All right, we have right now finished topic about phototransduction and photosignaling in the photoreceptor. And this photoreceptor signal then needs to propagate or process by the the retinal neural secretary. So, for the retinal neural secretary, of course they all the retinal interaction origin. Actually, this gentleman make a huge contribution in 1967, because he work in the on the Retinal Physiology origin. He got a Noble Prize. So, when they recall from the Retinal Ganglion cell, so in the photoreceptor, people used suction pipette recording. And then in the ganglion cell, then people typically used the other recording method. You can maybe just put a sharp electrode. [FOREIGN] You can detect the spikes, these extracellular recording. Or you can use the patch clamp recording from the single cell. It doesn't matter which kind of recording, but when you record from a ganglion cell, you give a light stimulation. Here, it's different. The ganglion cell will give the action potential firing. [FOREIGN] Action potential [FOREIGN] spike. So, when you have this one, this is actually, we saw in the dark without any stimulation. Interestingly, the therapy was spontaneous action potential. But the retinal is quite low. But when you give a light spot. [FOREIGN] Quite strange here. If you give a larger, the light spot stimulation, the response gets smaller. [FOREIGN] And then interestingly, if you do a ring of the life simulation, the center is still black. [FOREIGN] The ganglion cell here actually inhibited, no any response. But actually, this spontaneous also disappear. [FOREIGN] Now, this actually, if you define, actually, in the center, then this one, in the center, this spot actually is the excitation. And then in this region, around the region, there is an inhibition. So, we talked about the receptor field, right? It doesn't matter excitation or inhibition, those all are the receptor field. So, for this retinal ganglion cell, the receptive field covers this region but has two separate regions. In the center, there is excitation in the surrounding inhibition. This is called center surround receptor field. [FOREIGN] A lot of computation came based on this [FOREIGN]. Of course, actually, you can record from another cell. Maybe just has that opposite receptor field that it means actually in the same term, then you give it a supporter here inhibition. But it will give you the surround like stimulation. Surrounding, then you have the excitation. Okay, this is what we call, this is the on center, on center offs around, this is called off center, offs around, [FOREIGN] digit off. Yeah? >> Receptor of this experiment. Retinal stimulates the ganglion cell through the concept. And then this goes to the ganglion cell. >> What's your own answer? >> My answer [INAUDIBLE] >> Yes, only. Detect light, right? Photoreceptor detect the light. >> So, the [INAUDIBLE] of the [INAUDIBLE] >> In the? >> [INAUDIBLE] >> Yes, yes. Is it just aware in the rat. You shine the light, spot actually. It doesn't matter, you sign the light from the ganglion cell side or the photoreceptor side because it's transparent the retina. So, the hollow region of the retina covered by this light, then that's the receptor field, okay? >> [INAUDIBLE] Cell [INAUDIBLE] >> These two? >> Yeah. >> So, you just recalled from this cell, okay? You called it from one cell. And then, you give it the light stimulation, and you need actually move around as a light stimulation. Sometimes, you cannot get any response because it is out of the receptor field. And then when you move one region you see the excitation. And you increase the light. And then you see inhibition. And then you define this area is the receptor field. And for another cell, of course, you do the same thing. Maybe it's a different region to receptor field. >> So, before you do the experiment, you have to distinguish which retina cell? Or [INAUDIBLE]. >> You don't need. You don't need. >> Do you have to to do the past stimulation- >> Stimulation, you just you just arrange them. >> [INAUDIBLE] >> Your screen, your screen. Yeah, you came up with this slight spot. For example, you have this huge rectangle piece, like this size, okay? This size, and then you move the spot. The stimulation around this whole area. You record from the beginning of the sale. You see a response, and you know there is a effective receptor field there, right? >> [INAUDIBLE] >> Yep. Okay, so let's look here. It's quite interesting, right? So, we know, actually, in the photoreceptor here, the response is as it is, is hyperpolarization and no spiking, okay? But actually, if we recall from the ganglion cell, then you have the spiking firing. And also, you have excitation, and also have inhibition corresponding the excitation is depolarization, inhibition is for hyper polarization. But in this the input of the signal here is only hyper polarization [FOREIGN]. Right? That means there's a lot of processing happening inside here. Okay. So, let's take a look, actually, what actually happened at this synaptic region from the photoreceptor to the bipolar cell. Let's take a look at the process here. Actually, the first one, I want to show you is a picture of this one. This is a from a new paper, 2015, Annual Review of Neuroscience. So, this is actually a cartoon to show the retinal connection. This is the photoreceptor. This horizontal cell. This is a bipolar cell. And the bipolar cell, actually, look at it here. This one is short. This one is actually quite long. These actually are two types of bipolar cell. This one is called off. Because actually, if you give a light to this bipolar cell, this bipolar cell actually is a hyperpolarization. But then if you give a light to this bipolar cell, this bipolar cell will give depolarization. Things owned by polo as they are. If they just by this anatomy, they what you can recognize this, this, bipolar cell, the danger area is quite close to the photoreceptor layer. This is called off, but this one, the axon terminal is closed to the ganglion cell layer. This is called on, okay? So, there are simultaneous, actually, pathways, on and off. And in the photoreceptor, just off, right? Because they have polarization. But here, became two layers. Let's look at what happened. So, you see this is the short one, by polar cell this is off by polar cell. This is owned by polar cell, a long door one. So, and I guess you want to talk about this in your train meter, right? In these lectures, so how it happens, the same input here is hyperpolarization. But then, these two cells, [FOREIGN] how can you achieve this one? Two different cells, okay? That's one way to achieve, but it's quite a challenge. But here, if you see one to here to specific another one to here. There's a huge demand for the cell. So, you need to find a specific release. We know right now, okay? This cell radiates the same neurotransmitter rudiment. >> Give a different receptor from your [INAUDIBLE]. >> Okay, good. So, then you can achieve, actually, express, your transmitter receptor on the bipolar cell. Why? Actually, we know right now, okay? This whole bipolar cell that express the emperor receptor. AMPA receptor is the most abundant receptor in the brain, okay? [FOREIGN] AMPA receptor, A-M-P-A. And this one, bipolar cell, they use a mglurs6. Metabotropic glutamate receptor type six. [FOREIGN] Now, because the empire receptor is always, actually, you have a glutamate binding. The receptor then will open and then the cell depolarize. So, in the dark, this cone cell is depolarizing. Because it is that TCP open the CNG channel, then the cell depolarized. And then depolarization make a lot of glutamate release, okay? So in the dark, glutamate release to this bipolar, then depolarize, then you have a light coming. This cell has polarized, and the release reduced. And then this cell will hyperpolarized, right? But [FOREIGN] they opted. Because this receptor is really different. You need to couple to a G protein, mGluR6, and then when you have glutamate released in the duct, the glutamate binds to the mGluR6. And then this mGluR6 acting with a G protein, then somehow, through a cascade. To close a channel, of the TRP channel, T-R-P channel, in the membrane. Then the cell have polarized, but when you have a light coming, less glutamate release. And then, this hyper, the channel, TRP channel, T-R-P channel, will be open again because it's a receptor. Activation, actually, now it should be less activation with mGluR6, and the TIP channel, TIP channel open. Still depolarize. [FOREIGN] Yeah. This is actually a cycle. Y is actually from the same cell, cone cell go to a empire receptor. And then go to off bipolar cell to [INAUDIBLE] and receptor. And then through the gene protein. And with this channel, we know right now is TRP channel, T-R-P, TRP channel, okay? Identified. We know right now, okay, so the ganglion cell has the same surround the receptor field, right? So, using this, we can actually look at this computation in the retina. So, how the center-surround cell receptive field achieve? This is, okay, let's take a look for this one, this is the photoreceptor. And then, you have a bipolar cell here. This bipolar cell is an off bipolar cell or hyperpolarizing or H bipolar cell, okay? And then, if you have a light coming, this cell, hyperpolarized. This cell also hyperpolarized. Because these cell express empire receptor, right? Okay, this is the center response. How does the surrounding? The surrounding actually, right now, this is quite important, okay? So, you see this dendrite actually of the bipolar cell does not connect to the other photoreceptor. But actually, this region still considers the receptor field of this cell. Because there is another cell, horizontal cell, connect all these cells. A horizontal cell receives the input from this cell, but also, at the same time, this horizontal cell will feed back to each of these cells. Okay? So, let's take a look. This horizontal cell receives the input from these cells. And then we have a neck to feed it back to the inhibitor. Feed from the neurons. And this inhibition, from this cell, it also depends on the depolarization. So, if the cell has depolarized the feedback, then it's less. So, when you have a light only active in this region, what will happen? I will give you a clue. This is the horizontal express empire receptor. Hyperpolarization here, this also is hyperpolarization, right? And feedback, then let's feed it back. Feedback is actually the best thing here, it reduce in your transmitter, and then in this case, the neurotransmitter will find this cell, will have more neurotransmitter release, right? More neurotransmitter released will cause. This is empire receptor expressing in cell, then, be polarized. So, you kind of, you say summary the [FOREIGN] okay, we can explain in next lectures. Take a financial [FOREIGN] concept [FOREIGN] receptor field knowledge system. [FOREIGN] Computation. Same thing with [FOREIGN].
