Welcome back. So now we've talked about signaling along the length of neurons. We've talked about signaling along dendrites and cell bodies, which are using graded potentials. Along the length of axons, there's going to be action potentials that are used to communicate along the length of axons. Keep in mind too that neurons can be very long cells. For instance, the axons that control the muscles in your foot have their cell bodies sitting in your spinal cord. They send an axon all the way down to your foot to innervate the muscle. So the axon potential has to travel all the way down your leg along that axon to control your muscles. That gives you a sense for how quickly these action potentials have to move down the axon to be useful. Now what we want to talk about is focused more on communication between neurons. That's what this session will be about. That's going to be accomplished in large part through chemical synapses, which we've talked a little bit about already. You're going to have the terminus of an axon, the end of an axon, synapse with some other cell. Synapse meaning that it gets very, very close to it, but they don't quite touch. The downstream cell, or what we call the post-synaptic cell could be another neuron, certainly. It could be a muscle cell, or it could be a cell from another organ, that doesn't matter. The idea is that the two cells come very close to one another. The action potential we already know is going to travel down the axon and come to this terminus. In the end of the axon we have voltage gated calcium channels. That action potential is going to cause them to open which lets calcium enter the axon terminus. That calcium will act as a signal to allow vesicles that are full of neurotransmitter to fuse with the plasma membrane and dump out here into what we call the synaptic cleft. So this is where the nervous system is very similar to the endocrine system. The endocrine system releases hormones into the blood. Here the nervous system releases neurotransmitters into the synaptic cleft. However, you know that the hormones that get dumped into the blood, have to travel all the way through the body and diffuse throughout the body to get to their target. So that's going to take some time. Where here we have a very small distance that the neurotransmitter has to diffuse, across. It's going to be released in really large quantities into this small space. Whereas we know endocrine hormones are going to become very dilute once they're put into the circulation. That's going to make neuron chemical synapse very rapid. Tons of neurotransmitter will get released into the synaptic cleft and then it binds specific receptors which are often ligand gated ion channels. We'll talk about this some more with specific examples. That's going to cause some sort of change in the downstream cell. If the downstream cell is a neuron and those are ligand-gated channels, then we're going to cause a graded potential in this downstream postsynaptic cell. Another thing to keep in mind is that this synapse is going to have some way of terminating the signal. By, for instance, degrading the neurotransmitter that's in the synaptic cleft or by taking it back up into the axon terminus. Some way of getting rid of that neurotransmitter. So that if signaling happens again, it will cause another response in the postsynaptic cell. This is the same figure that we've talked about before, where we can have excitatory or inhibitory synapses. An excitatory synapse is going to be one that causes a depolarization of the membrane in that postsynaptic cell. We call that an Excitatory Postsynaptic Potential. It's just a fancy name but it kind of make sense. That's going to be a graded depolarization. That's what synapse 1 and 2 are causing. That's often going to be due to an influx of positive ions, opening sodium channels, and sodium will rush in. Then we can also, as we've already discussed, have an inhibitory postsynaptic potential which is going to cause a graded hyperpolarization as is seen with synapse number 3. That's going to be due to either an inflex of negative ions like chloride or an efflux of positive ions like potassium. We've already talked about how these are going to be graded potentials and that they're going to be additive. Another thing that we need to consider is the fact that neurons can form different types of networks. We can have systems that are divergent, which means that one neuron can control several downstream neurons. This would be useful if you wanted to amplify a signal or if you want to control several different cells or processes. Also you can have convergent neuronal networks which is when several neurons send inputs to a single neuron. This would be an example when this downstream neuron is getting inputs, and it's summing these graded potentials to decide whether or not to fire an action potential. We'll be talking about these later in the course but just to give you an idea of the power of these neuronal networks and of these inhibitory and excitatory synapses. we're going to talk a little bit about lateral inhibition. This occurs when neurons inhibit their neighbors. What that can allow us to do is better perceive what's happening. In this case, when something like a pencil is touching our skin. If you touch a pencil to your fingertip, you'll see that it makes a big depression all around the tip of the pencil. Yet, when you don't look, you can sense that it is a point that's touching your skin, not something like an eraser. The way that your body allows you to sense that is through lateral inhibition. This is what's shown here. We've got this point touching the skin. It's mostly activating this second neuron, but it is also activating the sensory touch receptor neurons 1 and 3. Without lateral inhibition we would get this yellow curve where we have neuron 2 excited the most and 1 and 3 excited less. The way that they convey how excited they are is by action potential frequency. Since 2 is being activated a lot, it's firing action potential very rapidly, versus 1 and 3, which are firing action potentials less frequently. However, what we actually perceive after we add lateral inhibition is in this second situation, where 2 is still activated but 1 and 3 are highly inhibited. That actually changes the action potential frequency such that 2 is still firing fairly rapidly but 1 and 3 are firing much less. That's what allows us to really feel the point of the pencil and kind of ignore the depressed skin around it. That's what lets us know that it's something pointy on our finger and not something more dull. The circuitry that allows us to do that is shown here at the bottom of the slide with these yellow arrows showing the inputs coming in. We have these divergent and convergent networks happening where the red neurons are the inhibitory neurons. So you can see that each neuron is going to inhibit its neighbors. This middle neuron, neuron 2, is going to inhibit both 1 and 3. And neuron 1 is going to inhibit 2 and neuron 3 is going to inhibit neuron 2. But since 2 is being activated so much, it's going to inhibit 1 and 3 much more. That's what results in this middle graph showing action potential frequency. What has happened is the difference between the action potential frequency of neuron 2 and neurons 1 and 3 has increased. That's what allows us to feel the point. I'm not so concerned that you understand lateral inhibition and the details of it. I just want to give you a concrete example of how these networks can act to accomplish something that the nervous system requires, give you a real concrete example of this. We're going to finish up just talking about a couple of specific types of synapses. One, to give you a better sense of what's actually happening with synapses. And two, because you're going to hear about these synapses all throughout the rest of the course. They're going to be involved in controlling the organs that we're going to study. So one type are cholinergic synapses, named because in those synapses, that pre-synaptic cell is releasing acetylcholine as a neurotransmitter. On the post-synaptic cell, there are two types of receptors that can be present. One type is the nicotinic ligand gated ion channels. They're nicotinic acetylcholine receptors, which are ligand gated sodium channels. Nicotinic receptors are found on skeletal muscle and in the brain for example. THe second type are acetylcholine receptors that are muscarinic. Instead of being ligand gated ion channels, they're G-protein coupled receptors. They will bind the acetylcholine, and then start some sort of signal transduction cascade that will lead to changes in ion channels or other changes in the cells to cause an effect. The muscarinic receptors are found on the heart, smooth muscle, glands, and also in the brain. Another type of really important synapses are the adrenergic synapses, which use catecholamines. The neurotransmitters are norepinephrine and epinephrine. Epinephrine, is the same thing as adrenaline. That's why they're called adrenergic synapses. Again, we can have different types of receptors on the postsynaptic cell, alpha- or beta-adrenergic receptors. There's different types of those receptors. We'll be getting into that in different tissue and organ types, in which adrenergic receptors are expressed. Again these are G-protein coupled receptors that will act through second messenger systems. They're going to be present on our blood vessels, in the airways of our lungs, the heart, smooth muscle, and glands. They are very prevalent receptors and synapse types. So we've talked about graded potentials and how those are going to be summed throughout the neuron and how then we're going to be able to communicate using synapses between neurons. And how that transmission of information across the synapse is going to be very quick and very efficient in its effects on the postsynaptic cell.
