So this was comment number one. The comment about the need to move, which is amazing. The need to move physically, the most primary aspect of behavior is movement. This movement is essential for the development of other senses. This is called the action perception loop. And then you perceive, and by moving and perceiving, you improve your movement, or you develop a better movement and so on. So it's a loop. The other remark, before I go into the mechanism of learning, the other, sorry, the other remark is about reality. What is reality? Is there a reality there? Of course there is some physical reality there, so we believe, but in order to develop concepts about the reality you actually use a very, very sparse, very, very little information. Like the one I showed you about the cow. And based on memory and based on learning, you'll eventually build some reality. You'll believe that there are trees there. Of course there are not trees there. Trees is a consensus between us. There are faces there, there is some structure. We agree among us through learning that this is a face. One of the most amazing example really just to show that you build reality for a very minute information. You may reconstruct a reality that is agreeing among us. And this is the case of cochlear implants. In cochlear implants, in case of people that have difficulties in hearing, you really get into your ear noises. Very, very, very, strange noises, but then you learn slowly slowly, as the deaf, you learn slowly slowly, to interpret what goes into your ear, activate the cells there, all the different cell types, eventually goes to your cortical area that interpret these sounds eventually, with the very manute, strange sounds, you start to hear father, mother, face. But this comes from a very, very sparse, very, very incomplete information. So the brain reconstruct information. And here, it's a very, very good example, but this is true always. You see something and immediately the need through learning, or through your need to categorize the word you grasp something. And you believe that it's there. Okay, so after this introduction, I would like to go really into the brain. Into the mechanism of the brain. So, we all know the basic mechanism. We know that the brain is built for nerve cells. We know that the brain carries electrical signals. Action potential, synaptic potential. We already know some about this mechanism, and the question is how these anatomical and physiological mechanism support learning and plasticity. So this is a repeated word, plasticity, saying that the brain is plastic. It's not rigid, but it's changing, it's plastic. So what is the underlying mechanism of plasticity? So we can not avoid always to go back to the big father of anatomy. In this case remember Ramon Y Cajal, remember the two controversies, the big controversy between Ramon Y Cajal the Spaniard and Camilo Golgi the Italian. And Cajal said already, more than a hundred years ago, the following sentence. There is a notable increase in intellect among men. He should have said men and women of course. Among men dedicated to deep and continued mental experience. So he realized that there is learning. And he asks, so what is the underlying underpinning of learning? He said, moreover, notable talent and even of a true genius can coexist with a medium or smaller sized brain than those of normal weight and dimensions. He was right. We know that Einstein was a great genius. Had a very small brain, 1.2 kilograms which is much smaller than for most of us. There is no correlation between weight of the brain and intelligence. But then he said the following, in the first case given that new cells. Cannot be produced. Nerve cells do not multiply as do muscle cells. So said Cajal, he was wrong here. We shall discuss it in at the end of the talk. It can be supposed that cerebral gymnastics, this is a very beautiful term, cerebral gymnastics. You're doing brain gymnastics. Will lead to the development of dendritic processes and axonal collaterals and branches beyond that normal observed, forcing the establishment of new and more extensive intracortical connections. So Ramon Y Cajal says. Fundamental thing. He said there must be some change in the brain underlying memory and learning. You cannot learn something new without some fundamental change in the brain. If nothing happens to the brain like nothing happens to my computer now. That changes the computer, it doesn't learn anything. He said something that is wrong, then I will show you later on because these are new results, he thought there are no new cells, new nerve cells, he thought. And like new muscles, that you knew when you practice, the addition of muscle fibers. He said no nuises, no new nerve cells. So what could underly learning and memory? Existing cells, existing neurons make new branches, make new connections. He didn't know about new synapses. This is what we called structural plasticity. The reason underlying structural change in the brain. Underlying new learning and memory. Ramon y Cajal was very poetic, very romantic, very poetic and he said, the cerebral cortex, he knew that this region of mammals of us is very important, the cerebral cortex is similar to a garden filled with trees, the pyramidal cells, we already saw the pyramidal cells before, which, thanks to intelligent culture, thanks to the fact that you need to learn, can multiply their branches, they don't multiply themselves, but only the branches, sending their roots deeper and producing more and more varied and exquisite flowers and fruits. He means spines. He means dendrites. There are no fruits in the brain, but that is a very poetic way to say there must be some structure of change. So that's what Ramon y Cajal said. Indeed today with new techniques we study the changes in the brain underlying memory and learning. And in particular, this region the hippocampus, which is a very important region for learning and memory. This particular region is very, very much in the focus of learning and memory in brains. So this is the hippocampus, in this case of human, but of course rats, and cats, and monkeys also have hippocampus. It is called hippocampus because it looks, the structure of this region looks like the structure of hippocampus. We know that very fundamental learning processes are happening in the hippocampus and we know also that the hippocampus is built from unique type of neurons. We know a lot about the synopses there, the connections. We know a lot about the anatomy of different regions of the hippocampus, the CA1, the CA3, and other regions. And so a lot of the learning about the brain, about the capability of the brain to learn, to change, is really performed on hippocampus. But not only hippocampus, also for example, on the cortex what is the underlying changes? What is the mechanisms? What are the rules for learning implasticity in nervous tissues? This is the question that we want to pursue. So let's go to basically three possibilities. Three possible mechanisms underlining learning and memory. Subserving, learning and memory. The first possibility that Cajal did not accept, did not know that yet that it does exist, is that new cells grow are born. And then new functional networks are being generated because there is a set of new cells. There is a set of new networks and this new network underlies new memory. So you learn something new now, let's say then there is a set of new neurons, a group of neurons, a network that when this network is active then the new item pops out. This is structural plasticity because a new structure, new nerve cells, new networks, being born under this assumption. This is assumption possibility number one. Possibility number two and that's the possibility that Ramon y Cajal mentioned but of course it didn't speak about synapses but the possibility is that new synaptic connections, new spines are growing, new axons, new synapses are formed, new functional networks are being created. Not because you have new nerve cells, but because there are new connections. I am now connected to somebody who I was not connected before. He's connected to somebody else just because he formed new synapses. And functionally you form new networks not with new neurons, but with new synapses. So that's possibility number two, and that's again structural plasticity because there is a new structure, a new synapse, a new axon, a new dendrite, a new spine. Structural plasticity. But there is also the possibility that is called the functional plasticity. Functional plasticity and the idea here is that existing synapses become stronger or weaker. It's not that you build new synapses but you use old synapses in a different way. A synapse may be strong or weak. We'll discuss it in a second. We already mentioned it. A synapse may transfer information, transmit information, better or worse. So maybe existing synapses may change their efficacy and this functionally again generates new kind of active networks because now I'm most strongly connected to you. You are most strongly connected to somebody else. And you form a network, not because you address or you generate new synapses but you use old synapses. And make them stronger or weaker and function of the network changes. So these are the three basic possibilities really. Either you have new nerve cells underlying memory. Or you have new connections from existing cells, in between existing cells. Or existing connections become stronger or weaker, and this underlies changes in memory.
