Okay. But let me go backward for a second, and still go back and discuss the controversy.

The controversy between this two big giants, Camillo Golgi who I just mentioned developing the technique to stem cells. Santiago Ramon y Cajal, who used this technique. Both received the Nobel Prize for their huge, fantastic anatomical discoveries, detecting cells, detecting networks, detecting structures within the nervous system. And especially, Ramon y Cajal was a very, very good painter, a very, very good artist, and actually, he wanted to be an artist. But eventually became a great scientist. But he was an artist as well. As you can see, these are original drawings by Ramon y Cajal, sitting in front of his very, very old poor microscope. Looking at the microscope again and again. At different pieces of the nervous system. From the spinal cord, to the cerebellum to the cortex. So, here is the cerebellar neurons and this is the cortical networks here and there and other regions. And this is the retina inside the eyes. The eyes with all these different layers. So, Ramon y Cajal was really a giant in the sense that he liked to draw. And he liked to characterize structures. And he went to different regions in different animals. Humans, rats, and others, and to the most simplest system and try to really draw. What he sees. And this is using, as I said, the method of Golgi to stem cells. Luckily as I said they, they are really very sparsely stained. So you see one, and then another one, and then another one. Not everything is being stained, because otherwise it would be completely black. So, about 1% or less of the neuron in this system are being stained and this enabled the harmonic hand to follow, to draw one and then another one and then another one. So Ramn y Cajal, when he just looked anatomically at the system, he did the

following, which is a big jump conceptually. So he see a network, in this case, cortical network. And he sees cells, so this is one cell and this is another cell body. And you can see the dendritic tree, and if you zoom in as we should do later you can see this little appendages, which we will call spines, dendritic spines but he saw that when he drew it. And then he invented something, almost. Almost invented something, just by looking at the anatomy of the system, he said. I think that information flows, information flows. But he didn't record any information. He just thought it. Information flows through a process. It is an axon. A long process. In this case coming from the white matter into the cortex. From the thalamus into the cortex. So, we draw this little arrow here, say that information flows this direction, along the axon. And then it did another jump. It said from this axon to this dendrite, there is a communication. It could not see any communication, but it thought that information must flow this direction. And then it means that they must be somehow connected to each other. Through this link and from this dendrite receiving the input from the axon. Information flows this direction from the dendrite, to the cell body of this post neuron. And then, from the cell body to the axon of this neuron. And then, from the axon of this neuron, to the dendrites of the next neuron. So this, the arrows, these arrows, showing information flow. Direction of information flow. Is a pure, so to speak, invention of Ramon y Cajal, because it could not record any activity. He just could look at the anatomy. But this was his, the beginning of his concept that one neuron and the second neuron are separated somehow. And so he can call each one of them a cell, a nerve cell, later on, a neuron. Okay, so this is the neuron doctrine by Ramon y Cajal, and the other, what he called the theory of dynamic

polarization. He says, that the, the, this, the receiving cell, the receiving dendrite are first polarized, somehow polarized. Electrically probably, I've polarized this region, because the input comes to the dendrite. It polarizes here, and then the polarization, flows from the dendrite to the soma. And then to the axon and so forth. So, this is called the theory of dynamic, of dynamic polarization, by Ramon y Caja. So, to summarize Ramon y Cajal functional view of neurons, he says the following, dendrites are the receptive, the input device. They receive input from other neurons, and axons are the sending, the output device of neuron. And today we actually basically accept for more than hundred years. We accept this concept we agree with Ramon y Cajal, Golgi did not like this description. He did not feel that there is a distinction or separation between one neuron to the other. He thought that they are all connected physically. They touch each other and it's one big connected network. So he didn't agree to the concept of neurons. And this was probably part of his romantic view that the brain is something different than any other system. How could the brain, how could the feelings, how could emotions, how could the love of opera, and everything else that we create, relies on individual elements like this. Connected to each other. Carrying information, it must be something continuous. It must be something different. Than any other system. It must be something different. That's what Cajal said, and both essentially fought on the podium, in 1906 when each presented his Nobel lecture. Ramon y Cajal spoke about the neuron doctrine. About the separation of cells from one another. He did not know how they talked to each other but he realized there must be some connection. And Golgi said, my honorable colleague is mistaken.

It's a very nice theory, but it's not the correct theory. So today of course, we accept Ramon y Cajal concept. The nervous system is built essentially, from separate elements connected to each other by synapses, which we are going to discuss in a second. But just before that, I wanted to show you a modern view of neurons. Because today, we can stain and reconstruct using computers, using modern microscope and techniques, staining techniques. This is an example, a beautiful example, from Kevin Martin, in Universite Zurich, where you can see very clearly an individual cell in the cortex in, this case,[UNKNOWN], the green element is the dendritic tree. You can see that the dendritic tree is local, relatively local. And this is about 1 mm from cell body to the tip of the dendrite. And you also can see the axonal tree. The red and the white dots, the axonal tree. Axons can go sometimes out, very far away, or sometimes more local. So you can see the red tree is the axonal tree and the white points, the white dots in, on the axon are what we call the varicosities. You will later see that, in each of these little varicosity, or sometimes called buttons. In each of these buttons, there is the neurostransmitter. The chemical transmitter, that interacts through the synapse with a post synaptic. With the other element, with the other cell. Through this little spot, the synapse. So you can see an axon full of spots. Sometimes 5,000 synapses, 5 times 5000 spots within a given axon. So this is a typical view of a neuron. The dendritic tree, which is local, the axonal ramification branching. Which could be rather globlal, sometimes go to another part of the brain. Sometimes makes a lot of synapse locally.