So the retina is made up of five basic types of cells. We've already talked some about the photoreceptors. And they're found in these sublayers of the retina from distal to proximal. There's the outer segment which is where we find the disks that contain the photo pigment. There is a layer called the outer nuclear layer which contains the cell bodies of these photo receptors. And then there is a layer of synapses called the outer plexiform layer. This is where the synaptic terminals of photoreceptors interact with two of the remaining five types of cells that we have in the retina. These synaptic terminals of photoreceptors release neurotransmitter on the endings of a type of cell called the bipolar cell. Here we have an illustration of a bipolar cell. Its cell body sits in the inner nuclear layer. And it's called bipolar because it extends processes in two directions. In the distal direction, it makes contact with the photoreceptor terminal. In the proximal direction, it makes contact with two of the remaining cell types in the retina. So in addition to the bipolar cell we also have in the outer portion of the retina a cell called the horizontal cell. And it's called a horizontal cell because it gives rise to processes that extend over some distance in the horizontal axis of the retina. The horizontal cell both receives input from the photoreceptor but also gives rise to input to the photoreceptor terminal. So there's a bidirectional relationship from the physiological perspective between the photoreceptor and the horizontal cell. Well, let's look in the inner part of the retina and encounter the two remaining cells that we find. As I mentioned, the bipolar cell sends signals that interact with these two cells. And the major cell that we find in the inner part of the retina is called the retinal ganglion cell. Now, just a word about this name. It may be confusing to you that we use the word ganglion to describe this particular cell. We're used to thinking about a ganglion as a nice ball of cells that sits outside of the central nervous system. Here, rather than having a ball of cells, what we discover is that the ganglion cells constitute a layer several cells thick across the inner surface of the retina. Well, the ganglion cells receive direct input from the bipolar cells, they also receive indirect input. From the amacrine cells, and the amacrine cells like the bot, like the horizontal cells, gives rise to horizontal connections that extend some distance across what's called the inner plexiform layer of the retina. So, I wan't you to notice that in the histology of the retina we have this alternating nuclear layer, plexiform layer, nuclear layer, plexiform layer. And then really another nuclear layer that we call the ganglion cell layer. And it's here that we find our five principle cells and their connections. Well, I'm not sure how much background noise you're hearing right now. I rather quite enjoying the sound of the rustle of the leaves and the birds, and the cawing of the, of the crows. But I'm quite irritated at the moment. Because it sounds like I hear the canned music of an ice cream truck. I don't know if you experience that phenomenon where you are but we seem to have a vehicle driving not too far away. Playing music trying to attract people to sell ice cream. Well, hopefully that vehicle is on it's way, gone and we can return to our discussion of the retina. Okay, I need to make a few additional points about these cells in the retina. Let me point out how short these distances are in the retina. The entire thickness of the human retina is not more than a millimeter or so. And, as a result, there really is no need to generate action potentials to get a signal from, let's say, the outer nuclear layer to the inner nuclear layer or from the inner nuclear layer to the ganglion cell layer. However, it's quite a different story when were talking about getting signals from the retina back into the brain. So as a result what we've discovered electrophysiological is that photoreceptors generate graded potentials. Bipolar cells generate graded potentials. But ganglion cells, they generate action potentials. And we think this makes good sense because the graded potentials are sufficent to span the shorter distance from one cell to the next within the retina. But if the ganglion cell has any hope of sending an electrical signal on its way to the brain, then action potentials are going to be needed. To traverse that distance, with fidelity and indeed that's, that's the case. So the ganglion cell is the only neuron in the retina that generates an action potential. While there is one other cell worth mentioning here, before we move on, and that is a special type of glial cell which is not illustrated here. But glial cells exist in the retina and this cell is called a muller cell. And it functions in a variety of ways to support both the metabolism and the signaling activity of the neurons of the retina. Well, now I'd like to focus in on the photoreceptors. And the phenomenon of phototransduction. As I mentioned when we began to consider our sensory systems, the challenge of phototransduction is one that needs to be explained and accounted for in each of our sensory systems. And for vision, just speaking for myself. I always considered this such a deep mystery. I remember as a child just wondering how could it possibly be that we can see? How is it that this energy that we now understand to, to come in the form of, of particles in, in waves of light. How can that energy turn itself into signals in our brains that give rise to perceptions? Well this is really a profound question, and we don't know the full answer yet. But we've gain considerable insight In the last several decades, about how the process of phototransduction works, and it works in the photoreceptor. So let's turn our attention to these photoreceptors. What we find is that fundamentally we have two types of photoreceptors in the retina. There is a type of cell called the rod and the ride is so named because of its long cylindrical outer site. And there is a cell type called the cone and rather than having a rod shaped outer segment it has a sort of conical shaped outer segment. Well there are multiple differences that we want to discuss concerning these two cells, and we'll get to that shortly. But first I want to focus in on the issue of phototransduction, which we know best for the outer segments of the rod. And first let's consider what happens in the outer segment of the cell when it's kept in the dark. And the surprising feature of this photoreceptor in the dark is that it's actually depolarized, at least relative to other neurons that we've talked about so far in this course. And this depolarization is supported by something that we call the dark current. In the plasma membrane of the outer segment of our photoreceptors, we have an ion channel that is permeable to calcium and sodium. This channel is gated by the second messenger, cyclic GMP. So when cyclic GMP is present in abundance, it interacts with the cytoplasmic phase of the channel. This allows calcium and sodium to diffuse down their concentration gradients and enter that postsynaptic cell. Well, this helps to support a depolarized resting membrane in these cells. There are other Ion channels in the photo receptor that allow for the eflux of potassium. Well, when a cell is in the dark the influx of calcium and sodium contributes significantly to the resting membrane potentials. So for this type of cell, we have to consider these additional ions if we're going to predict the resting membrane potential. Unlike our simple neurons and axons that we considered earlier in the course where a leak for potassium was sufficient to approximate the resting membrane state. Here we have to also consider these additional active conductances for calcium and for sodium. Now, the process of phototransduction requires the interaction of a photon of light with a photo pigment. And the photo pigment is a complex molecule which consists of a opsin, which is a large protein structure that interacts with a smaller organic molecule called 11-cis retinal. Now this opsin, is actually going to be familiar to you, because it is a member of this seven trans-membrane protein family that we've encountered previously in this course. We've encountered this general structure previously, the seven transmembrane structure. Is exactly what we saw when we considered metabotropic receptors for neurotransmitters on postsynaptic terminals. In fact, the opsins are part of that same family of proteins. Quite remarkable, don't you think, that a metabotropic structure Is present both in postsynaptic membranes within the brain. And as a key component of the photo pigment in the eye. Well let me tell you about the role of these two components. So the 11-cis retinal is the organic molecule that will interact with the photon of light directly. The opsin that surrounds that 11-cis retinal, fine tunes the response profile of that 11-cis retinal. So we actually have four kinds of pigments in our photo receptors. And rods, we have the rod opsin. And it has a particular spectral sensitivity which is plotted in this, chart of relative spectral absorbance versus wavelength of light by this dashed line here. And you can see it is somewhere near the middle among our family of opsin proteins. Cones contain one of three different opsins and those opsins allow for the fine tuning of the responses of the 11-cis retinal to wither shorter wavelengths of light, medium wavelengths of light, or longer wavelengths of light and obviously the medium and long Are a much closer in their spectral sensitivity than they are to the short. So these three different opsin proteins that are found within the cones provide the foundation for color vision. We'll say a little bit more about color vision as we move on in our studies of vision. Well, let's see what happens when light interacts with this photo-pigment. Here we have a recording of membrane potential from a photreceptor, and the experiment is to provide a very brief flash of light. And what we can find is that there is a graded response with the intensity of that flash of light. But notice the polarity of the response. Again, the resting membrane in the photoreceptor is around minus 40 millivolts and the response to light striking the outer segment of the photoreceptor Is hyperpolarization. And with increasing intensity of light we see a deeper htyperpolarization perhaps down to about minus 65 millivolts. Okay, well how does this work? Well, when light strikes the outer segments of the photo receptor There is a seriers of molecular events that lead to a reduction in the concentration of cyclic GMP. So when the level of cyclic GMP is reduced, then these channels close. And the closure of the cyclic GMP gated channels means that calcium and sodium... Can no longer enter this cell and support its depolarized state. Rather, the potassium channels remain open, allowing for the efflux of potassium, and that brings that membrane down to a more hyperpolarized state. And that allows the membrane to hyperpolarize to a predictable equilibrium, near about minus 65 millivolts for many photoreceptors.
