00:42:26,860 warmer than the other, and things like that. 683 00:42:26,860 --> 00:42:28,930 But I point out here that it's very limited 684 00:42:28,930 --> 00:42:35,550 because most people can't do those things at all, at least 685 00:42:35,550 --> 00:42:38,010 not directly. 686 00:42:38,010 --> 00:42:41,450 Nauta also points out that hypothalamus 687 00:42:41,450 --> 00:42:45,700 has very few long pathways either leading out of it 688 00:42:45,700 --> 00:42:46,880 or coming into it. 689 00:42:46,880 --> 00:42:50,760 I mentioned the long pathway carrying pain information, 690 00:42:50,760 --> 00:42:51,890 but that's very unusual. 691 00:42:51,890 --> 00:42:55,930 Most of them are polysynaptic unlike pyramidal tract, 692 00:42:55,930 --> 00:42:58,810 unlike the dorsal column medial lemniscus 693 00:42:58,810 --> 00:43:02,140 system which are long accents. 694 00:43:02,140 --> 00:43:04,760 Characteristic of hypothalamic connections 695 00:43:04,760 --> 00:43:06,426 are the shorter pathways. 696 00:43:12,030 --> 00:43:16,510 One more topic here that you should know about. 697 00:43:16,510 --> 00:43:19,220 We talked about disconnecting hypothalamus 698 00:43:19,220 --> 00:43:20,690 from other structures. 699 00:43:20,690 --> 00:43:22,510 It was a very interesting experiment 700 00:43:22,510 --> 00:43:26,010 I did not talk about when we talked about those earlier 701 00:43:26,010 --> 00:43:27,050 experiments. 702 00:43:27,050 --> 00:43:28,950 That's particularly interesting to me 703 00:43:28,950 --> 00:43:32,165 because I'm interested in mechanisms for recovery. 704 00:43:32,165 --> 00:43:34,490 And I talked about diaschisis effects, 705 00:43:34,490 --> 00:43:36,530 well this involves that. 706 00:43:36,530 --> 00:43:42,910 If you take a rabbit, and you can loop a wire-- 707 00:43:42,910 --> 00:43:44,760 it's a difficult surgical procedure, 708 00:43:44,760 --> 00:43:47,720 but you can get a wire in there that loops 709 00:43:47,720 --> 00:43:53,130 below the caudal end of the hypothalamus. 710 00:43:53,130 --> 00:43:56,805 So if the wire is pulled-- so now that animal's conscious, 711 00:43:56,805 --> 00:44:01,610 but he's got that wire-- so you can pull the wire 712 00:44:01,610 --> 00:44:05,110 and you're not causing any pain, but you're basically 713 00:44:05,110 --> 00:44:09,690 slicing the pathways between the hypothalamus and midbrain. 714 00:44:13,160 --> 00:44:15,240 And if you pull it up high enough, 715 00:44:15,240 --> 00:44:19,380 you'll completely disconnect the hypothalamus from the midbrain. 716 00:44:19,380 --> 00:44:23,300 OK, if you do that in one quick step, 717 00:44:23,300 --> 00:44:25,910 you will have a lot of trouble keeping that animal alive 718 00:44:25,910 --> 00:44:29,080 because he can't directly control 719 00:44:29,080 --> 00:44:32,160 his feeding, his temperature, and various things 720 00:44:32,160 --> 00:44:35,160 like that that the hypothalamus is so important for. 721 00:44:35,160 --> 00:44:41,200 But if you do it in small steps, and wait 722 00:44:41,200 --> 00:44:43,820 every time you do a little more damage, 723 00:44:43,820 --> 00:44:45,340 you wait-- he will recover. 724 00:44:49,840 --> 00:44:53,930 And if you keep doing it, you'll eventually completely separate 725 00:44:53,930 --> 00:44:58,160 the hypothalamus from the midbrain, 726 00:44:58,160 --> 00:45:01,430 and he still recovers. 727 00:45:01,430 --> 00:45:03,430 That's called a multi-stage lesion. 728 00:45:03,430 --> 00:45:06,030 What kind of damage to the brain can you 729 00:45:06,030 --> 00:45:10,860 think of that's like that in patients? 730 00:45:10,860 --> 00:45:15,360 Think of a tumor that's slow growing. 731 00:45:15,360 --> 00:45:17,390 One reason they're so difficult to detect 732 00:45:17,390 --> 00:45:20,590 and one reason a person will come to see the doctor only 733 00:45:20,590 --> 00:45:23,990 when it's huge is because it's like that wire being pulled 734 00:45:23,990 --> 00:45:26,820 really slowly he's recovering all 735 00:45:26,820 --> 00:45:29,358 the time from the damage being done. 736 00:45:29,358 --> 00:45:29,858 [INAUDIBLE]? 737 00:45:34,240 --> 00:45:37,950 That's one reason why people with Alzheimer's or people 738 00:45:37,950 --> 00:45:42,880 with Parkinson's, say, you don't notice the symptoms 739 00:45:42,880 --> 00:45:46,550 until the damage is very far along because it's 740 00:45:46,550 --> 00:45:49,590 happening gradually. 741 00:45:49,590 --> 00:45:51,700 It's a good parallel. 742 00:45:51,700 --> 00:45:53,740 All right. 743 00:45:53,740 --> 00:45:56,799 So that's Rudolph Powell was the one who 744 00:45:56,799 --> 00:46:01,528 did that with rabbits, that experiment 745 00:46:01,528 --> 00:46:02,962 I was just describing. 746 00:46:06,750 --> 00:46:10,220 I just point out some of the things you should review, 747 00:46:10,220 --> 00:46:14,030 and I also showed the figure from a paper that 748 00:46:14,030 --> 00:46:22,380 studied how the central gray area of the midbrain, 749 00:46:22,380 --> 00:46:26,570 especially in an animal that's got this kind of disconnection, 750 00:46:26,570 --> 00:46:29,860 actually has different areas that serve, 751 00:46:29,860 --> 00:46:37,010 say, fight and flight, sexual behavior, defensive behavior, 752 00:46:37,010 --> 00:46:38,280 and even feeding. 753 00:46:41,240 --> 00:46:45,890 So it is possible for animals to recover a lot. 754 00:46:45,890 --> 00:46:49,140 The problem is if the midbrain-- they don't 755 00:46:49,140 --> 00:46:50,890 have much control of the endbrain at all, 756 00:46:50,890 --> 00:46:53,140 so they're completely abnormal and they will not 757 00:46:53,140 --> 00:46:55,900 initiate very much behavior, as we said before. 758 00:46:59,300 --> 00:47:00,780 So that's one of my favorite quotes 759 00:47:00,780 --> 00:47:03,800 from Rumi, when we're studying hypothalamus, 760 00:47:03,800 --> 00:47:06,570 this is the way I feel. 761 00:47:06,570 --> 00:47:12,490 OK, so I will post the slides here 762 00:47:12,490 --> 00:47:15,470 that discuss hormonal and other influences. 763 00:47:15,470 --> 00:47:17,820 We'll spend just a little time at the beginning 764 00:47:17,820 --> 00:47:22,340 of the next class going over just a few things here. 765 00:47:22,340 --> 00:47:25,280 I think it's a very interesting topic and I know all of you 766 00:47:25,280 --> 00:47:27,220 are interested in it. 767 00:47:27,220 --> 00:47:34,470 But read chapter 27, and then we'll go to chapter 28 768 00:47:34,470 --> 00:47:38,330 because I need at least a full class 769 00:47:38,330 --> 00:47:40,200 to talk about hippocampus, so we'll 770 00:47:40,200 --> 00:47:43,355 do that in the second part of the next class. 771 00:47:43,355 --> 00:47:47,160 And then that's Friday, and then on Monday we'll 772 00:47:47,160 --> 00:47:48,720 finish talking about hippocampus, 773 00:47:48,720 --> 00:47:50,720 so we can talk about the amygdala 774 00:47:50,720 --> 00:47:53,160 and the basal forebrain.