Why we pay so much attention to anatomy and why we put so much time on studying the different brain areas, different shapes. Or these difficult names of our brain because anatomy can really help our study. Here I use one example of study LTP, long-term potentiation, just to demonstrate the significance of studying anatomy. So this is our hippocampus, we mentioned before. We said that Brenda Miller, the famous doctor discovered with her patients [INAUDIBLE] the importance of hippocampus to learning and memory. So this is a brain slice from mouse hippocampus. And this diagram shows the structure, the very simple structure of hippocampus. So inside of hippocampus, we have very simplified structure. One is called the dentate gyrus here and dentate gyrus from one synapse connect to a region called C3. And C3 from another one synapse connected to another region called C1. So only three major regions inside of this hippocampus, dentate gyrus, C3 and C1. And then they all connect to each other dentate gyrus to CS3, CS3 to C1. And then there's only two synaptic connections inside of this hippocampus. So another character of this hippocampus is the cells, the neurons inside of hippocampus are very aligned. They stand by each other very tightly. For example in CA1, there are lots of primary neurons and in these neurons they aligned to each other very neatly here in CA1 region. So from this histostaining graph we can see in this CA1 region, there are lots of cells, lots of neurons, tight packed in this region. And then also for CA3 and then the DG, dentate gyrus region is here. So in hippocampus, it's a very simple neural architecture structure. So the study of LTP. So first of all I need to introduce you the concept of LTP, long term potentiation. So the discovery of long term potentiation, we need to back to 1970s by Tim Bliss. He recorded with hippocampus slices, he recorded a phenomena called long term potentiation. So during long term potentiation, what he does, what Tim Bliss does is before he will put a electrode a stimuli electrode. For example in stage 3 region and put a recording electrode in CA1 region. So because from CS3 region, two CA1 region, there's one synaptic transmission here. And then if we stimulate CS3 region, we can record a response at CA1 region and then later on Dr. [INAUDIBLE] will tell you why. After learning the synaptic transmission, okay. So we stimulate CS3 region, we can’t halfway response at CA1 region very peacefully, very faithfully. And then what Tim Bliss did is stimulates CS3 region and then record from a CA1 region. And then he will record a response and then put it on this bar graph here and then after recording for 30 minutes baseline level. Until the slices get stable and then he will get a very high frequency stimulate. Normally we call it trained stimulate. This stimulate can be 2,200 hertz or 100 hertz for five seconds and after this, trained stimulates after this very high frequency stimulate. Templates will back to this, the real back to the stimulates as before or stimulate the brain slice every seconds. And then he will record that response. And then interestingly, after he get back to the stimulate before he used, he will record a enhanced response at CA1 region. And then this enhancement will last for very long time. For several hours, sometimes people can record LTP for weeks. So this is a very typical recording of LTP, let's look at the black dots first, the wild type one. Like before this zero point is where we give the [INAUDIBLE] stimulates. The high frequency stimulation. Before this stimulation, we give stimulation every seconds, like this one. We give stimulate and we record a response, record a black dot here. And then next second we give one stimulation and then we record one response. And we put this black dot here. Because we give all the same intensity of stimulation, so the response should be roughly the same. And then we record this for 30 minutes. This zero point will give the high frequency stimulation and then we get back to this stimulation once per second as before. Now at the CA1 region, we can record a response with enlarged amplitude here. For very long time here for example, this example is for 60 minutes for one hour. Now with this LTP model where you can do this LTP recording either in wild type animal brain slice or in mutant animal brain slices. Because like learning and memory especially memory is a very fasicnating topic for very long time in neuroscience field. People always want to figure out the mechanism of memory. Because memory sometimes can last very long. For example, the memory of your own name and birthday can last your life long, say like 80 years. So, the underline mechanism, biological mechanism has to be a prolonged process, right? So that's the rational of people looking for the mechanism of memory. So people have always been looking for a very long process. When LTP was produced by Tim Bliss people were very excited. People think this wow, this enhancement or this enlarge response can last for several hours. This process is very long, right? So people nowadays people even, there are lots of people believe LTP is the basis, is the neuronal basis for learning and memory. And some people even memory LTP and indicating the learning and memory ability of the certain animal. So there's argument although this process is very long. There's argument for this rational of LTP being the basis or the mechanism of learning and the memory. First, LTP is low, it can last for hours and then nowadays with our updated recording technique we can record for weeks. But it's not that long like some memory, I just said some memory of your own name and your own birthday can last for 80 years. But LTP cannot last for 80 years, it can last for weeks but not months or years, right? So LTP is not that long. So people argue the basis of this concept of being the mechanism of learning and memory. So anyway, besides that the LTP is a very useful module to study learning and memory still. This is Tim Bliss when I met him in 2006 in London. This is his institute celebrating his 80th birthday and the institute for him had a party and then this tie, here he wear this tie. So called institutional tie and then you can see the pattern of this tie. But I can tell you the pattern on the tie is hippocampus, this small ones, yeah. Just to credit him for discovering LTP Bliss hippocampus slice. Let's go back to hippocampus slices. So this is hippocampus slices, by studying hippocampus and the substructure of hippocampus. We can know the hippocampus itself has great advantage for Tim Bliss to discover LTP. First, the alignment of neurons in each area. For example, CA1 region, CS3 region, are very neat. Old neurons align to the same way. And each region, they have lots of neurons, they have lot number of neurons. So if you stimulate one region, it is very easy for you to record response from another region very peacefully. In the second, the pathway, the transmission pathway itself is very simple. From dentate gyrus to CA3, from CS3 to CA1 region. So if you stimulate dentate gyrus, you can record response from CS3 for sure. If you stimulate CS3, you can record response from CA1 for sure, so very simple pathway. So these features from anatomy give Tim Bliss the greater advantage to study or to discover LTP with the hippocampus slices.
