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Okay so, let's go now, from the axon and dendrites, and the different types, to the synapse.

So, again, let's look at these two reconstructed neurons. Let's call the blue neuron the one with blue dendrites, and the green neuron the one with green dendrites and yellow axon. So now, these two cells. And I will call the green. Neuron with it's white axon the presynaptic cell. And I will show you that this green cell is making contact, synaptic contact to the blue cell. For example, if you look very carefully here and here you will see that the, that the, that the yellow axon is coming very, very, very, very close to the blue dendrite. And I can show you later, but this you cannot see using this level, this resolution, that there is indeed a synapse there, and we'll show you what synapse means. So a single presynaptic cell, can make synaptic contacts at several locations on top of the post-synaptic cell. In this case, I'll just show you three cases, three synapses. So you can think about the yellow axon going through the blue dendrites, occasionally making this particular, unique contact unique synapse between the yellow axon to the blue dendrites. And if you zoom in very very much using electron microscope, and this is only light microscope. Electron microscope you will see something like that. So you will see the axon. This is a very, very short bouton, varicosity of the axon. The pre-synaptic element. You will see the post synaptic dendritic spine that we spoke a lot before about. So, this is the dendrite and this is the little spine. One single spine we see here emerging from the dendrite, there is a little neck and there is a little head of the dendrite, of the spine. And the connection between the axon and the dendrite is called a synapse. So the synapse consists actually of three elements. The pre-synaptic axon, the post-synaptic spine or dendrite, and there is also a gap between them.

So Harmonica Hall was right. They don't, you can see it here, but they don't physically touch each other. There is a gap, a very, very small gap, very, very small gap that you can only see in electron microscope. So Harmonica Hall no chance using light microscope to see this level of resolution. And let's schematically see what happens. So there is an axon going through, a piece of an axon going through. There is a dendritic tree with spines, with andritic spines. Each spine receives a synapse, for example, this axon makes a synaptic contact between the axon. And the dendritic spine. The post-synaptic dendritic spine. I just can tell you that, we'll talk a little bit more about this later. But this specific collection between the axon and the spine are typically of the excitatory type. Usually these axon try to excite the post-synaptic dendrite in the post-synaptic cell. But if we go to a higher resolution, EM, electron microscope, a very high resolution electron microscope, we see the axon here. And if you zoom in, you can see these little vesicles. These little spheres. These are the spheres, the vesicles, that consist of the neurotransmitter. So here, you may have 5000 molecules of neurotransmitter, let's say glutamate, or let's say acetylcholine of serotonin. So this is the presynaptic part of the synapse. The axon and inside this bouton, this varicosity, you have the vesicles consisting of neuron transmitter. Post synpatically you see the dendritic spine. Here in the head of the dendritic spines, there are receptors. The receptors here, the post synpatic density consists of receptors that will interact with a transmitter if the transmitter. Will be delivered, will be transmitted through this little gap, the synaptic gap. So you can see that the axon and the dendrites do not touch physically, each other. There is this gap in the presynaptic side.

There are, these vesicles full of transmitter. The post-synaptic site, the spine, there are receptors that are waiting, so to speak. To receive the transmitter. So this is a synapse. When I say synapse, I mean these three parts. The pre-synaptic, the gap, and the post-synaptic, the dendrite. And. And now I'm connecting activity to structure. We know that the axon already, we know that the axon carries spikes . So in the axon, when there will be activity. Spikes will arrive into this spot. Okay, and this spike, as I said, is either there or not. And when the spikes arrive to this reg to this region, the spike itself succeeds somehow, in a magical way so to speak. Succeeds to make the transmitter being released to the gap, and then to the post-synaptic dendrite. So, the spike is the trigger for releasing mechanism of the transmitter from the vesicle into the gap. Post synaptically, if you recall from the dendrite, you will see another signal. So, pre-synaptic in the axon, you will see a spike. Post synaptic in the dendrite, you will see this other signal. The excitatory synaptic potential, in this case. So, you see now the two types of signals in the brain. The two major type of electrical signals. And we'll start to talk about this signal in the next lesson. The active spike, the action potential, the zero one. The all-or-none element, which exists or does not exist, this is in the axon. In the dendrite, you will see the post-synaptic potential. It could be excitatory post-synaptic potential, which tries to excite the post-synaptic cell it could be inhibitory post-synaptic potential with a negative sign, which will try to reduce activity. So these are the two major signals. And then the major difference between them is the fact that this is a digital signal. It either occurs or not. So it is zero one type of signal.

This signal is a graded, is an analog signal. The synaptic potential is an analog signal. It can become as big as this, few milli volts, more, more or less. So this is a graded signal. So you can see that the synapse is a unique transmission line, or communication device, it communicates on one side a digital signal, to an analog signal in the other side. We can think about the synapse as a digital to analog converter. And this analog signal post synaptically may gain different amplitudes. So I can speak about strong synapse. Meaning that for a given spike the synapse may generate large postsyanaptic potential. And I can think about weak synapse. So for the same spike, you will get a weaker post-synaptic signal. Smaller, or maybe even nothing. I can speak about the silent synapse. Where the action potential here does not release vescicles. Does not release transmitters. So if we would record here, you will not see voltage change, you will not see potential. This will be a silent synapse. The synapse is a communication device. And the strength of the synapse is the strength of the ratio between the pre synaptic all or none spike to post synaptic greater potential. So let's look at it a little bit further. Just to complete the issue of synapses. The schematic view. This is an axon. The action potential travels along an axon. So the axon branches and this is just one of the recoursity or one button. And in this button there are all these vesicles consisting of transmitter molecules. These are transmit schematic transmitter molecules. And being released when there is an action potential here. They are released through the gap, through the synaptic gap. They are here in the gap, which is of course much smaller, and post-synaptically, in the dendrite, there are these receptors who are trying to catch, to receive. The transmitter.

So these are the vesicles. These are the receptors. Sorry. These are the vesicles, these are the receptors. And the synapse, as I said, is a transmission line between the axon firing spike, and the dendrite receiving the transmitter, responding. With generation of post synaptic potential. So let's look at it in a general way. An action potential travels here. It encounters a vesicle in the pre-synaptic axonal button. Often, optically you have a dendrite with receptors. If the action potential reaches here, the vesicles, as you will see, are being fused into the membrane of the pre-synaptic axon, so suddenly, the vesicle is open. And the content of the vesical, the transmitter, can be now cross through, into the gap and being now affected or caught by, interact with the receptor. And you will see when we talk about the, the electrical activity, you will see that these receptors enable the flow of electrical current into the dendrite generating the post synaptic potential. So it's from pre-synaptic spike through a chemical interaction, between the presynpatic element and the post synaptic reception receptors. These are chemical interaction. The synaps is a chemical entity. But remember the pre-synaptic there is a electrical activity the spike. Post synaptic there is electrical activity. The post synapstic potential and the in between is a chemical that inter. That the neighbors interactions between the spike and the post synapse potential. This is the magical synapse. Because you may know that this synapse is really, really the most fundamental unit in the brain that enables memory. We'll talk about memory. On the fifth I think lesson. It enables the effect of drugs. Into this region, because it's a chemical element. And you can manipulate the chemistry in this region by certain drugs. If certain drugs is missing, you can give this drug, so that the synapse will direct better, will function better. So this effect the fact that it is not

all electrical. But there are these inter-, interact intermissions, gaps of chemical elements makes the nervous system very plastic, accessible to effects of drugs and also effects of changes in the connectivity. And so Harmonica Hall again, when he said that they are not connected, if you don't know of course that this is exactly where the changes in the nervous system. The fact that you can learn, the fact that you can effect the nervous system in many, many ways is due to this magical device that digital to analog through chemical interaction. It's a magical device. That was really developed many, many, many, many, many years ago. I mean very simple elements already use this device but our synapses of the mammalian world are very sophisticated elements and that being a very, very sophisticated plastic changing interaction between one cell to the other cell.

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