The fourth installment in our series concerning the intra-related connections between space and memory concerns the hippocampus. I'm going to be telling you about both human and animal studies that converge to provide a really interesting picture of the connections between these two important aspects of human cognition. The human side of the story centers on a particular patient, a very famous patient known as HM. His real name was Henry Molaison. This is a picture of HM taken in the 1950s when he was a young man. Dating from the age of seven, when he had a bicycle accident, HM had suffered from intractable epilepsy. In an effort to cure this epilepsy, surgeons remove the hippocampus and much of its surrounding tissue. This surgery was effective at controlling his epilepsy, but it came at a terrible price. After HM awoke from the surgery, he suffered a severe deficient known as anterograde amnesia. That's a fancy way of saying he could form no new, what are called, episodic memories, dating from the point in time at which he lost his hippocampus. Episodic memories are the memories that we think of as being memories. Your ability to remember episodes from your life, whether or not they occurred earlier today, last week, or when you were a child. These are memories for episodes and experiences. My memory for renting skis is an example of episodic memory. HM wouldn't have been to remember the person in the ski shop even with a very minor interruption like, perhaps, going out to the car to get his wallet. The nature of HM's deficits have been studied extensively by neuroscientists. HM was very generous with his time and contributed greatly to our understanding to the neural basis of memory. And it's tragic to think that as time went by, his own face would have been less and less recognizable to him in the mirror. He died in his 80s in 2009. Based on the deficits exhibited by patient HM and many others, it seems clear that the hippocampus is essential for forming new, long-term memories of the episodes and events of our lives. But there is more to the story. The plot thickens when we start to consider evidence from animal studies, particularly animal studies involving rats. These studies have broadly confirmed a role for the hippocampus in, in memory. But particularly when the memories are connected to a spatial location. This has been assessed using a task known as the water maze task. In this task, rats are placed in a tub of water that is slightly cloudy. And they have to swim around until they find a hidden platform underneath the surface of the water. When they find the platform, they can stand up and stop swimming. Rats with an intact hippocampus are easily able to remember the previously learned location of a, of this underwater platform. But rats with hippocampal lesions are impaired on this task. In addition, studies of the neural signals present in the hippocampus implicate the hippocampus for a role in encoding the position of the rat in the environment. This is also called a cognitive map, and it involves a particular type of response pattern called a place field. Hippocampal place cells have these place fields, and it involves being sensitive to the rat's location in the environment. This is a little map of how a particular neuron might have responded. With the more bluish colors indicating more activity and the more yellowish colors indicating less activity. As the rat moved about this environment, the activity of hippocampal place cells changed firing. The activity of hippocampal place cells vary with location. So this particular neuron responded more when the rat was in this lower left hand area of the enclosure. On the next slid,e there's a video of this and you know the drill. Listen for the pops and the clicks that indicate action potentials and try to figure out where in the enclosure is this particular neuron's place field. [BLANK_AUDIO]. Well, what do you think? Was it more at A, more generally at B, at C, or at D? Try your hand on the in-video question. Now the hippocampus' representation of place within the environment is a little bit different from what we see in areas like primary visual cortex. Neurons are not topographically organized according to where their placefields are. A neuron with a placefield at one end of the enclosure could be located right next to a neuron with a placefield at the complete opposite end of a particular environmental space. Further more, each neurons place field is not unique. The individual neurons can exhibit place fields in more than one environment. Neurons in the general vicinity of the Hippocampus, also participate in encoding other aspects that can be important for cognitive mapping. Neurons in the Entorhinal cortex, for example, show a property related to heading, that is, what direction are you facing. These neurons are called head direction cells, and they're exactly what they sound like. Their activity patterns vary according to what direction the rat is facing. This is a schematic graph of the activity pattern of a head direction cell, and perhaps when the rat is facing north, the neuron might respond very weakly. When the neuron is facing somewhere southeast, the neuron might exhibit a stronger response and again, a weaker response when the rat is facing west. So the best direction here would be southeast. And there are other neurons in the population that are tuned for the other directions. It's like the rat has a little compass in its head keeping track of which way is north. Well, it's not just place and heading, but there are also signals that seem to be related to the distance travelled. These neurons are also located in Entorhinal cortex, and they're called grid cells. They have activity that varies with location, but there are many peaks to their response patterns. But the peaks are evenly spaced. So you might get high activity there, there, there, there, there, there, and there. And notice that these are all a certain distance apart from each other. So by keeping track of the pattern of activity in the grid cells, other circuits in the brain might be able to determine how far the rat has traveled. So the presence of these signals that are related to navigation and understanding where you are in the environment, together with the evidence from lesion studies, that the hippocampus and its surrounding structures are important for performance of memory tasks, supports the idea that space and memory are fundamentally linked in the brain. We've already talked about how important memory is for navigation. It is only by remembering things like, how many steps you've taken or long you were in motion along a particular direction, that you can estimate your position in the environment. But flipping things around. The things that we experience as episodes or events in our lives, they always occur in spatial locations. That's, in a sense that's a trivial thing to say, but it provides the opportunity for keeping memories organized. It may be that our location in the world serves as an index to retrieve those memories. If we are thinking about the things that are connected to the place where we are, we are probably thinking about the things that are most relevant to us. So when I went back to that ski shop, I was able to retrieve the memory of the person who had helped me the previous year. That information was useful to me because I was back at the same place. That wouldn't have been useful to me in any other setting. So you can think of spatial location as possibly being the filing system for memories. We can't organize memories alphabetically, but we can organize them according to the place where they occurred. If you've ever been back to a high school or college reunion, you may have been overwhelmed by a flood of memories that you haven't thought about in the intervening years since you were a student. This may be because you hippocampal place cells are allowing you to retrieve memories connected to that spacial location. Well, in the next video, we're going to take this one step further and think about the connections between spatial processing in the brain and other aspects of cognition. Namely, thought itself, our ability to think and reason about concepts varying from concrete to abstract.