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 00:00:22,737 --> 00:00:23,320 PROFESSOR: OK. 9 00:00:23,320 --> 00:00:26,746 Today we want to focus just on the hippocampal formation. 10 00:00:29,280 --> 00:00:31,330 These are a couple terms I want to make 11 00:00:31,330 --> 00:00:36,140 sure you're understanding the way I've been using them. 12 00:00:36,140 --> 00:00:38,110 Whenever we talk about the limbic system, 13 00:00:38,110 --> 00:00:40,430 we're talking about structures closely connected 14 00:00:40,430 --> 00:00:45,180 to the hypothalamus, so similarly in the endbrain. 15 00:00:45,180 --> 00:00:48,835 The limbic telencephalon always means the endbrain structure 16 00:00:48,835 --> 00:00:51,090 is strongly connected to the hypothalamus. 17 00:00:51,090 --> 00:00:53,820 It doesn't mean they're not interconnected. 18 00:00:53,820 --> 00:00:55,580 They usually are. 19 00:00:55,580 --> 00:00:57,574 But what they have most in common 20 00:00:57,574 --> 00:00:59,365 is their connections with the hypothalamus. 21 00:01:02,830 --> 00:01:06,890 And when we use the term pallium it always 22 00:01:06,890 --> 00:01:10,080 means-- the word means a cloak or mantle, so 23 00:01:10,080 --> 00:01:13,730 similar to the meaning of cortex means bark. 24 00:01:13,730 --> 00:01:15,820 The bark of a tree is a cortex. 25 00:01:18,460 --> 00:01:22,290 So all the cortical structures of the endbrain are included. 26 00:01:22,290 --> 00:01:25,920 And the medial pallium includes the hippocampus. 27 00:01:29,160 --> 00:01:34,320 The medial pallium of the embryo, 28 00:01:34,320 --> 00:01:41,000 it's still called medial pallium in many non mammalian animals. 29 00:01:44,310 --> 00:01:46,800 When we talk about basal forebrain-- 30 00:01:46,800 --> 00:01:50,260 and we'll talk more about that when 31 00:01:50,260 --> 00:01:56,390 we talk about amygdala too-- we don't talk about-- we 32 00:01:56,390 --> 00:01:57,750 don't call it the pallium. 33 00:01:57,750 --> 00:02:00,760 Even at the base there were the olfactory tubercle 34 00:02:00,760 --> 00:02:03,710 is somewhat cortical-like, we just 35 00:02:03,710 --> 00:02:07,850 call it the basal forebrain of parts of the ventral striatum. 36 00:02:07,850 --> 00:02:13,550 You'll see that in the way I label the pictures. 37 00:02:13,550 --> 00:02:15,390 And these are the functional topics 38 00:02:15,390 --> 00:02:16,990 we'll be paying attention to. 39 00:02:16,990 --> 00:02:21,970 Spatial memory, place cells and head direction cells. 40 00:02:21,970 --> 00:02:26,960 We'll talk a little bit about synaptic change, especially 41 00:02:26,960 --> 00:02:29,270 synaptic enhancement and information storage 42 00:02:29,270 --> 00:02:31,330 in the hippocampus. 43 00:02:31,330 --> 00:02:34,490 And a little bit about some of the neurotransmitters 44 00:02:34,490 --> 00:02:38,120 involved, especially acetylcholine and the way 45 00:02:38,120 --> 00:02:44,430 they changed, for example, in sleep compared to waking. 46 00:02:44,430 --> 00:02:45,540 All right. 47 00:02:45,540 --> 00:02:50,270 So first of all, you need to know differences between place 48 00:02:50,270 --> 00:02:54,070 cells and head direction cells. 49 00:02:54,070 --> 00:02:55,979 How are such cells defined? 50 00:02:55,979 --> 00:02:57,895 Well, they're defined by electrophysiologists. 51 00:03:00,890 --> 00:03:05,760 And this is a point, as I did for the auditory system 52 00:03:05,760 --> 00:03:08,030 also, if I wanted to talk about function 53 00:03:08,030 --> 00:03:11,010 I had to refer to physiological studies as well 54 00:03:11,010 --> 00:03:12,770 as anatomical studies. 55 00:03:12,770 --> 00:03:15,950 In fact, I can't make sense of the anatomical pathways 56 00:03:15,950 --> 00:03:19,620 without that physiological information, as well as 57 00:03:19,620 --> 00:03:22,950 some information from ablation studies of behavior. 58 00:03:26,910 --> 00:03:30,330 So we knew about place cells long 59 00:03:30,330 --> 00:03:32,620 before we knew about head direction cells. 60 00:03:32,620 --> 00:03:35,960 But it was only when work on head direction cells 61 00:03:35,960 --> 00:03:41,780 began to appear-- less than two decades ago-- that we began 62 00:03:41,780 --> 00:03:44,125 understand more about these pathways. 63 00:03:47,690 --> 00:03:51,510 So we'll learn about the pathways 64 00:03:51,510 --> 00:03:54,650 whereby the shifts in head direction 65 00:03:54,650 --> 00:03:58,830 are signaled to the endbrain and hippocampus 66 00:03:58,830 --> 00:04:02,030 and why that's important. 67 00:04:02,030 --> 00:04:05,290 And when we talk about place cells, 68 00:04:05,290 --> 00:04:08,400 I will try to remember-- I'm not sure 69 00:04:08,400 --> 00:04:10,750 if I answered these questions in the slides, 70 00:04:10,750 --> 00:04:14,130 but I'll try to remember to do it, but it is in the book-- 71 00:04:14,130 --> 00:04:17,170 the differences between dorsal and ventral hippocampuses. 72 00:04:17,170 --> 00:04:18,200 It's quite important. 73 00:04:18,200 --> 00:04:20,779 Basic differences that, in the more ventral 74 00:04:20,779 --> 00:04:23,630 hippocampus-- which in humans is the more anterior 75 00:04:23,630 --> 00:04:26,230 hippocampus because of the shift of hippocampus 76 00:04:26,230 --> 00:04:30,220 into the temporal lobe-- the connections to the amygdala 77 00:04:30,220 --> 00:04:31,420 are strong. 78 00:04:31,420 --> 00:04:34,010 Not true for the dorsal hippocampus. 79 00:04:34,010 --> 00:04:38,280 And the place cells represent larger places 80 00:04:38,280 --> 00:04:40,690 than in the dorsal hippocampus. 81 00:04:40,690 --> 00:04:44,660 So this is an illustration of physiological-- 82 00:04:44,660 --> 00:04:49,280 from a physiological study of place cells 83 00:04:49,280 --> 00:04:52,520 where they record from a number of different neurons 84 00:04:52,520 --> 00:04:54,160 in the hippocampal formation. 85 00:04:54,160 --> 00:04:57,800 Usually they're recording from dorsal hippocampus 86 00:04:57,800 --> 00:05:02,240 because, when we say dorsal and ventral 87 00:05:02,240 --> 00:05:06,260 we're usually talking about a rat or a mouse or a hamster-- 88 00:05:06,260 --> 00:05:08,090 usually it's rats and mice that are 89 00:05:08,090 --> 00:05:12,070 used in these studies-- each of these little squares 90 00:05:12,070 --> 00:05:16,320 represents a room where the rat can run around. 91 00:05:16,320 --> 00:05:18,440 And he can see overhead, he can see 92 00:05:18,440 --> 00:05:22,940 where he is with regard to other things in that room. 93 00:05:22,940 --> 00:05:25,100 But remember, that's a whole room. 94 00:05:25,100 --> 00:05:26,970 OK? 95 00:05:26,970 --> 00:05:30,570 Now, Matt is often using a runway 96 00:05:30,570 --> 00:05:33,670 and recording place cells represent 97 00:05:33,670 --> 00:05:35,485 places the rat can be on the runway. 98 00:05:35,485 --> 00:05:38,380 But here, when the rat moves around the room, 99 00:05:38,380 --> 00:05:40,140 you can see that many of these cells 100 00:05:40,140 --> 00:05:42,440 are only active-- when they're very 101 00:05:42,440 --> 00:05:46,600 active he covers the area in red. 102 00:05:46,600 --> 00:05:47,830 OK? 103 00:05:47,830 --> 00:05:51,270 If it's dark blue it means it's not active at all. 104 00:05:51,270 --> 00:05:54,940 So these are place cells. 105 00:05:54,940 --> 00:05:57,030 Cells that are active when the animal 106 00:05:57,030 --> 00:05:58,960 is in one particular place. 107 00:05:58,960 --> 00:06:01,040 That means not where he is looking 108 00:06:01,040 --> 00:06:04,180 but where the animal is located. 109 00:06:04,180 --> 00:06:06,710 That's what a place cell is. 110 00:06:06,710 --> 00:06:10,130 And you can see some of them are very broadly tuned, 111 00:06:10,130 --> 00:06:12,520 some of them are very precisely tuned, 112 00:06:12,520 --> 00:06:16,390 represent a tiny little area. 113 00:06:16,390 --> 00:06:19,580 They tend to find these very dorsally in the hippocampus. 114 00:06:19,580 --> 00:06:22,220 That is at the septal end of the hippocampus, the one 115 00:06:22,220 --> 00:06:24,480 closest to the septum. 116 00:06:24,480 --> 00:06:26,549 And there's some cells that they don't 117 00:06:26,549 --> 00:06:28,340 know what they're doing because they're not 118 00:06:28,340 --> 00:06:29,961 responding to place. 119 00:06:29,961 --> 00:06:30,460 OK? 120 00:06:33,170 --> 00:06:36,480 Some of them may be infected direction cells. 121 00:06:36,480 --> 00:06:36,980 OK. 122 00:06:36,980 --> 00:06:44,450 So when we deal with head direction cells in the system, 123 00:06:44,450 --> 00:06:46,620 this is how we define it. 124 00:06:46,620 --> 00:06:55,520 Here's a rat and here we look at how his body accesses a line. 125 00:06:55,520 --> 00:06:56,600 That's this line. 126 00:07:00,310 --> 00:07:03,830 And the angle here theta is the angle 127 00:07:03,830 --> 00:07:07,120 of the animal from some landmark that the rat 128 00:07:07,120 --> 00:07:10,770 is using to orient himself. 129 00:07:10,770 --> 00:07:12,600 We do the same thing. 130 00:07:12,600 --> 00:07:15,250 Even when you're not aware of the landmark you're using, 131 00:07:15,250 --> 00:07:17,390 we always do this. 132 00:07:17,390 --> 00:07:20,020 So we have a sense of where we are with respect 133 00:07:20,020 --> 00:07:21,270 to things in the environments. 134 00:07:21,270 --> 00:07:23,445 Usually sensed by the visual system. 135 00:07:23,445 --> 00:07:29,920 And there are specific structures in the-- not 136 00:07:29,920 --> 00:07:34,800 in the hippocampus itself, and usually 137 00:07:34,800 --> 00:07:36,630 not in visual cortex itself. 138 00:07:36,630 --> 00:07:40,450 There's not many projections from primary visual cortex 139 00:07:40,450 --> 00:07:43,305 into the system but there are from other areas 140 00:07:43,305 --> 00:07:46,130 that represent landmarks. 141 00:07:48,870 --> 00:07:54,950 So theta is angle-- we call it allocentric direction. 142 00:07:54,950 --> 00:07:56,880 Not the direction where something 143 00:07:56,880 --> 00:07:58,750 is located with respect to the head. 144 00:07:58,750 --> 00:08:00,890 That's egocentric direction. 145 00:08:00,890 --> 00:08:04,350 This is allocentric direction. 146 00:08:04,350 --> 00:08:12,850 And now, if he turns his head by this amount delta theta, 147 00:08:12,850 --> 00:08:16,300 then this allocentric direction can 148 00:08:16,300 --> 00:08:21,000 be corrected if the animal-- now, what's of interest here 149 00:08:21,000 --> 00:08:27,360 is, what places is he headed towards with respect 150 00:08:27,360 --> 00:08:30,460 to the landmark? 151 00:08:30,460 --> 00:08:34,866 So this, then, is the corrected allocentric direction. 152 00:08:34,866 --> 00:08:37,179 It changes all the time depending 153 00:08:37,179 --> 00:08:38,570 on how his head is turned. 154 00:08:40,881 --> 00:08:41,380 OK. 155 00:08:41,380 --> 00:08:43,580 So these are the things you need to know 156 00:08:43,580 --> 00:08:46,610 to understand what's going on. 157 00:08:46,610 --> 00:08:52,700 Now, here's the figure we saw before of the Papez circuit. 158 00:08:52,700 --> 00:08:56,810 Here is the allohippocampal formation, 159 00:08:56,810 --> 00:09:01,040 the part that Papez was familiar with would all be included here 160 00:09:01,040 --> 00:09:06,810 in the dashed line-- hippocampus itself, subiculum next to it, 161 00:09:06,810 --> 00:09:10,510 and then the dentate gyrus at the far end. 162 00:09:13,050 --> 00:09:14,170 OK. 163 00:09:14,170 --> 00:09:19,230 Now, changes in head direction-- and this 164 00:09:19,230 --> 00:09:23,920 we talked about-- they're signaled by vestibular 165 00:09:23,920 --> 00:09:27,830 and probably [? proprioseptum ?] systems in the brain stem. 166 00:09:27,830 --> 00:09:34,800 They come in by way of the-- the so-called tegmental nuclei-- 167 00:09:34,800 --> 00:09:38,580 they're named after-- Gudden named them so they are often 168 00:09:38,580 --> 00:09:42,402 called the tegmental nuclei of Gudden-- 169 00:09:42,402 --> 00:09:43,860 in the column of the brain and they 170 00:09:43,860 --> 00:09:46,590 go through the mammillary bodies. 171 00:09:46,590 --> 00:09:48,870 And in the diagram, that's this pathway. 172 00:09:48,870 --> 00:09:50,970 Here's the tegmental nuclei, here's 173 00:09:50,970 --> 00:09:54,540 the connection to mammillary body. 174 00:09:54,540 --> 00:09:57,230 So what's the mammillary body doing? 175 00:09:57,230 --> 00:09:59,930 Well, the information to the mammillary body 176 00:09:59,930 --> 00:10:04,390 is coming from hippocampus here. 177 00:10:04,390 --> 00:10:10,550 That is constantly giving the mammillary body information 178 00:10:10,550 --> 00:10:11,690 about theta. 179 00:10:15,250 --> 00:10:17,950 So the information from the tegmental nuclei 180 00:10:17,950 --> 00:10:25,630 then is-- changes that activity to theta plus delta theta. 181 00:10:25,630 --> 00:10:30,060 And that's the information on head direction signalled, that 182 00:10:30,060 --> 00:10:34,610 goes up to the cingulate cortex through the anterior 183 00:10:34,610 --> 00:10:35,770 nuclei of the thalamus. 184 00:10:35,770 --> 00:10:37,650 This is the [? mammillary ?] tract. 185 00:10:37,650 --> 00:10:38,150 OK? 186 00:10:46,450 --> 00:10:47,930 So this is just what I said. 187 00:10:51,890 --> 00:10:55,430 The relevance, of course, is that the place-- the animal, 188 00:10:55,430 --> 00:11:03,140 in his internal map, the environment-- 189 00:11:03,140 --> 00:11:06,570 he is anticipating changes in position 190 00:11:06,570 --> 00:11:08,880 by those changes in head direction. 191 00:11:08,880 --> 00:11:11,210 So basically, what I think is happening, 192 00:11:11,210 --> 00:11:13,730 is that every time you turn your head, 193 00:11:13,730 --> 00:11:17,730 or an animal turns its head, you're 194 00:11:17,730 --> 00:11:21,270 aware of the places in that direction. 195 00:11:21,270 --> 00:11:24,770 And those places are associated with memories. 196 00:11:24,770 --> 00:11:29,360 So you're constantly-- that is happening 197 00:11:29,360 --> 00:11:33,050 through these connections, through the hippocampus, 198 00:11:33,050 --> 00:11:35,420 through these paralimbic areas, through the neocortex. 199 00:11:44,230 --> 00:11:48,330 And I point out here that we've only 200 00:11:48,330 --> 00:11:50,660 characterized the head direction cells. 201 00:11:50,660 --> 00:11:56,000 There are other axons in those pathways 202 00:11:56,000 --> 00:11:58,270 that we don't fully understand. 203 00:12:00,900 --> 00:12:03,020 And it also raises the question, what's 204 00:12:03,020 --> 00:12:06,120 the hippocampus sending to other parts of the hypothalamus? 205 00:12:06,120 --> 00:12:08,530 I'd point out here that connections 206 00:12:08,530 --> 00:12:10,690 going to the septal area, to other parts 207 00:12:10,690 --> 00:12:13,400 of the hypothalamus, in addition to this larger 208 00:12:13,400 --> 00:12:15,200 connection to the mammillary body. 209 00:12:15,200 --> 00:12:19,640 So we know the major input to the mammillary bodies concerns 210 00:12:19,640 --> 00:12:22,010 allocentric head direction. 211 00:12:22,010 --> 00:12:22,510 OK? 212 00:12:26,040 --> 00:12:31,090 It may alter motivational states according to the memories being 213 00:12:31,090 --> 00:12:34,350 activated about those potential places. 214 00:12:38,610 --> 00:12:48,540 And let's go back and talk about-- here 215 00:12:48,540 --> 00:12:51,870 we're talking about place memories. 216 00:12:51,870 --> 00:12:58,770 But early on in the book I talked about two major links 217 00:12:58,770 --> 00:13:02,640 between olfactory inputs and motor outputs. 218 00:13:02,640 --> 00:13:04,370 Both of which were classed-- they 219 00:13:04,370 --> 00:13:08,910 represented different kinds of learning. 220 00:13:08,910 --> 00:13:13,110 Two major links between-- this was before the evolution 221 00:13:13,110 --> 00:13:21,220 of visual and other inputs into the endbrain. 222 00:13:21,220 --> 00:13:24,170 So through the ventral endbrain, which 223 00:13:24,170 --> 00:13:30,160 has become the corpus striatum and basal forebrain, 224 00:13:30,160 --> 00:13:31,960 that was one route. 225 00:13:31,960 --> 00:13:36,400 And we know that that's responsible for habits, 226 00:13:36,400 --> 00:13:38,920 and early on they were olfactory habits, 227 00:13:38,920 --> 00:13:43,470 responses to different olfactory cues. 228 00:13:43,470 --> 00:13:46,330 But there were also inputs to the pallium. 229 00:13:46,330 --> 00:13:49,075 The main part of the pallium was the medial pallium 230 00:13:49,075 --> 00:13:51,340 of the dorsal endbrain. 231 00:13:51,340 --> 00:13:52,890 In fact, the rest of it, what we call 232 00:13:52,890 --> 00:13:54,870 dorsal cortex in primitive animals, 233 00:13:54,870 --> 00:13:57,880 is really equivalent to parahippocampal regions 234 00:13:57,880 --> 00:13:58,660 in mammals. 235 00:13:58,660 --> 00:14:03,150 And the major output of those areas is to the medial pallium. 236 00:14:03,150 --> 00:14:07,671 The medial pallium was really the dominant pallial structure 237 00:14:07,671 --> 00:14:08,170 dorsally. 238 00:14:10,960 --> 00:14:15,190 And even in advanced mammalian brains, 239 00:14:15,190 --> 00:14:17,920 if you look at gene expression studies, 240 00:14:17,920 --> 00:14:21,050 there are genes that are expressed 241 00:14:21,050 --> 00:14:24,670 in both the entire neocortex and medial pallium. 242 00:14:29,320 --> 00:14:30,940 And that medial pallium, of course, 243 00:14:30,940 --> 00:14:32,360 became the hippocampal formation. 244 00:14:32,360 --> 00:14:34,530 And we know that that is concerned 245 00:14:34,530 --> 00:14:36,660 with a very different kind of memory. 246 00:14:36,660 --> 00:14:40,210 Not the habits that the stratum is involved with, 247 00:14:40,210 --> 00:14:45,800 but memory for places initially in evolution. 248 00:14:50,390 --> 00:14:52,860 This just takes that same outline 249 00:14:52,860 --> 00:14:55,880 and amplifies it a little bit. 250 00:14:55,880 --> 00:15:01,240 That medial pallium projects through the end 251 00:15:01,240 --> 00:15:02,860 of the ventral striatum, but also 252 00:15:02,860 --> 00:15:07,400 direct to the hypothalamus, also the epithalamus. 253 00:15:07,400 --> 00:15:09,350 Those links were [INAUDIBLE] two of the habits 254 00:15:09,350 --> 00:15:13,660 were different concerning disassociated place 255 00:15:13,660 --> 00:15:18,650 with good or bad consequences approaching those places. 256 00:15:18,650 --> 00:15:24,960 When I talked about these major evolutionary steps, 257 00:15:24,960 --> 00:15:27,790 I mentioned early expansion of the endbrain, 258 00:15:27,790 --> 00:15:30,480 both striatal and pallial. 259 00:15:30,480 --> 00:15:36,000 And I showed two main pathways going caudally 260 00:15:36,000 --> 00:15:38,070 from the olfactory system. 261 00:15:38,070 --> 00:15:41,390 One of them goes to the base of the brain here. 262 00:15:41,390 --> 00:15:43,780 That would be equivalent in modern mammals 263 00:15:43,780 --> 00:15:46,840 to the pathway to the olfactory tubercle which 264 00:15:46,840 --> 00:15:49,680 is the very ventral most part of the ventral striatum. 265 00:15:49,680 --> 00:15:52,010 And the other one goes up to the pallium. 266 00:15:52,010 --> 00:15:56,160 And that would be equivalent to olfactory projections 267 00:15:56,160 --> 00:15:59,060 to hippocampal formation. 268 00:15:59,060 --> 00:16:01,650 They exist even in mammals. 269 00:16:05,320 --> 00:16:09,430 Enhancers, I've traced pathways from the olfactory bulb 270 00:16:09,430 --> 00:16:12,740 to the very anterior most part of the hippocampus. 271 00:16:12,740 --> 00:16:14,690 It's called the hippocampal rudiment. 272 00:16:14,690 --> 00:16:22,280 That actually joins with the septum and the olfactory bulb 273 00:16:22,280 --> 00:16:24,510 projects directly to it. 274 00:16:24,510 --> 00:16:28,230 So you can find remnants of these early pathways. 275 00:16:28,230 --> 00:16:31,590 We already talked about olfactory projections 276 00:16:31,590 --> 00:16:35,470 and I talked about how the olfactory bulb dominated 277 00:16:35,470 --> 00:16:43,080 the whole pallium in the-- say, in hagfish and the sea lamprey. 278 00:16:43,080 --> 00:16:43,830 All right. 279 00:16:43,830 --> 00:16:46,530 Let's look at that medial pallium in these animals. 280 00:16:46,530 --> 00:16:50,070 The shark, the lungfish, the bullfrog and marsupial. 281 00:16:50,070 --> 00:16:51,070 There's only one mammal. 282 00:16:51,070 --> 00:16:52,860 I picked the marsupial here because he 283 00:16:52,860 --> 00:16:54,580 doesn't have a corpus callosum so he's 284 00:16:54,580 --> 00:16:58,310 most similar to these other animals in the way 285 00:16:58,310 --> 00:17:00,510 the cortex is arranged. 286 00:17:00,510 --> 00:17:01,010 OK? 287 00:17:03,900 --> 00:17:07,680 And just look at the major change 288 00:17:07,680 --> 00:17:10,849 in the configuration of the medial pallium. 289 00:17:10,849 --> 00:17:14,440 In those animals-- the shark, lungfish and bullfrog-- 290 00:17:14,440 --> 00:17:16,560 we call the more primitive vertebrates, 291 00:17:16,560 --> 00:17:18,210 and then the hippocampus in mammals. 292 00:17:21,140 --> 00:17:24,210 We could say birds as well, but things 293 00:17:24,210 --> 00:17:26,269 have evolved quite differently in the endbrians, 294 00:17:26,269 --> 00:17:30,220 as you know, in birds so I'll be focusing on mammals more. 295 00:17:30,220 --> 00:17:31,350 But here it is. 296 00:17:31,350 --> 00:17:39,700 I've colored it in pink from the studies that I was using. 297 00:17:39,700 --> 00:17:45,630 And here you see the dominance in size of the medial pallium 298 00:17:45,630 --> 00:17:47,840 compared with the rest of the dorsal cortex. 299 00:17:47,840 --> 00:17:49,920 This is olfactory cortex down here. 300 00:17:52,520 --> 00:17:55,790 That's lateral pallium. 301 00:17:55,790 --> 00:17:58,620 That's olfactory cortex. 302 00:17:58,620 --> 00:18:01,490 This is a striatal structure here 303 00:18:01,490 --> 00:18:04,040 and this is the septal area. 304 00:18:04,040 --> 00:18:06,420 So there's the medial pallium of a shark. 305 00:18:06,420 --> 00:18:07,470 It's a spiny dogfish. 306 00:18:07,470 --> 00:18:10,490 It's a very small shark. 307 00:18:10,490 --> 00:18:14,260 And here in an African lungfish, again, 308 00:18:14,260 --> 00:18:16,280 if you look at the-- well this is actually 309 00:18:16,280 --> 00:18:19,382 olfactory bulb here-- but if you look at this level 310 00:18:19,382 --> 00:18:22,740 when you're behind the olfactory bulb, 311 00:18:22,740 --> 00:18:26,020 here you have the dorsal pallium. 312 00:18:26,020 --> 00:18:29,315 This is olfactory cortex, the lateral pallium, 313 00:18:29,315 --> 00:18:31,960 this is striatal. 314 00:18:31,960 --> 00:18:33,780 And there's the medial pallium. 315 00:18:33,780 --> 00:18:34,870 You'll see it here. 316 00:18:34,870 --> 00:18:38,520 It's thicker, it's more differentiated than the rest. 317 00:18:38,520 --> 00:18:41,000 And here's a bullfrog. 318 00:18:41,000 --> 00:18:45,230 It's even more striking how thick the medial pallium 319 00:18:45,230 --> 00:18:51,870 is here compared to the rest of the non olfactory pallium. 320 00:18:51,870 --> 00:18:54,310 And by the way, on the bullfrog, that medial pallium 321 00:18:54,310 --> 00:18:58,640 does get some direct olfactory inputs. 322 00:18:58,640 --> 00:19:00,170 But much of it does not. 323 00:19:03,060 --> 00:19:05,470 The same is true of this dorsal cortex. 324 00:19:05,470 --> 00:19:08,440 It gets a little olfactory input directly out here. 325 00:19:12,890 --> 00:19:15,580 Now, here is the Virginia opossum. 326 00:19:15,580 --> 00:19:17,120 So now we're talking about mammals, 327 00:19:17,120 --> 00:19:24,010 a mammal without any corpus callosum You would think he's 328 00:19:24,010 --> 00:19:28,380 a natural split brain animal, but in fact he isn't at all. 329 00:19:28,380 --> 00:19:30,800 Just the fact that he doesn't have a corpus callosum 330 00:19:30,800 --> 00:19:33,430 doesn't mean a whole lot because the axons still 331 00:19:33,430 --> 00:19:35,080 go from one hemisphere to another. 332 00:19:35,080 --> 00:19:36,896 How do they get there? 333 00:19:36,896 --> 00:19:38,650 Do any of you know? 334 00:19:43,382 --> 00:19:47,430 If you're looking at, say, areas next 335 00:19:47,430 --> 00:19:52,360 to the primary visual areas, and even the striate cortex 336 00:19:52,360 --> 00:19:55,060 has some axons that go across the callosum, the ones 337 00:19:55,060 --> 00:19:58,290 representing the vertical meridian. 338 00:19:58,290 --> 00:20:00,290 But how do they get there in the opossum? 339 00:20:00,290 --> 00:20:03,260 How do they cross to the other side? 340 00:20:03,260 --> 00:20:07,694 They go all the way forward into the anterior commissure, 341 00:20:07,694 --> 00:20:09,235 the structure in the basal forebrain. 342 00:20:12,220 --> 00:20:15,310 Ventral to most of the septal area. 343 00:20:15,310 --> 00:20:17,770 That's where they cross. 344 00:20:17,770 --> 00:20:22,540 So the anterior commissure is huge. 345 00:20:22,540 --> 00:20:27,110 All of these areas, this is all commissure axons here. 346 00:20:27,110 --> 00:20:27,840 It's so huge. 347 00:20:27,840 --> 00:20:32,050 It's not that big in any of the non mammalian-- 348 00:20:32,050 --> 00:20:37,990 in any of the mammalian animals except the various marsupials. 349 00:20:42,890 --> 00:20:46,030 So here's the neocortex up here. 350 00:20:46,030 --> 00:20:49,890 You follow it around through a cortical area 351 00:20:49,890 --> 00:20:53,210 with fewer layers, the cingulate cortex. 352 00:20:53,210 --> 00:20:55,650 It's also got that very prominent layer two. 353 00:20:58,700 --> 00:21:01,320 And then, right here, you're suddenly 354 00:21:01,320 --> 00:21:03,420 through some transitional areas here. 355 00:21:03,420 --> 00:21:05,881 You're in hippocampal formation. 356 00:21:05,881 --> 00:21:07,755 And if you've followed the hippocampus around 357 00:21:07,755 --> 00:21:12,030 and cross-sectioned you come to the dentate gyrus. 358 00:21:12,030 --> 00:21:19,190 And the dentate gyrus, here at this level, abuts the septum. 359 00:21:19,190 --> 00:21:20,530 This is the septal area. 360 00:21:23,350 --> 00:21:25,770 The only way you see that in the labs 361 00:21:25,770 --> 00:21:29,250 we-- the animals we study in the lab, the mouse and the rat 362 00:21:29,250 --> 00:21:33,400 primarily, is to look at the hippocampal rudiment which 363 00:21:33,400 --> 00:21:36,229 you find just above the corpus callosum. 364 00:21:36,229 --> 00:21:37,770 But around the front of the callosum, 365 00:21:37,770 --> 00:21:40,645 you'll see that structure coming down and joining 366 00:21:40,645 --> 00:21:43,580 with the septum the same way. 367 00:21:43,580 --> 00:21:46,830 This is much clearer in the marsupial 368 00:21:46,830 --> 00:21:50,410 where we can see it much further anteriorly also. 369 00:21:50,410 --> 00:21:54,390 The hippocampus does get a lot bigger in this animal people 370 00:21:54,390 --> 00:21:55,650 if you go caudally. 371 00:21:55,650 --> 00:21:59,796 Because it's become much larger posteriorly 372 00:21:59,796 --> 00:22:01,170 where it's neat the visual areas. 373 00:22:04,870 --> 00:22:08,480 I already pointed out how important visual landmarks 374 00:22:08,480 --> 00:22:12,390 are to the function of that major function 375 00:22:12,390 --> 00:22:17,570 of the hippocampal formation in responding differently 376 00:22:17,570 --> 00:22:20,610 in different places. 377 00:22:20,610 --> 00:22:22,360 The importance of visual information 378 00:22:22,360 --> 00:22:26,130 has led to most of the expansion of the hippocampus 379 00:22:26,130 --> 00:22:29,260 next to the visual areas. 380 00:22:29,260 --> 00:22:33,470 So here it is in a rat where you see the-- here 381 00:22:33,470 --> 00:22:36,200 they cut out cortex in this drawing 382 00:22:36,200 --> 00:22:38,321 to show the hippocampus underneath. 383 00:22:38,321 --> 00:22:39,820 And they're showing that if you make 384 00:22:39,820 --> 00:22:44,840 a cut across the longitudinal axis of the hippocampus-- 385 00:22:44,840 --> 00:22:46,820 you see there-- you'll always get 386 00:22:46,820 --> 00:22:50,331 a slice that contains the same circuit. 387 00:22:50,331 --> 00:22:52,080 And we're going to go through that circuit 388 00:22:52,080 --> 00:22:54,380 in more detail in a minute. 389 00:22:54,380 --> 00:22:56,250 So if you look at it dorsally, if you 390 00:22:56,250 --> 00:22:58,080 want to get at the hippocampus, you 391 00:22:58,080 --> 00:23:02,414 have to cut a window through the cortex-- through the neocortex, 392 00:23:02,414 --> 00:23:05,120 and you expose the hippocampus underneath. 393 00:23:05,120 --> 00:23:09,640 You don't just go through and exposed cells. 394 00:23:09,640 --> 00:23:12,180 You have to go through the cortex. 395 00:23:12,180 --> 00:23:13,740 And this is just a drawing of that. 396 00:23:13,740 --> 00:23:15,290 They've blown it up. 397 00:23:15,290 --> 00:23:15,790 OK. 398 00:23:15,790 --> 00:23:19,750 And here, this is a reconstruction of the hamster 399 00:23:19,750 --> 00:23:20,420 that I did. 400 00:23:20,420 --> 00:23:23,890 And here you see a dorsal view of the hemisphere. 401 00:23:23,890 --> 00:23:26,610 And there's where the hippocampus is. 402 00:23:26,610 --> 00:23:29,190 And then in orange I showed the axons 403 00:23:29,190 --> 00:23:32,560 coming from hippocampus going into the fornix. 404 00:23:32,560 --> 00:23:35,630 This is the columns of the fornix where they then 405 00:23:35,630 --> 00:23:39,120 come down, go through the caudal end of the septal area 406 00:23:39,120 --> 00:23:41,910 on their way to the mammillary bodies in the hypothalamus. 407 00:23:41,910 --> 00:23:45,659 And they also show axons crossing from one hippocampus 408 00:23:45,659 --> 00:23:46,200 to the other. 409 00:23:46,200 --> 00:23:48,090 The hippocampal commissure. 410 00:23:48,090 --> 00:23:50,110 So here in the side view, there's 411 00:23:50,110 --> 00:23:54,190 the fat cigar of the hippocampus. 412 00:23:54,190 --> 00:23:56,720 Of fat banana, if you will. 413 00:23:56,720 --> 00:24:00,140 Ventral hippocampus, dorsal hippocampus, 414 00:24:00,140 --> 00:24:04,020 here are the fornix fibers coming out of the hippocampus, 415 00:24:04,020 --> 00:24:08,490 mostly from the subiculum, which we'll 416 00:24:08,490 --> 00:24:11,480 see the way it looks in the cell stain. 417 00:24:11,480 --> 00:24:14,780 It's really part of the hippocampus. 418 00:24:14,780 --> 00:24:17,340 And then there's the bend. 419 00:24:17,340 --> 00:24:21,860 This is going around the internal capsule. 420 00:24:21,860 --> 00:24:24,770 The internal capsule fibers that connect thalamus to the cortex 421 00:24:24,770 --> 00:24:26,590 are coming through here. 422 00:24:26,590 --> 00:24:31,055 There it goes-- it's forming this column, compact column, 423 00:24:31,055 --> 00:24:33,270 of fibers that you can follow all 424 00:24:33,270 --> 00:24:34,900 the way to the mammillary bodies there 425 00:24:34,900 --> 00:24:37,570 at the caudal end of the hypothalamus. 426 00:24:37,570 --> 00:24:39,600 So this, of course, is underneath. 427 00:24:39,600 --> 00:24:45,870 This is, in the hemisphere, this is in the branch down here. 428 00:24:45,870 --> 00:24:51,420 And this just shows you someone's imagination more 429 00:24:51,420 --> 00:24:54,838 than an actual reconstruction of where that is in the rat brain. 430 00:24:59,780 --> 00:25:06,050 And here they call this the-- this is the temporal end. 431 00:25:06,050 --> 00:25:08,100 You could call it the amygdalar end 432 00:25:08,100 --> 00:25:11,190 because it's the amygdala sits right there. 433 00:25:11,190 --> 00:25:11,840 OK? 434 00:25:11,840 --> 00:25:16,380 That's here and this is the temporal end in the hamster. 435 00:25:16,380 --> 00:25:19,730 And this is, they call it the septal end. 436 00:25:19,730 --> 00:25:22,186 Closest to the septum. 437 00:25:22,186 --> 00:25:25,190 Because the septum, you see, is right there. 438 00:25:25,190 --> 00:25:28,590 This is all septum. 439 00:25:28,590 --> 00:25:30,270 There's the septal area here. 440 00:25:30,270 --> 00:25:33,960 And I show some of the axons that 441 00:25:33,960 --> 00:25:36,870 are leaving the rest of the-- we call this 442 00:25:36,870 --> 00:25:39,990 the precommissural fornix, the axons 443 00:25:39,990 --> 00:25:45,590 that leave the main bundle of the fornix columns 444 00:25:45,590 --> 00:25:48,540 and connect mainly with the septal area 445 00:25:48,540 --> 00:25:52,990 and other structures in the basal forebrain region. 446 00:25:56,170 --> 00:25:59,380 So now we want to identify the major sub 447 00:25:59,380 --> 00:26:04,470 regions of the hippocampus and the adjacent structures, 448 00:26:04,470 --> 00:26:07,076 and look at the pattern of interconnectivity 449 00:26:07,076 --> 00:26:10,035 that everybody in the [INAUDIBLE] lab 450 00:26:10,035 --> 00:26:13,220 knows about because they study it 451 00:26:13,220 --> 00:26:16,990 and they look at changes in the various synapses. 452 00:26:16,990 --> 00:26:22,850 And these different regions, which you see here, 453 00:26:22,850 --> 00:26:31,970 are labeled CA1, CA2, CA3, and these loosely packed cells 454 00:26:31,970 --> 00:26:33,400 here, CA4. 455 00:26:33,400 --> 00:26:35,840 And then dentate gyrus. 456 00:26:35,840 --> 00:26:40,510 Whenever you cut-- this is a horizontal section of a rat, 457 00:26:40,510 --> 00:26:42,630 and wherever you cut if you're cutting 458 00:26:42,630 --> 00:26:52,200 across the long axis-- meaning this way, this way, this way-- 459 00:26:52,200 --> 00:26:56,970 as long as you cut that way across the long axis, 460 00:26:56,970 --> 00:27:02,370 you're going to get sections that have this appearance. 461 00:27:02,370 --> 00:27:03,050 OK? 462 00:27:03,050 --> 00:27:07,890 So you see the same basic circuit at all these levels. 463 00:27:07,890 --> 00:27:09,510 And we'll follow that circuit. 464 00:27:09,510 --> 00:27:13,910 But first, what does CA mean? 465 00:27:13,910 --> 00:27:19,170 Cornu Ammonis, the horn of Amon. 466 00:27:19,170 --> 00:27:20,940 Amon was a Greek god. 467 00:27:20,940 --> 00:27:25,840 I'm sorry, Egyptian god, sun god. 468 00:27:25,840 --> 00:27:30,060 And he carried a horn. 469 00:27:30,060 --> 00:27:32,700 So these names come from mythology. 470 00:27:32,700 --> 00:27:34,710 In this case, Egyptian mythology. 471 00:27:38,050 --> 00:27:40,650 So it means the horn of Amon. 472 00:27:40,650 --> 00:27:42,860 Nowadays, students who do research on it 473 00:27:42,860 --> 00:27:46,380 sometimes don't even know who Amon was. 474 00:27:46,380 --> 00:27:49,780 Unless they read my book. 475 00:27:49,780 --> 00:27:54,010 They certainly know CA1, 2, 3 and 4 are, 476 00:27:54,010 --> 00:27:56,860 and what the dentate gyrus is. 477 00:27:56,860 --> 00:28:01,890 But notice, if you start here at the dentate gyrus end, 478 00:28:01,890 --> 00:28:07,270 you go CA4 down to CA1 which ends right here. 479 00:28:07,270 --> 00:28:10,570 And then the configuration itself changes. 480 00:28:10,570 --> 00:28:12,850 This is called the subiculum, where 481 00:28:12,850 --> 00:28:17,630 the cells have this broader layer. 482 00:28:17,630 --> 00:28:20,240 It's really part of the hippocampus, 483 00:28:20,240 --> 00:28:22,140 but it's where the cells are broader. 484 00:28:22,140 --> 00:28:25,700 Well, most of the output into the fornix going 485 00:28:25,700 --> 00:28:28,850 to the mammillary bodies is actually coming from this area, 486 00:28:28,850 --> 00:28:29,750 from the subiculum. 487 00:28:35,020 --> 00:28:39,679 And if you keep going, now you get additional layers. 488 00:28:39,679 --> 00:28:40,720 This is the presubiculum. 489 00:28:43,970 --> 00:28:45,140 This cortex. 490 00:28:45,140 --> 00:28:48,800 And then you get-- and they do name sometimes 491 00:28:48,800 --> 00:28:52,940 additional areas like parasubiculum, prosubiculum, 492 00:28:52,940 --> 00:28:54,290 you don't need to know all that. 493 00:28:54,290 --> 00:29:01,760 Subiculum, presubiculum, then you get to the entorhinal area. 494 00:29:01,760 --> 00:29:04,880 Entorhinal area is well known to physiologists 495 00:29:04,880 --> 00:29:06,790 who studied the system because it 496 00:29:06,790 --> 00:29:21,840 is the major bridge between neocortex-- association 497 00:29:21,840 --> 00:29:22,740 areas of neocortex. 498 00:29:25,690 --> 00:29:28,820 The major paralimbic area here is entorhinal. 499 00:29:31,600 --> 00:29:34,460 And that's the major route, especially 500 00:29:34,460 --> 00:29:36,012 this one through the dentate gyrus. 501 00:29:36,012 --> 00:29:37,970 But it also connects directly to the subiculum. 502 00:29:53,940 --> 00:29:57,240 So if you look at question three here, I'm asking what's 503 00:29:57,240 --> 00:30:00,310 the name of the major afferent input 504 00:30:00,310 --> 00:30:02,900 pathway to the mammalian hippocampus? 505 00:30:02,900 --> 00:30:04,560 Where does it originate? 506 00:30:04,560 --> 00:30:07,310 That would be the pathway you should describe. 507 00:30:07,310 --> 00:30:08,860 OK? 508 00:30:08,860 --> 00:30:18,380 The one from entorhinal area that goes through this way 509 00:30:18,380 --> 00:30:19,950 into the dentate gyrus. 510 00:30:19,950 --> 00:30:29,870 It actually seems to pene-- this is actually a deep sulcus. 511 00:30:29,870 --> 00:30:32,130 But in evolution, axons have actually 512 00:30:32,130 --> 00:30:34,430 crossed directly there. 513 00:30:34,430 --> 00:30:37,380 So we call it the perforant path because it perforates 514 00:30:37,380 --> 00:30:42,080 what is actually peeled surface of the brain. 515 00:30:47,260 --> 00:30:48,790 Let's look at that circuit. 516 00:30:48,790 --> 00:30:52,170 But before then, what's the difference 517 00:30:52,170 --> 00:30:54,500 in location of the hippocampus in large primates 518 00:30:54,500 --> 00:30:56,458 and it's location and it's location in the rat? 519 00:30:56,458 --> 00:30:58,265 Because I've been stressing here the rat. 520 00:31:01,230 --> 00:31:07,590 If you look at human, they've shown the hippocampus 521 00:31:07,590 --> 00:31:13,940 in red here-- the temporal end and this would 522 00:31:13,940 --> 00:31:16,580 be the septal end-- and notice that now, what 523 00:31:16,580 --> 00:31:21,340 is ventral in the rat is really anterior 524 00:31:21,340 --> 00:31:23,200 in the human because of this shift 525 00:31:23,200 --> 00:31:28,435 into the temporal lobe of the primarily visual areas. 526 00:31:28,435 --> 00:31:30,390 Now, there's auditory cortex here too, 527 00:31:30,390 --> 00:31:33,560 but this is all visual cortex. 528 00:31:33,560 --> 00:31:37,720 It's the striated area here and then 529 00:31:37,720 --> 00:31:43,540 the areas next to striated-- B2, B3, B4-- and then you 530 00:31:43,540 --> 00:31:46,550 get into infratemporal areas all along here. 531 00:31:46,550 --> 00:31:47,810 This is all visual. 532 00:31:51,470 --> 00:31:55,810 The hippocampus can be followed all the way down here. 533 00:31:55,810 --> 00:32:02,550 This equivalent to the ventral hippocampus, the anterior 534 00:32:02,550 --> 00:32:05,700 hippocampus in the primates, large primates, 535 00:32:05,700 --> 00:32:09,850 was the part nearest the amygdala there. 536 00:32:09,850 --> 00:32:13,110 And this is where the place cells are quite large. 537 00:32:13,110 --> 00:32:16,100 This is equivalent to more dorsal hippocampus. 538 00:32:16,100 --> 00:32:18,740 They show it as, I think, it's probably a little too narrow 539 00:32:18,740 --> 00:32:22,550 there because it's actually pretty substantial in humans. 540 00:32:22,550 --> 00:32:25,680 So that's where you get the smaller place cells. 541 00:32:25,680 --> 00:32:29,180 And I said, what's the hippocampal rudiment? 542 00:32:29,180 --> 00:32:32,760 Here I've redone-- it's just to emphasize a little bit 543 00:32:32,760 --> 00:32:37,140 the hippocampal rudiment-- this is hippocampus continually 544 00:32:37,140 --> 00:32:38,860 all the way. 545 00:32:38,860 --> 00:32:41,570 At the very-- right above the [? callus, ?] 546 00:32:41,570 --> 00:32:43,670 all the way here to the septal nuclei, 547 00:32:43,670 --> 00:32:46,140 you can follow hippocampus. 548 00:32:46,140 --> 00:32:50,310 So you see the hippocampus is the medial pallium everywhere. 549 00:32:52,870 --> 00:32:56,592 For the entire-- everywhere in neocortex, 550 00:32:56,592 --> 00:33:00,410 if you follow it medially, you come to hippocampus. 551 00:33:00,410 --> 00:33:05,290 It's just that it's very small except when you're 552 00:33:05,290 --> 00:33:07,501 near the visual areas caudally. 553 00:33:07,501 --> 00:33:08,000 OK? 554 00:33:19,420 --> 00:33:23,500 So we've answered number six here. 555 00:33:23,500 --> 00:33:25,750 And now I want to describe that circuit that 556 00:33:25,750 --> 00:33:28,700 begins in the entorhinal cortex and can be followed 557 00:33:28,700 --> 00:33:32,570 through the hippocampus to the subiculum. 558 00:33:32,570 --> 00:33:35,750 And from there, as I mentioned, the major output 559 00:33:35,750 --> 00:33:39,355 to the mammillary bodies starts. 560 00:33:43,090 --> 00:33:48,420 And then we want to answer this, where can physiologists 561 00:33:48,420 --> 00:33:50,750 get the changes in the synapse that we call on 562 00:33:50,750 --> 00:33:51,750 from potentiation? 563 00:33:51,750 --> 00:33:55,090 Just by rapidly simulating the pathway. 564 00:33:55,090 --> 00:33:59,070 Actually, they get it at every synapse through this pathway. 565 00:33:59,070 --> 00:34:05,070 So here I've taken a picture drawn from Golgi material 566 00:34:05,070 --> 00:34:09,639 by Ramon y Cajal, and I'm picturing that pathway 567 00:34:09,639 --> 00:34:15,440 because I've colored in axons that he had numbered 568 00:34:15,440 --> 00:34:21,550 but he hadn't colored them, beginning 569 00:34:21,550 --> 00:34:25,500 with axon coming out of the white matter here. 570 00:34:25,500 --> 00:34:29,049 It's actually originated in the entorhinal cortex which 571 00:34:29,049 --> 00:34:33,150 is out here off to the right. 572 00:34:33,150 --> 00:34:35,350 So this is the first axon in the pathway 573 00:34:35,350 --> 00:34:40,790 coming from entorhinal cortex, here's this perforant pathway 574 00:34:40,790 --> 00:34:44,870 coming directly into the dentate gyrus 575 00:34:44,870 --> 00:34:50,199 where the axons then travel parallel to the surface 576 00:34:50,199 --> 00:34:52,989 after they enter and terminate on dendrites 577 00:34:52,989 --> 00:34:55,900 of the dentate gyrus. 578 00:34:55,900 --> 00:35:02,660 Then I show a dentate gyrus cell here that's getting that input. 579 00:35:02,660 --> 00:35:07,240 And I'm showing it for this one. 580 00:35:07,240 --> 00:35:09,920 So here the input's coming into the dendrites, 581 00:35:09,920 --> 00:35:15,970 here's the axon of the dentate gyrus cell that you can follow, 582 00:35:15,970 --> 00:35:21,290 travels through the dendritic layer of the hippocampus, 583 00:35:21,290 --> 00:35:27,558 and it synapses on the CA3 neurons. 584 00:35:27,558 --> 00:35:28,930 This is CA3. 585 00:35:28,930 --> 00:35:32,867 CA4 is in this region, they hilus of the dentate gyrus. 586 00:35:32,867 --> 00:35:34,200 That's not where they terminate. 587 00:35:34,200 --> 00:35:39,370 They terminate on CA3 primarily. 588 00:35:39,370 --> 00:35:45,600 And then, the cells in CA3 project-- through axon number 589 00:35:45,600 --> 00:35:50,200 three-- they project to cells in CA1. 590 00:35:50,200 --> 00:35:51,020 This cell here. 591 00:35:53,580 --> 00:35:57,130 And notice that that axon has a branch that 592 00:35:57,130 --> 00:36:00,010 goes right into the fornix. 593 00:36:00,010 --> 00:36:03,490 So areas other than the subiculum here 594 00:36:03,490 --> 00:36:08,430 do project into the fornix, including the CA3 cells. 595 00:36:08,430 --> 00:36:10,430 So then here is-- so this would be 596 00:36:10,430 --> 00:36:17,460 the third axon in that pathway through the hippocampus 597 00:36:17,460 --> 00:36:24,390 and the CA3 cell to a CA1 cell which I show here. 598 00:36:24,390 --> 00:36:27,750 I'm not saying that it doesn't terminate on other cells 599 00:36:27,750 --> 00:36:28,740 here too. 600 00:36:28,740 --> 00:36:32,090 I'm showing one of them here to show an axon. 601 00:36:32,090 --> 00:36:35,140 And Cajal simply drew the output going 602 00:36:35,140 --> 00:36:38,910 into the fimbria of the fornix. 603 00:36:38,910 --> 00:36:42,400 In other words, through axons through the fornix. 604 00:36:42,400 --> 00:36:47,390 But now we know that it also connects-- 605 00:36:47,390 --> 00:36:51,540 I drew it in purple because it wasn't in Cajal's original-- it 606 00:36:51,540 --> 00:36:56,520 goes through a subiculum cell which then has an axon going 607 00:36:56,520 --> 00:36:57,990 into the fimbria. 608 00:36:57,990 --> 00:37:03,090 And in fact, these cells provide the majority of those output 609 00:37:03,090 --> 00:37:06,730 axons that go to the mammillary bodies. 610 00:37:06,730 --> 00:37:08,870 But you see it's fairly complex, even 611 00:37:08,870 --> 00:37:13,970 in these simple Golgi drawings. 612 00:37:13,970 --> 00:37:18,130 And I had to draw this one in because it didn't stain 613 00:37:18,130 --> 00:37:20,410 as well in the Golgi stain that Cajal 614 00:37:20,410 --> 00:37:25,790 was using so he didn't see that pathway. 615 00:37:25,790 --> 00:37:26,330 All right. 616 00:37:32,970 --> 00:37:37,850 Remember, I said that if you cut across the long axis, 617 00:37:37,850 --> 00:37:40,705 as you see there, you always see that pathway. 618 00:37:40,705 --> 00:37:42,280 And here they've drawn it again. 619 00:37:44,920 --> 00:37:48,940 Some of these drawings that you see in textbooks, they 620 00:37:48,940 --> 00:37:53,350 show these axons go directly in. 621 00:37:53,350 --> 00:37:56,870 Like they show this one going into the fornix. 622 00:37:56,870 --> 00:37:59,540 They show this one, similarly. 623 00:37:59,540 --> 00:38:03,590 But now we know even more of them come from the subiculum. 624 00:38:03,590 --> 00:38:06,800 And this is known from experimental work. 625 00:38:06,800 --> 00:38:11,450 You sometimes miss some major things when you just use Golgi. 626 00:38:11,450 --> 00:38:14,205 You need to do experiments with labeled pathways 627 00:38:14,205 --> 00:38:16,250 and trace them. 628 00:38:16,250 --> 00:38:18,120 The imaging methods, too, live imaging 629 00:38:18,120 --> 00:38:19,970 would miss all that too. 630 00:38:19,970 --> 00:38:23,840 So we know this from experimental tracing studies. 631 00:38:23,840 --> 00:38:25,650 So you can characterize the pathway, 632 00:38:25,650 --> 00:38:28,180 as I've shown at the bottom here. 633 00:38:28,180 --> 00:38:31,760 The dentate gyrus cells with their dendrites getting input 634 00:38:31,760 --> 00:38:38,120 from different parts of the-- through the perforant pathway, 635 00:38:38,120 --> 00:38:40,610 different parts of the entorhinal cortex. 636 00:38:40,610 --> 00:38:43,440 This is the lateral perforant pathway, the medial perforant 637 00:38:43,440 --> 00:38:48,100 pathway coming from different parts of the lateral and medial 638 00:38:48,100 --> 00:38:49,940 parts of the [? inferential ?] cortex. 639 00:38:49,940 --> 00:38:55,420 They project then to dendrites in the CA3 region. 640 00:38:55,420 --> 00:38:58,130 And then this collateral, anyway, the Schaffer 641 00:38:58,130 --> 00:39:00,150 collateral. 642 00:39:00,150 --> 00:39:02,020 Named after, of course, a guy named 643 00:39:02,020 --> 00:39:06,430 Schaffer and his projecting to dendrites to CA1 644 00:39:06,430 --> 00:39:10,230 which then projects to subiculum cells as you see here. 645 00:39:10,230 --> 00:39:14,600 And that shows an output and angular bundle 646 00:39:14,600 --> 00:39:23,530 going into the fornix and on to the mammillary bodies. 647 00:39:23,530 --> 00:39:26,570 And I point out here that long-term potentiation 648 00:39:26,570 --> 00:39:30,680 can encourage at each of those synapses. 649 00:39:30,680 --> 00:39:35,516 This synapse, this synapse, this synapse, and this synapse. 650 00:39:35,516 --> 00:39:40,030 They've studied each connection separately 651 00:39:40,030 --> 00:39:44,180 in places like the Tonegawa Lab. 652 00:39:44,180 --> 00:39:47,470 They tend to focus on certain ones in their findings 653 00:39:47,470 --> 00:39:52,820 and their different functions and different components 654 00:39:52,820 --> 00:39:54,320 of the hippocampus. 655 00:39:54,320 --> 00:39:56,310 But a lot of that is still up in the air. 656 00:40:03,200 --> 00:40:07,260 So we know about LTP, but if you think more broadly in terms 657 00:40:07,260 --> 00:40:11,940 of function, what we call behavioral studies call 658 00:40:11,940 --> 00:40:17,470 our memories, what kind of memory are we talking about? 659 00:40:17,470 --> 00:40:21,160 It's not the kind of habit memories 660 00:40:21,160 --> 00:40:24,264 that we talked about in striatum. 661 00:40:24,264 --> 00:40:27,250 AUDIENCE: [INAUDIBLE]? 662 00:40:27,250 --> 00:40:31,850 PROFESSOR: When we talk about long-term memory, yes. 663 00:40:31,850 --> 00:40:34,040 How is that different from-- I mean, 664 00:40:34,040 --> 00:40:37,840 I have a long-term memories learning 665 00:40:37,840 --> 00:40:39,830 how to manipulate a pencil too. 666 00:40:39,830 --> 00:40:41,367 Isn't that a long-term memory? 667 00:40:41,367 --> 00:40:42,200 Is that hippocampal? 668 00:40:44,985 --> 00:40:48,948 AUDIENCE: It's not something like going out [INAUDIBLE]? 669 00:40:52,300 --> 00:40:53,460 PROFESSOR: What kind? 670 00:40:53,460 --> 00:40:55,460 AUDIENCE: [INAUDIBLE] memory. 671 00:40:55,460 --> 00:40:58,940 PROFESSOR: It's a striatal memory. 672 00:40:58,940 --> 00:41:03,290 In terms of the anatomy, that's a striatal memory. 673 00:41:03,290 --> 00:41:06,450 Learning how to ride a bike, learning a sport, these actions 674 00:41:06,450 --> 00:41:10,540 where you don't remember a specific time and place, 675 00:41:10,540 --> 00:41:14,050 you remember a movement. 676 00:41:14,050 --> 00:41:17,850 So whenever you're learning any movement. 677 00:41:17,850 --> 00:41:20,745 I'm not saying that right at the beginning 678 00:41:20,745 --> 00:41:23,700 there aren't multiple types of memory involved. 679 00:41:23,700 --> 00:41:25,930 But someone with hippocampal lesions, 680 00:41:25,930 --> 00:41:30,910 someone like Henry M. who had major hippocampal damage, 681 00:41:30,910 --> 00:41:33,740 he couldn't perform normal long-term memories 682 00:41:33,740 --> 00:41:37,750 but you could teach him sensory motor habits. 683 00:41:37,750 --> 00:41:39,420 OK? 684 00:41:39,420 --> 00:41:41,140 Simply reward him repeatedly. 685 00:41:41,140 --> 00:41:44,080 He wouldn't remember being in the learning situation, 686 00:41:44,080 --> 00:41:47,410 he wouldn't remember the teacher, 687 00:41:47,410 --> 00:41:49,955 but he would gain those skills. 688 00:41:52,790 --> 00:41:54,375 That's one of the types of research 689 00:41:54,375 --> 00:41:57,250 that's clearly separated these two kinds of memory. 690 00:41:59,872 --> 00:42:02,150 And it's the striatum that's the main brain 691 00:42:02,150 --> 00:42:07,800 areas that that happens. 692 00:42:07,800 --> 00:42:13,150 Now, there's a pathway where the sub-cortical projections 693 00:42:13,150 --> 00:42:17,333 go to and from the hippocampus that is not hypothalamus. 694 00:42:20,446 --> 00:42:22,446 And it uses acetylcholine as a neurotransmitter. 695 00:42:24,960 --> 00:42:27,230 It's a neuromodulator-- a major neuromodulator 696 00:42:27,230 --> 00:42:30,260 in the hippocampus. 697 00:42:30,260 --> 00:42:35,740 It's this pathway from the septal area here back 698 00:42:35,740 --> 00:42:37,090 to the hippocampus. 699 00:42:37,090 --> 00:42:43,500 And I show that-- I show pathways 700 00:42:43,500 --> 00:42:46,780 going from the hippocampal formation to septum 701 00:42:46,780 --> 00:42:50,435 and I show this acetylcholine pathway going from septalary 702 00:42:50,435 --> 00:42:51,550 to hippocampus. 703 00:42:51,550 --> 00:42:54,620 That's the answer to this question. 704 00:42:54,620 --> 00:42:56,860 And this is from on human. 705 00:42:56,860 --> 00:42:59,940 And I know these human things are a little more confusing 706 00:42:59,940 --> 00:43:02,125 but this is what you get in medical schools text 707 00:43:02,125 --> 00:43:03,450 so I show them once in a while. 708 00:43:03,450 --> 00:43:06,350 This is the septal area shown here, 709 00:43:06,350 --> 00:43:09,660 this is the arch-- the arch of fornication, remember? 710 00:43:09,660 --> 00:43:13,590 The fornix-- arch of the fornix fibers. 711 00:43:13,590 --> 00:43:18,115 And there, in purple, I've drawn acetylcholine axons 712 00:43:18,115 --> 00:43:21,090 that project right into the hippocampus. 713 00:43:21,090 --> 00:43:24,730 And then there are pathways going back directly 714 00:43:24,730 --> 00:43:29,820 to the septum [? pronate ?] from the hippocampus 715 00:43:29,820 --> 00:43:33,500 and from the subiculum. 716 00:43:33,500 --> 00:43:38,590 And then this diagram also shows this major input 717 00:43:38,590 --> 00:43:40,230 from the entorhinal area. 718 00:43:40,230 --> 00:43:44,850 It's getting cortical inputs into the hippocampus. 719 00:43:49,070 --> 00:43:51,990 You get other kinds of plasticity. 720 00:43:51,990 --> 00:43:55,290 One of the most dramatic kinds of collateral sprouting that's 721 00:43:55,290 --> 00:44:00,250 been seen in the adult brain occurs in the hippocampus. 722 00:44:00,250 --> 00:44:02,100 And I can characterize it like this. 723 00:44:02,100 --> 00:44:04,390 Well, let's look at this one first. 724 00:44:04,390 --> 00:44:07,225 Here are some cells in the dentate gyrus. 725 00:44:07,225 --> 00:44:09,570 And here's a box. 726 00:44:09,570 --> 00:44:13,720 Each of that box corresponds to these boxes. 727 00:44:13,720 --> 00:44:21,070 And here I show inputs coming from other parts 728 00:44:21,070 --> 00:44:22,140 of the hippocampus. 729 00:44:22,140 --> 00:44:25,020 These are associationaries. 730 00:44:25,020 --> 00:44:29,410 Now, the entorhinal cortex, it projects up here. 731 00:44:29,410 --> 00:44:31,010 So what happens when if we remove 732 00:44:31,010 --> 00:44:33,800 all the entorhinal projections? 733 00:44:33,800 --> 00:44:38,110 You get collateral sprouting of these other axons coming down 734 00:44:38,110 --> 00:44:38,610 here. 735 00:44:38,610 --> 00:44:41,690 And so I show in red the sprouting that occurs. 736 00:44:41,690 --> 00:44:43,040 Major sprouting. 737 00:44:43,040 --> 00:44:45,800 It's a huge change in the projection. 738 00:44:45,800 --> 00:44:49,100 So if we look here, here's the terminations 739 00:44:49,100 --> 00:44:53,220 of-- this is that imagine the dentate gyrus cell here 740 00:44:53,220 --> 00:44:58,630 and here it's dendrites in every one of these boxes. 741 00:44:58,630 --> 00:45:07,550 So here's all the input from entorhinal cortex. 742 00:45:07,550 --> 00:45:10,770 And here's where the association axons terminate. 743 00:45:10,770 --> 00:45:12,740 So we get rid of all of these. 744 00:45:12,740 --> 00:45:14,580 That's what's shown here. 745 00:45:14,580 --> 00:45:17,800 All of these are eliminated. 746 00:45:17,800 --> 00:45:20,230 Here's what happens to the association axons. 747 00:45:20,230 --> 00:45:22,930 And that's what I'm showing here. 748 00:45:22,930 --> 00:45:24,010 Huge amount of sprouting. 749 00:45:24,010 --> 00:45:26,555 And it's not just the associationary area's axons 750 00:45:26,555 --> 00:45:27,920 that sprout. 751 00:45:27,920 --> 00:45:29,055 Other systems also sprout. 752 00:45:34,010 --> 00:45:37,340 So it's very dramatic adult plasticity. 753 00:45:37,340 --> 00:45:40,360 And now, people that have studied plasticity 754 00:45:40,360 --> 00:45:46,910 after-- in physiological situations, changes in synapse 755 00:45:46,910 --> 00:45:50,526 are beginning to find anatomical changes also. 756 00:45:50,526 --> 00:45:53,370 So it's not only after these drastic lesions 757 00:45:53,370 --> 00:45:56,010 that you get anatomical change in the hippocampus. 758 00:46:00,770 --> 00:46:05,360 And then you should go through this book. 759 00:46:05,360 --> 00:46:08,170 It goes through this amazing finding 760 00:46:08,170 --> 00:46:12,100 that we have a lot of memory consolidation. 761 00:46:12,100 --> 00:46:15,060 Consolidation of long-term memories 762 00:46:15,060 --> 00:46:16,750 for things that happened during the day 763 00:46:16,750 --> 00:46:21,040 are consolidated largely during the night. 764 00:46:21,040 --> 00:46:25,630 And I'm pointing out how the levels of these modulators 765 00:46:25,630 --> 00:46:27,360 changes. 766 00:46:27,360 --> 00:46:31,490 In waking, slow wave sleep, and rapid eye movement or dream 767 00:46:31,490 --> 00:46:34,710 sleep, here's the acetylcholine levels. 768 00:46:34,710 --> 00:46:37,830 And rapid eye movement levels are quite high. 769 00:46:37,830 --> 00:46:39,280 Even higher than waking. 770 00:46:39,280 --> 00:46:41,920 But in slow wave sleep they're very low. 771 00:46:41,920 --> 00:46:45,312 And this is the period where you get 772 00:46:45,312 --> 00:46:47,270 that consolidation happening. 773 00:46:47,270 --> 00:46:51,360 And the reason that people that have 774 00:46:51,360 --> 00:46:55,030 woven these for periods trying to explain why this occurs. 775 00:46:55,030 --> 00:46:58,070 We know it occurs. 776 00:46:58,070 --> 00:47:01,000 We think it's because during slow wave sleep, 777 00:47:01,000 --> 00:47:03,890 there's a lot more [INAUDIBLE] information 778 00:47:03,890 --> 00:47:05,395 from hippocampal structures. 779 00:47:08,305 --> 00:47:11,215 These are the hippocampal structures back to cortex. 780 00:47:15,590 --> 00:47:17,060 Showing you here. 781 00:47:17,060 --> 00:47:20,580 Whereas with high ACH levels, the same pathways 782 00:47:20,580 --> 00:47:24,904 are active but much less so with that modulator present. 783 00:47:27,630 --> 00:47:34,770 And a lot more-- the flow from neocortex to hippocampus 784 00:47:34,770 --> 00:47:36,380 is still strong. 785 00:47:36,380 --> 00:47:39,200 But the flow back to the cortex is 786 00:47:39,200 --> 00:47:43,140 stronger during slow wave sleep. 787 00:47:43,140 --> 00:47:47,900 Which could explain some of that memory consolidation. 788 00:47:47,900 --> 00:47:50,730 Because a lot of the-- it is retained 789 00:47:50,730 --> 00:47:54,606 in the hippocampus itself initially. 790 00:47:54,606 --> 00:47:57,210 But the hippocampus doesn't have the capacity 791 00:47:57,210 --> 00:48:00,305 to retain all our long-term memories forever. 792 00:48:00,305 --> 00:48:01,586 It's stored in the neocortex. 793 00:48:01,586 --> 00:48:06,920 And we know that from studies of electrical stimulation 794 00:48:06,920 --> 00:48:09,310 of the human brain during neurosurgery, 795 00:48:09,310 --> 00:48:14,340 from studies of damage in neocortex. 796 00:48:17,030 --> 00:48:20,870 And this just shows you another way people have represented 797 00:48:20,870 --> 00:48:24,050 these pathways between entorhinal cortex 798 00:48:24,050 --> 00:48:25,525 and hippocampal formation. 799 00:48:30,860 --> 00:48:34,400 So neocortex, the hippocampus is critical in the whole way 800 00:48:34,400 --> 00:48:37,170 this thing works. 801 00:48:37,170 --> 00:48:39,110 And we know that both theoretically 802 00:48:39,110 --> 00:48:43,030 and from actual anatomical studies of various mammals. 803 00:48:43,030 --> 00:48:45,180 And I've just given you various pictures here. 804 00:48:45,180 --> 00:48:47,500 You'll see some humans. 805 00:48:47,500 --> 00:48:51,540 Some of you will be interested in the way it looks in imaging. 806 00:48:51,540 --> 00:48:56,610 This just shows where the amygdala is there. 807 00:48:56,610 --> 00:49:00,465 And here you see both the amygdala-- the almond shape 808 00:49:00,465 --> 00:49:07,020 right here-- and hippocampus in a sagittal view in an MRI scan. 809 00:49:07,020 --> 00:49:10,740 The radiologist become very adept at finding 810 00:49:10,740 --> 00:49:13,515 all these structures even with the low resolution 811 00:49:13,515 --> 00:49:17,850 you get in these types of images. 812 00:49:17,850 --> 00:49:19,230 But what we'll do next time. 813 00:49:19,230 --> 00:49:22,894 I'll just review at the beginning the hippocampal stuff 814 00:49:22,894 --> 00:49:24,810 but I don't want to spend a lot of time on it. 815 00:49:24,810 --> 00:49:27,725 I will post these slides early so we 816 00:49:27,725 --> 00:49:32,780 can study more the amygdala here and its importance 817 00:49:32,780 --> 00:49:34,110 in this whole system. 818 00:49:34,110 --> 00:49:37,910 And then the structures in the basal forebrain anteriorly 819 00:49:37,910 --> 00:49:40,600 that the amygdala's strongly connected to. 820 00:49:40,600 --> 00:49:41,880 OK? 821 00:49:41,880 --> 00:49:45,840 So I'll post all these online, but also 822 00:49:45,840 --> 00:49:49,750 post the next class's things just 823 00:49:49,750 --> 00:49:52,760 to make sure we can get through it during the class.