The Science of Everything Podcast - Episode 45: Vision Part 1

Episode Date: March 10, 2013

We commence our grand journey to understand the visual system by examining the eye, its anatomical structure and physiological properties. I discuss image formation in the eye, including an explanation of the role of the lens, iris, and cornea. I also explain the phototransduction, the fascinating molecular process by which photons falling on the retina are converted into neural signals that the brain can interpret. Recommended prelistening: Episode 18 - Biochemistry Basics, Episode 25 - Tissues, Organs and Systems, Episode 32 - Light and Optics, Episode 38 - Neurons and Synapses.

You're listening to The Science of Everything podcast, episode 45, vision. And I'm your host, James Fodor. In this episode, we're going to look at human vision, going right from the eye through to the computational analysis of visual input in the brain. So this episode is... The content that I have for this episode is going to be far more than I can fit into a single podcast. So I'm thinking this is going to go over two, possibly even three episodes, depending on how we go.

So I don't know exactly how much we'll get through in this episode. first episode, but we'll get as far as we can. So what I'll do is I'll give an overview of everything that I plan to discuss over the series of episodes, and then we'll get as far as we go in this one, and pick up where we left off in the next one. So first, I'm going to talk about the eye, the anatomy of the eye, how images are formed, the visual field, and after that we're going to move on to talking about the retina, which, I mean, is part of the eye, but it's where the actual rods and cones that do the actual transduction of light into neural inputs that the brain actually understand. So it's kind of the crucial part of the eye, so we'll sort of consider it

separately, or in its own section. We'll look at rhodopsin, how phototransduction occurs, the bipolar cells, ganglion cells, and some of the other cells that are found in the retina. Then we'll look at the output of the retina from the optic nerve leading through the optic chasm and into the lateral geniculate nucleus, which is the first region of the brain that the visual input goes to. After that, we'll talk about the primary visual cortex, or V1, the different layers within V1 and cell types, ocular dominance columns, orientation columns, and some other interesting things that occur there. After that, we'll look at some of the higher levels of processing that occur in various other regions of the brain, including V2 and V3,

the MT and MST regions, V4, which has a lot to do with colour, the inferior temporal cortex, interparietal sulcus, and some other regions that are of relevance. And finally, we'll conclude with a look at sort of the more abstract computational analysis that the brain does, specifically how it takes the inputs that it receives from the retina and transforms those into visual perceptions and how it recognizes objects and detects motion and depth and things like that. So at the outset, I think it's important to say that many of the issues that I'm going to discuss are still not completely understood.

In fact, many of them are very poorly understood, especially the further I go on. I mean, the stuff I talk about about the anatomy of the eye and the retina and so on, that's pretty well established. the structure of the visual cortex and the lateral geniculate nucleus, that's pretty well known, although there are still a lot of questions there. Higher-level processing and computational analysis is still quite poorly understood, and all we've got largely at the moment are sort of plausible hypotheses in various competing theories, backed up by a certain amount of computational or anatomical evidence,

but we'll get to that. So just be warned that it gets murkier the further we progress through the brain and the processing cycle. In terms of recommended pre-listening for this episode, or a series of episodes, we're going to cover a lot of ground. So many of the episodes that I've talked about, where I've talked previously about issues of biology and light or cells, will all be relevant. In particular, I strongly recommend episode 10 on the cell, episode 18, biochemistry basics, and episode 38 neurons and synapses. Episode 38 in particular is essentially vital, because I'm not going to go into detail about what neurons are and so on. I'm going to assume that you have a background in that. Episode 32, light and optics will also be somewhat useful for the first part about the eye and image formation.

Okay, so, without any further ado, let's get into it. So, first of all, I'm going to present a very gross-level overview of image processing and the overall schema of how visual information is first detected and then processed by various parts of the brain. So I like to divide this into about four main categories. Well, I suppose five main, four or five main categories. First of all is the eye. So this is literally the eyeball itself and the lens and cornea and all that sort of stuff. That's where the light first enters essentially the body and is first formed into an image.

But in the eye itself, no visual processing occurs. It just forms an image. The second stage is the retina. Now, the retina is actually part of the eye, but I think it's useful to separate it. The retina includes the rods and cones that actually detect light and convert it into neuronal signals that the brain can understand. There's some interesting biochemistry and elements we'll look at there in terms of how that occurs.

The third level is the initial processing, or the very first processing of visual information in the brain. This includes the transmission of the visual information from the retina into the brain via the optic nerve and the optic chasm and into its first sort of processing location in the brain, which is called the lateral genucleiculate nucleus or LGN, and we'll talk more about that later. So that whole bringing the information into the brain and getting to the brain and getting to the LGN, that's level 3, or stage 3.

Stage 4 is processing in the primary visual cortex, or V1, where the information is taken after it goes to the LGM. And finally, higher level processing in cortical areas, which are basically cortical areas which perform high-level processing after the information has already been taken to V1. So I'm presenting this as kind of a linear process where, you know, the light comes in, the eye, it's detected by the retinaer, it's passed into the brain, goes to the LGN, goes to V1, then goes to the higher levels. It's not quite that simple because there are, especially from the V1 to the LGN

and from higher level areas back to V1, there are sort of backward-directed projections of axons that go forward, like from V1 to V2, for example, and then projections go back from V2 to V1, or forward projections from the LGN to V1, and backward projections from V1 back to the LGN. So it's not quite so simple and linear as I'm presenting it, but sort of a first-level analysis, I think that's a useful way to think about it.

So just to recap, the eye, light comes in the eye, is transferred into, it's transferred into electrical signals by the retina, is moved into the brain via the optic nerve and optic chyasm, and is first processed by the lateral genucle nucleus. Then it is transferred to the primary visual cortex, which is called V1, and finally, after that, it's progressively processed or moved along to higher cortical areas like V2 and V4 and so on, which we'll talk about later. So keep those five basic categories in mind as we're moving through this, series of episodes. But we need to start at the beginning, which is a good place to start,

and we'll talk about the anatomy of the eye. So the adult human eye is only about 2.5 centimeters in diameter, which is actually quite small, if you consider how important it is, because vision is obviously the primary sense that humans rely on to interact with the world. So given how important it is quite small. The eye is kind of like an onion, really. It has a bunch of layers, and you strip out the first layer, and then you can look at the second layer, and then you can move further and further in as you peel out the layers. But we'll start from the outside and work our way in. I mean, the eye is roughly spherical.

It's not completely spherical, although it does have a sort of a dimple that comes out the front. So it's like a, imagine it as a sphere with a sort of a hemispherical protrusion poking out the front. If you sort of close your eyes and touch your eyelid, you'll sort of feel that, sort of bump in the front of your eye. That bump there is called the cornea, and that's where we're going to start. The cornea is at the very front of the eye. It's made up of several layers of transparent, connective, and epithelial tissue. If you're not sure what I mean by that, check out episode 25 on tissues, organs, and systems. But these tissues are transparent, which is important, obviously,

because if the light couldn't pass through the cornea, then we wouldn't be able to see anything. The cornea is curved, which assists in the focusing of light. And this is important to understand how an image is formed, and I'll get to that in a moment. So just remember that the cornea is curved, and that means it can help in image formation. Exactly how it does that, we'll come back to. So behind the cornea is a sort of a roughly hemispherical shape called the anterior chamber, which basically just means like the chamber in front. And it's filled with transparent fluid called aqueous humor.

Now, this is a little interesting thing here. Aqueous humor is really quite a stupid name, in my opinion, because it's basically just Latin for water fluid, aqueous meaning water, and humor just means like bodily fluid or just fluid generally. So, I mean, it's not a very descriptive name, but I guess it suits the purpose. Basically, all this fluid does is help to maintain the structure of the eye and also helps to provide nutrients for the cornea, sitting in front and the lens which sits behind.

There's another type of watery fluid that's in the eye, which is called the vitreous humor. So don't get those two confused. We'll talk about vitreous humor a little bit later, but the aqueous humor is at the front, just behind the cornea, and the vitreous humor sits back further into the eye, and we'll talk about later.

Now, just behind the aqueous humor, or the anterior chamber, which contains the aqueous humor, is the lens, which is also transparent. It's a bi-convex structure, which essentially means that it's sort of like... So convex means it basically pokes outwards, you know, like someone's belly. It pokes outwards. It pokes outwards like that on both sides. So that's what b-convex means.

And again, that shape is crucial because it means it can help focus the light to form an image. And we talked a bit about this on the episode on, what was it, 32 on light and optics. And I'll talk more about that in a moment when we cover image formation. But again, the shape of the lens is crucial for image formation, and the fact that it's transparent is also crucial because otherwise the light wouldn't be able to pass through it. The lens is quite elastic, although it's still fairly firm, but elastic. It's mostly made of transparent proteins called crystalline. It's actually pretty cool, given that they're sort of fairly strong, but also completely transparent. The lens is kept in

position by what's called the ciliary body, which is comprised of ciliary muscles and ciliary processes. We won't go into the details of what those are, but basically that there's muscles and tendons which connect to the lens, help it to keep it in position, and also are able to pull on the lens in order to alter the shape of the lens. And altering the shape of the lens is crucial, as we'll talk about in a moment in the image formation, because in order to focus on light coming from different distances away, it's necessary to change the shape of the lens. So these ciliary muscles and ciliary processes help with changing the shape of the lens.

Just sitting in front of the lens is the iris. The iris is the coloured part of the eye. Eye color just refers to the color of the iris. It's a circular structure which essentially sort of surrounds the lens. it's responsible for controlling the diameter and size of the pupil, well, the pupils, but the pupil in one eye. The pupil is essentially just the hole, really, or the space, inside the middle of the iris. So if you look at someone's eye, there's the white of the eye, which is the sclero.

We'll get to that. Then you'll see a coloured sort of circular disk, which is the iris that has a colour. And inside that, you'll see a dark circle, which is called the pupil. Really the only purpose of the iris is to change in size, either get bigger or get smaller, such that the size of the pupil changes. And basically, this is done so that we can see in both light environments and in dark environments. In dark environments, you need more light in order to sort of see, and so therefore the pupil needs to increase in size, to dilate, in order to let more light in. And so basically the iris is made of a bunch of muscles,

which can contract or relax in order to change the size of the iris, and therefore change the size of the pupil. The people is dark, basically, because what you're seeing there is not a any particular structure. The iris is a structure which is located just behind basically the cornea, and the cornea is transparent, so you can't see it, but if you see light reflected off the front of someone's eyes, you're probably seeing it reflected off the cornea.

But inside the pupil, you're not really seeing anything. What you're seeing is basically the retina, which is way back. You're seeing the back of the eyeball, basically, but you can't really see it because it's, I mean, there's not very much light gets out of there. Basically, the light goes into the eyeball and then scatters around, and much of it's

absorbed by the various pigments in there, so not much if it comes out again. However, if you flash a very bright light in there, in someone's eye, then you'll see the back of the retina, and you'll see blood vessels, and it looks a bit red because of the blood that's there. Essentially, this is the cause of the red eye phenomenon in flash photography, when people's eyes go red. It's because, basically, the light is reflecting off of the blood vessels and some of the other things on the retina, and coming, it's reflected back through the pupil, and then you can see it. You can't normally see that because the light's not bright enough. Okay, so that's the iris, that's the

the pupil, that's the cornea. Just located behind the lens, which remember is behind the iris, which in turn is behind the cornea, is basically the cavity that contains the majority of the volume of the eye. In this cavity is located. This cavity contains, as I mentioned before, vitreous humor. And this is a watery substance. I mean, it's a solution. It's got like various proteins and stuff in it. It's mostly water. They're like 99% water by volume. It contains very few cells. And like vittria, sorry, like aqueous humor, its purpose is pretty much just to maintain the structure of the eye. But this vitrious humor is, comprises the overwhelming majority of the internal volume of the eye. The stuff that I talked about before with the

cornea and the acqueous humor, the, and the lens, and the iris. That's all up the front in a relatively small area, you know, that protrudes out the front. Most of the volume of the eye is taken up by the vitrious humor. One final thing that I need to talk about, which I mentioned before, is the sclera, which is the white of the eye. Now, this is opaque, which is why you can see it, why it's white. It's not transparent like the lens and the various fluids are. Basically, it's made of elastic collagen fibres, again, why you can't, which is why you can't see through it. It's a protective outer layer of the eye. So basically, you know, the eye is more or less spherical. The outer surface of the eye is covered by this protective elastic tissue, which is called

the sclera, and it looks white. Now, you can see the sclera in the white of the white. You can see the of the eye, sort of surrounding the iris. That same material actually surrounds all of the eye, like going around right to the back and the sides and someone, you obviously just can't see that because it's covered by the eyelid and so forth. If you pull the eye out of someone's socket, though, you would see that. There's essentially an opening in the sclera, or a region of the front of the eye that the sclera doesn't cover, and that's where the cornea pokes out, and where the light goes in. If the sclera completely covered the eye, then obviously no light would be able to get in. Essentially, the eye is just like a big ball covered by the sclerer. At the very

front of it, you've got the cornea which sort of pokes out a bit, and the cornea itself is transparent. Behind that, you've got the lens and the iris changing size to let various amounts of lights in, and the light actually travels through the lens, through the pupil, and then travels through the transparent vitreous humour in the main interior volume of the eye. Okay, so that's enough on the anatomy of the eye. Now let's talk a little bit about image formation, so how does this bunch of tissue actually form an image? So, recall from the optics episode that we did, that light or stuff that we see is just electromagnetic radiation, so it's just essentially fluctuations in electromagnetic fields.

That's essentially what it is. Somehow the eye has to detect this and transform it into neural signals, action potentials, which is really all the brain can directly understand. It does this via the ros and cones located in the retina, which is at the back of the eye, and we'll get to that in a moment. But at a broader level, how does the eye form an image? Because if the eye did not somehow form an image, you could potentially still detect light and colors and so on,

but it would just be all a blurred jumble. Like if you set up a projector, but don't focus it properly, you can still see stuff there, but it's just blurry nonsense. You have to form a clear image in order to be able to sort of see anything of interest. The lens on the cornea are the main parts of the eye that are responsible for doing that. Their task is essentially to focus the light that comes in in such a way that it forms a clear image on the retina, and then the retina gets to actually processing that image

and turning it into neural signals. But how does that image formation actually occur? Well, remember refraction from earlier episodes we've done? This is when a wave changes its direction as a result of a change in the speed with which that wave travels. Now, light travels always at the same speed in a vacuum. However, light does not always travel at the same speed in different materials. So, in particular, light travels through the cornea and through the lens,

and through the aqueous and vitreous humors at different speeds, then it travels through air. And so as it travels through these tissues, it is bent. Well, the humors aren't really tissues, but those substances, the light is bent. That's called refraction. Now, in particular, most of the bending occurs at the cornea and the lens. So I'll talk mostly about those.

Remember I described the lens as a bi-convex structure? This means that it sort of pokes out in both directions. Not like a sphere. It's sort of like a pointed sphere or like a football shape, standing upright, something like that. Hopefully you can visualize what I'm talking about. A magnifying glass has the same basic shape. Essentially more rounded or more poking out or more curved the lens is,

the more bi-convex it is basically, as opposed to more flat. But the more rounded it is, the more it will bend light, and therefore the greater its refractive power is the word we use. The greater the power of the lens. And the closer the image will be, the closer the image formed by the lens will be to the actual lens. So the way image formation works is that you will have light, coming to you, let's say coming to the lens,

from all different places in the visual field. The visual field is just the region you can see from the eye, or from both your eyes. In order for an image to be formed, what you have to do is focus the light or arrange it such that all of the light from one location in the visual field ends up at a single

location on the retina, or more generally just at a single location where you're forming the image. Now that might sort of sound trivial, but generally that won't be the case. Generally, like, for example, if you just look at the walls, the walls look white. even though all of the light from, say, the room that you're sitting in, is being reflected from those walls, like all of the lights there,

but you don't get an image because light from the lamp, light from the computer, light from the bed, light from the desk, light from whatever, are all hitting all parts of the wall. And so what you see is just a jumbled mess, which you just interpret it as like a color or whatever. You don't see an actual image. In order to get an image, you need it to be so that the light from one particular key on your keyboard falls on one particular part of the wall,

and then a light from the next screen in your keyboard falls on the part of the wall just next to that and so on. So basically you get a clear one-to-one mapping of light from the stuff in the real world to light to wherever you're forming the image. In case of the retina, what you need to have is light from a particular point in the visual field needs to all converge to a single point on the retina. If there was no lens in the eye and no cornea, then that wouldn't happen. So you would just be able to detect color and light basically, light and dark. You wouldn't be able to see an image. In order for an image to form, you need to have a lens. But more specific than that, the lens has to ensure that it focuses the light so that you get one object in the real world being focused at one point on the retina.

That has to occur. So the focusing has to occur so that the image occurs right on the retina. It won't do if the image is formed just in front of the retina or just behind the retina, because then at the retina itself, the image will be blurry. And this is essentially like if you have a projector and you just, you know, there's often like a knob or something like that where you change the focal length of the lens or whatever that's controlling it. If you turn it a bit one way, then it gets blurry because the image is formed in front of the wall, and so you can't see it properly. And then if you turn it the other way, it also gets blurry because the image is now being formed behind the wall,

and so is blur again. You need to have it just right. And the lens is basically pulled into just the right shape by the various muscles and ligaments in the ciliary body surrounding it. The lens is pulled into just the right shape so that whatever object you're viewing, you can focus that light and have the image appear right on the retina. people who have various types of defects with their lens basically the two most common ones are myopia and hyperopia or short-sightedness

and long-sightedness. Basically, their lens is incapable of changing shape properly so that in myopia, I think, if I'm getting it right, the image forms in front of the retina and in hyperopia it forms behind the retina, or I may have got that the wrong way around. The details don't matter too much for this episode. The point is you have to,

the lens has to form the image right on the retina. And if you focus the light too much or too little, and if the lens can't be exactly the right shape, it won't form on the retina and you get a blurry image. And sort of we wear glasses or contact lenses to basically provide extra or to alter the way that the light is refracted by the lens and therefore sort of offset that. I mentioned that the cornea refracts light as well. The cornea, however, has a fixed refractive power. It can't change shape or composition. So whenever we want to change what we're looking at or change the viewing distance of our eyes, that's all done by the lens.

So it's crucial that we have at least one refractive body that's able to change its shape. If they were both fixed like the cornea, we'd essentially only be able to view objects clearly at a fixed distance. You know, 10 meters away, everything would be clear, but everything closer than that and further away than that would be blurry. And this is essentially what happens, especially to older people, because their lenses tend to become stifferent, so they're more brittle and it's harder for them to reshape. So they can see things clearly if it's just the right distance. Closer than that, they can't focus properly further away that they can't focus properly. Okay, so that's how image formation occurs.

Image formation is just about getting an image on the retina. It doesn't say anything about how that image is actually interpreted by the brain or how it's actually even transferred to the brain. So far, we haven't said anything about the brain. We've just said something about how the light comes into the eye and we get an image from that. Now we've got to figure out a way of capturing that image and transforming it into electrical neural signals that the brain can later interpret.

Just before we get there, there's a few extra concepts that I want to cover. The first is the visual field. I mentioned this before. The visual field is simply the area in space. well, in front of us, that we perceive when the eyes are fixed at a static position looking straight ahead. So if you move your eyes from side to side, you can see additional or up and down. You can see additional things. You can see areas that you couldn't see if you just were looking straight ahead. But that doesn't count as the visual field. The visual field is just,

I stand straight ahead, what can I see? The degree of resolution varies a lot in different parts of the visual field. So at peripheral vision, you know, to the side and up and down, the resolution is fairly low. It's hard to see things there. We only have really good resolution for a very small region, actually, at the very center of our visual field. But the visual field is everything you can see. So if you hold your hand in front of you and then move it to the right, but make sure you keep your gaze fixed straight ahead, so don't follow your hand with the eye.

Just look straight ahead and then move your eye to the right. You'll see you can still see your hand, but it gets blurrier and blurrier. It's sort of harder to make out. And eventually, if you can move your arm around far enough, you won't be able to see your hand anymore. That's because it's moved out of your visual field. The human visual field is roughly 180 degrees forward. But basically, if you imagine a circle sort of projecting out with you at the center,

you can see the full 180 degrees of that circle, obviously forwards from your perspective. The 180 degrees behind that, you can't see. So that's actually quite impressive in the sense that we can see fully half of a 360-degree field. This is why on computer games, for example, it's often more difficult to have awareness of your surroundings because you can generally only see something like 60 or 90 degrees,

which is a much more narrow vision, or you'll get this if you have to wear like a helmet or something that restrict your peripheral vision. It's very annoying because we're used to this very wide field of vision. Up and down, it's something like 60 degrees up and down, so a total of 180, sorry, 120 degrees up and down. So we can see quite a large area, actually, just without even moving our eyes or head.

The majority of the visual field is shared by both eyes, that is both of your eyes see that region. roughly 120 of the 180 degrees from side to side. However, the remaining information is only detected by a single eye. You can easily tell this if you just observe your visual field with both eyes and then close one eye and see what you lose. See what you can no longer observe. What you can no longer see was the part of the visual field that was only visible to one eye,

and then if you close the other eye, you'll lose the part of the visual field that was only visible to that eye. And if you subtract out those two parts, the part that was visible just to the left eye and the part that was just visible to the right eye, you'll be left with the part of the visual field that was visible to both eyes. This is called the binocular visual field, both eyes, monocular visual field, just one eye. And all this stuff about the visual field will become important later on

when we talk about how information is, how visual information is processed in V1 and so on, and we talk about retin topic mapping, which is very interesting. Final concept that we want to talk about that I want to cover is the fovea. Now, the phobia is a region of the retina. So I guess it's slightly dodgedy I'm talking about this now, because I haven't actually really discussed the retina yet, but it relates to visual acuity and visual field that I was talking about,

so I just want to cover it here. Visual acuity is just like what we can see and how accurately we can see at the resolution and so on. Visual acuity is greatest for a particular region of our visual field, and that region of the visual field corresponds to the light that falls on the particular part of the retina. The retina is just basically like all of the area on the back of the eyeball, so you know how the eyeball's just like a sphere. on the outer side, outer layer, it's covered by the opaque sclera, while on the inner layer, it's covered by what's called the retina,

which is where the photoreceptor cells are actually located. There's a particular region on this retina, which is only like one millimeter wide, so it's very small, that has a particularly high resolution, and this is called the phobia. So when you are reading, basically what you're doing is constantly shifting your gaze from one word to the next or from a small group of words to another, and you're doing that so as to direct the light onto your, phobia or, you know, phobia in both eyes, you can't read unless the light is falling on

your phobia, or maybe just very close to the phobia. You try staring at a word and then reading a word even like two, maybe three or four lines down or, you know, like ten words across or something like that. You can't do it. You can see the words there, but you can't read it because it's too blurry. You'll find you'll have to move your eyes down to that word. This shows us that the fovea is very small, only a very small portion of the visual field has sufficiently high resolution to allow us to read. And so what we generally do is constantly shift our gaze when we're looking, not just when we're reading, but when we're looking at anything, we look at, we're constantly moving our eyes around so that we can get the light from different parts of

the object to fall on the phobia and therefore see it in high resolution. There's no intrinsic reason why the human visual field, if we had enough eyes or cameras or whatever, could not cover the full 360 degrees and could not cover that with the high degree of resolution and acuity that we have from the phobia. So you could imagine how accurately we'll be able to see if we could see 360 degrees with phobia level resolution. It's hard to imagine, but if you think about it, that there's no reason why, you know, a visual field stops over here. Well, why couldn't just extend back a bit further and why couldn't it have high resolution? Obviously, with our brains, we wouldn't be out of process all that information, but I think it's an interesting

thing to think about. The fovee is fascinating, because it only comprises 1% of the total area of the retina, but it takes up over 50% of the visual cortex in the brain, which is where this information is processed. So 1% of the input takes up 50% of the processing, and that's essentially just because of the huge quantity, the huge resolution, the very high resolution that that region has. Okay, so that's the visual field and phobia covered, and that concludes our discussion of the first of our five elements of vision, the eye, and talking about image formation and the anatomy and so on. Now we're moving on to our second element, which is technically still part of the eye, but I'm going to talk about it separately, the retina. Now, I've already, I mean,

I've already said what the retina is. It's just a layer of light sensitive tissue that lines the inner surface of the eye. The retina contains the photoreceptor cells that actually transduce incident photons into electrical signals. Transduced just basically means like transform. Incident just means the photons are falling onto, like that they're literally the photoreceptor cells on the retina. So incident photons, they come through the cornea and refracted a bit, then they travel through the lens and are refracted some more. An image forms on the retina and the incident photons that are falling onto the retina need to be converted to electrical signals which the brain can then process. The retina is what does this job of transducing the photons into electrical signals. Okay, so,

So I keep talking about these photoreceptor cells. These are the cells that actually do the transducing. They take a photon, basically, and use that information to produce electrical signals that the brain can understand. How do they do that? This is one of the, I think, really cool parts of vision understanding how we go from photons, like fluctuations in the electromagnetic field into electrical signals in the brain, action potentials. How does that happen? Well, it happens, the first part of that happening is essentially in the rods and the cones.

Rods and cones, what am I talking about? There are two fundamental types of photoreceptor cells. A photoreceptor is just a generic name for any cell that does this job of transducing the photon signal. But there are two basic types of them in the human eye, and they're called basically by their shape. Rods, which are sort of vertically shaped, and well, they look like rods and cones because, well, they look like cones. So, rods and cones. You may have heard of these before. It's useful to get a sort of a quick feel for the difference between these things.

So let me just spit out a few properties of how these differ. Rods, there are many more rods than cones. So rods are sort of like much more popular. I think about 90% of the photoreceptors are rods, or even more than that. Yeah, so the human retina, it contains 120 million rods and only 6 million cones, so more than 90%. Rods are somewhat larger than cones. Rods are also much more sensitive to a very small amount of light. In fact, well, I've heard that human rods are capable of detecting even a single photon,

although other sources have said like six photons, but, I mean, much of a much just really. Suffice it to say, a rod is capable of being triggered by as few as one, maybe a few photons. which is still a very small amount. Cones, on the other hand, require a very much larger number of photons in order to actually produce a signal. So, cones aren't very useful in dim light. So whenever we're seeing in relatively dark light, you're basically just using rods.

The cones aren't very useful. On the other hand, when we're in bright light, like daytime, the rods quickly get saturated. And so I'll discuss what I mean by that, but essentially they become useless, and we're just seeing with our cones. So cones are for bright light, rods are for dark light. Also, cones are the only things that can see in colour, because essentially there's only one type of rod,

and it's sensitive to electromagnetic radiation over the visual region of the spectrum. It's occurred to me that I haven't actually done an episode talking about electromagnetic radiation in some detail, but basically, electromagnetic radiation can come in different frequencies or wavelengths. Those are more or less the same thing. Well, they're not the same thing, but they go together, so we'll just use the terms interchangeably for now. And different wavelengths correspond to different colors, or that's how we see them anyway. humans can only observe a very narrow range of these wavelengths, and this is called the visual spectrum. There are many other, like, infrared and ultraviolet and stuff like that that we can't see,

but that still carries energy and someone, and it's all light. It's all electromagnetic radiation, but we can only see a very narrow range of it. Rods are basically sensitive right across the visual spectrum. Cones, on the other hand, well, there are actually three types of cones. Don't get confused. Photo receptor cells, there are rods and cones. Under rods, well, there's just rods. There's only one type of rods. Under cones, there are three different types of cones.

and what are these called like L-type, M-type and S-type, but I'm not so concerned about those names. Basically, they correspond to... The difference between the different types of cones is just that they have slightly different molecules in the photo receptor molecules, which are sensitive to slightly different wavelengths of light. And this corresponds to basically slightly different colours of light. So L-type cones respond most to reddish type of colours, long wavelength, so hence L. M-type cells respond most intensely to... sort of a greenish color, which has a medium wavelength, hence M. And the third type of cells,

S-type cells, respond most heavily to blue-ish-type colors, which has a short wavelength, and therefore it's called S. But basically, so the three different types of cones correspond to red, green, and blue. And if those colors sound familiar, it's because they're essentially the primary colors. With those three colors, you can form all other colors. And it's no coincidence those are the primary colors. It's basically because those are the three different types of photos or cones that we have in our retina. So we can detect only those three different colors. And other colors that we can see are only going to come out of a combination of those three. By the way, white is formed by a combination of all of those colors, and black is just an

absence of light. So those are kind of sort of the extremes of the spectrum. They're not colors in themselves. Now, it's important to understand that three different types of cones don't only respond to that type of light. I said that they respond most to that type of light. Basically, what you can do is, like you can draw a curve, like a bell-shaped curve, which represents the height of the curve represents how much does that cell respond, and the sort of horizontal axis represents the different wavelengths or frequencies of light. The peak of the curve tells you the frequency that generates the most amount of response or most excitation from this type of cell.

So red cones peak in the red, in the red region of the spectrum, the green cells peak in the green, and the blue cells peak in the blue. But they respond to other colors as well, just not as much. So that's the key difference. Colorblindness basically results when you have, when you're missing one of those cones, or one of those types of cones, sorry, or even two of those types of cones, or you just have a deficit in the number of those cones. You might have a few of them, but not enough to generate the full spectrum of the color.

And also, just on colorblindness, it's important to understand that colorblindness is not the same thing as total absence of color vision. Total absence of color vision is very, very rare. It's called achromatopsia, and that would be very rare. Colorblindness, on the other hand, which is just inability to distinguish some types of colors. is much more common. I think 5% or something like that of males have coloured liners, so it might even be more. It's more common in males for some reason. I don't know if that's understood why. So yeah, colourblindness basically comes from lack of some types of the cones,

but not complete absence of them. Complete absence would mean you could only see in shades of grey, and that's very, very rare. Now, I still haven't explained how the rods and the cones actually detect the light. I've just explained the different types of them. So how do they do it? Well, rods and cones are basically neurons, sir. Remember that they have a cell body, the somer, they have dendrites, well, photoreceptor cells don't really have much in the way of dendrites, which take the input in, and they have axons, which are sort of the output part of the cell. Roads and cones have this sort of extra part, which is basically what makes them photoreceptors, what makes them different from regular neurons.

And basically, these are what give the rods and the cones their name. The rod is basically just like an upward protrusion of the membrane above the somer, above the cell body, and it basically just has a stack of membranes inside it. So remember, the outside exterior of the cell is surrounded by the cell membrane, but within that you can have sort of subsidiary membranes. Vesicles are an example of that where you have a membrane inside the cell surrounding some, like a neurotransmitter or something or some other proteins. These membranes that I'm talking about are not vesicles. They're bigger than vesicles, or I think generally bigger than vesicles, they're kind of pancake shaped. It's basically like a whole bunch of pancakes stacked on top of each other. And that's why it's a cone because, sorry, that's why it's a rod, because basically it literally looks like a rod that points upwards from the somer,

And then inside that rod is just a stack of these internal membranes that kind of look like pancakes, and there's a bit of a gap in between each of them. The cone has a similar structure, except that the membranes are sort of like that. They get smaller as you move upwards, and so hence the cone shape. And it's a bit, it's not quite as tall as the rod, but it's similar type of thing. You've got a bunch of membranes inside the overall cell membrane. What's the point of these membranes, or these internal membrane disks? Well, embedded in the membrane of these disks are the actual photoreceptor molecules.

And these photoreceptor molecules are what does the actual. actual transduction. So the cones and the rods have slightly different types of photoreceptor molecules. The cones have a molecule that's called photopsin, and the rods have a molecule that's called rhodopsin. So, I mean, they have very similar names, and that's because they're very similar molecules. They're almost exactly the same, really. They're just slightly different. And remember, photopsin is found in all the cones, but what makes the cones different from each other, because remember there's three different varieties corresponding to three different colors. It's just because the confirmation of photopsin is slightly different in those different varieties of cones.

Confirmation, basically, that just means the shape of the protein, basically, or the molecule. Shapes a bit different, so it reacts with light a bit differently, and therefore it absorbs different wavelengths at slightly different levels. So that explains why you've got the three different types of cones that respond differently to the three different frequencies of light. But what I'm going to mostly talk about is rhodopsin in the rods. sorry, rhodopsin in the rods. I think it's been studied a bit more than the photopsin in the cones, so we know a bit more about it. But the fundamental process is almost exactly the same. There's just maybe some minor differences with the precise metabolic pathways and so on.

But that's not so important for our purposes. We just want to get a basic idea of how it works. Okay, so now that we've talked about the rods and the cones in gory detail, I'm now going to talk about rodopsin in more detail. So remember, we're specifically talking about the rods now, because rhodopsin is found in those stacked membranes inside the rod. odds, but cones, very similar principles. Okay, so Rhodopsin is a chromo-protein, which means it's a protein,

remember from biochemistry basics what a protein is, just amino acids are chained together and wound up in an interesting structure. It's a protein linked to a pigment-carrying substance. A pigment is a substance that selectively absorbs some particular wavelength or wavelengths of light. So basically anything that you can see that's not white, that's not completely white or transparent, has some pigments in it. pigment just means that it absorbs some colors preferentially, and so you can sort of see it.

So, paints all contain pigments, for example. Any color paint, it's going to have to have some pigment that preferentially absorbs all of the colors other than the one you want to see. So yellow paint has to absorb all of the colors apart from yellow and reflect yellow so you can see. So pigments are all over the place. So it's a fancy word for something that's actually quite common. When we say rhodopsin is a chromoprotein.

Rodeption is a molecule, well, a big complex molecule, which is comprised of a protein bit and a pigment bit. the protein bit is called opson, hence, not rhodopsin, and the non-protein bit, the pigment bit, is retinal. So, rhodopsin is opson plus retinal, sort of bonded together. Now, the opson, the protein bit, is just a bundle of seven transmembrane helices connected to each other by protein loops. So what's all that means? So trans membrane just means it goes across the membrane. So remember, we've got these intramembrane disks, and basically studded in those, across the membrane, is this opson molecule, and the opson molecule is comprised of helices. So that's basically,

you know, like the double helix in a DNA. It's just a particular shape that proteins can have as part of their structure. You've got a bunch of these helices that are all connected together, and they're all seven of them, exactly, they're all connected together, and they're all part of the same protein. They're all part of opson, but they just studded sort of separately into the membrane. The precise structure of that's not that important, I just wanted to give an idea of what the molecule is like. So it's a bunch of helices connected together, studded in the membrane. Bonded to the opson is the retinal, which sort of lies horizontally

with relation to the membrane. So if you can imagine the membrane, it goes across, studded in that membrane, we've got opson, which sort of pokes out at either end, and that's comprised of its seven little helisy components, but they're all sort of bunched together, and then sort of bonded to the opson, but sort of lying horizontally underneath it, so inside

the pancake membrane, internal membrane, is the retinal, which is the actual pigment molecule. So the outer, the outer disc, or remember this is a pancake in a membrane contains thousands of these rhodopsin molecules. So they're all studded at different locations around the membrane. Okay, so that's the structure of the whole rod thing. So we've got a rod with a sort of a rod shape, protrusion of the membrane. Within that, there are a bunch of

essentially stacked internal membranes. Studded inside these internal membranes are each of the membranes containing thousands of these rhodopsin molecules that stick out on either side of the internal membrane. And each rhodopsin molecule in turn is comprised of the opson bit, which is a protein that's actually in the membrane, and the retinal bit, which is the non-protein pigment part of the rhodopsin chromoprotein, which sits just inside the membrane disc. Hopefully you can sort of picture that. Now, we're finally going to talk about the actual process of phototransduction, which just refers to the process of converting light into an electrical signal. So how does this occur? The first thing that has to happen is a light, so a light photon. A photon comes in, it's refracted

by the cornea and the lens and so on, and it falls on some region of the retina. In particular, I mean, photons are quite small, so they're going to fall on a particular cell of the retina, and even more specifically than that, they're going to fall on a particular photoreceptor molecule of that cell. Obviously, if they fall on a part of the cell that does not contain a photoreceptic molecule, while they won't be detected, they won't do anything interesting. You're only to detect the photon if it actually falls on the right part, if it makes sort of directly falls, like literally makes contact, in so much as we can talk about, you know, contact in a sort of an atomic level here.

But basically, think about, like, the photon literally comes in and hits the particular odopsin molecule that's sitting inside the membrane. What happens? So the photon has to hit the retinal itself, that is the pigment part, you know, that's sitting inside the membrane. It's got to hit that in order for phototransuction to occur. So it's a fairly sort of a narrow target, but remember there's lots of photons coming in like, I don't know, trillions, heapsed of them. So some of them are going to hit the retinal in various different of these rhodopsin molecules sitting around the retina. When the photon, and the photon, of course, also has to be of the correct wavelength, the frequency, otherwise it won't do anything. So when a photon of the correct frequency hits the retinal, the retinal undergoes isomerization, which just basically means a change in its shape. Basically, the technical term for that is it changes from an 11 cyst to an all-trans configuration, which essentially just means that it goes from being slightly bent to straight,

if we want to think about it like that. So it's a bit bent, the photon hits it, it undergoes isomerization, changes shape, and it becomes straight. Now, why is that significant? Well, because it's no longer bent, it no longer fits inside the binding site that it has to, It needed to be bent to fit in quite properly. It doesn't really fit anymore. And so what happens is that opson itself undergoes a conformational change to some other protein. We don't need to know its name.

I mean, it's the same thing. It's structurally the same. It's just shaped a bit differently because the retinal sort of stuffed up the shape that it was in before, and so now it changes its shape. The new protein that Opson changes into, or just the conformational form of it, is unstable and splits into two. So basically now what happens is the Opson and the retinal split apart, because previously they fit together nicely,

but now that they've changed shape, they don't fit together properly, so they split apart. Okay, so now we've got opson and retinal going their separate ways there. Well, they're not quite option in retinal anymore. So now we've got opson and rationale, which are disassociated from each other, and they've gone their separate ways. The opson sits around, basically, it's still embedded in the membrane, the retinolts away into the cytoklasm. Why do we care about that?

What relevance does that have to actually vision, transduction? Well, it's what happens afterwards that's important. So the opson that's still sitting around in the membrane is now no longer attached to the retinal, and so that basically allows it to bind to something else. Specifically, it binds to a regulatory protein called transducin. The transdution was just sort of sitting around inside the membrane or nearby before the photon came and began this whole process. But now that the retinels moved away and the opson

changed its confirmation a bit, the transducian is able to bind to the optin. And why is that important? Well, because this binding changes, again, change it slightly, changes the shape of the transdution, which is this regulatory protein that was sitting around. And it causes the the transducin, the transducin, to dissociate from a GD. D.P molecule with which it was bound and instead bind a GTP molecule. Now, these are just energy molecules. It doesn't really matter what they are. But the point is, the transducin binds to the opson, which is now free from the retinal, and as a result of that, the transduction itself becomes unstable and breaks up into two subunits. We're called the alpha and the beta subunits, I think, but again, that doesn't add it too much. The transducin bonds to the opson breaks up into two because, again, it becomes unstable and it's in its existence confirmation. Why do we care about that? Well, it's because of what happens next. So we're going to get there in the end.

But it's like many essentially metabolic or protein pathways, secretary-message of pathways in the human body. It's sort of very indirect. It's like, why are you doing it this really weird way? But that's how evolution works. We've broken up the transducine protein into its, into two components. One of these components binds to and activates a photodiesterase, which is an enzyme that breaks phosphate bonds.

Phosphate bonds are just a particular type of bonds that are found in many biological systems or molecules, which, again, had been floating around in the cytoplasm. So this, this fostodiasis, was floating around, and then when it came across the alpha subunit of the previous transducin protein, it binds together, and so that it can now break the phospho bonds. Previously, it was inactivated. Now, it's changed shape so that it has been activated.

That's very important, because now the phosphodiesterase begins to break down another molecule called CGMP. Again, it doesn't really matter what this other molecule is, but the CGMP. CGMP is crucial because the rods contain sodium channels in the external membrane. not the pancake internal membranes that I've been talking about that contain the rhodopsin. This is the actual external membrane of the cell itself. This is started with sodium channels. I mean, it has many types of ion channels, and we talked about this in the previous episode

about neurons and synapses, but among those are CGMP-gated sodium channels. Now, normally these channels are open, which means sodium channels are free to move into and out of the cell. However, phospho-diesterase breaks down the CGMP, and these sodium channels need the Cigms. in order to stay open because they're CGMP gated, which means the CGMP has to come along and bind to the ion channel. And without that binding, it will close. So, phosphodasterase breaks down the CGMP, which in turn means the sodium channels close. When the sodium channels close, this causes a hyper-polarization of the cell.

So remember, there's a resting potential, this is from the neurons and synapsis episode. There's a resting potential of the cell of roughly negative 70 millavol. So there's a small negative charge in the cell as a whole. Hyper-polarization means the cell becomes more negatively-chisement. charged. And that will happen. So, in other words, the cell will become hyperpolarized if you stop sodium ions from entering the cell through it through the membrane, because sodium ions are positive to charge. So when those are coming in, that helps to maintain a more positive charge of the cell. You stop those from coming in, the cell is going to become hyperpolarized because

you're keeping out these positive charges. And the CGMP-gated sodium channels are crucial for allowing those 30-miles to come in there by maintaining the resting potential. You close off the CGMP-gated sodium channels, you stop the sodium miles from coming in, you cause the cell to hyperpolarize. Hyperpolarization of the cell, in turn, causes the voltage-gated calcium channels to close. So these voltage-gated calcium channels are just other channels, that instead of being gated by CGMP,

they open and close according to the voltage of the cell, the charge, basically, the charge concentration. So, when the cell becomes hyper-polarized, these voltage-gated calcium channels close, because basically they only stay open so long as the polarization of the cell doesn't become too negative, When it gets too negative, they shut down, the calcium ions can't come into the cell. When the calcium level in the photoreceptor cells drops below a certain level, the amount

of the neurotransmitic glutamate that is released by the cell also drops. This is because the calcium is required in order to cause the glutamate containing vesicles to fuse with the cell membrane and therefore dump their content, sorry, into the synapse. And that, in turn, the change of the amount of glutamate that these photoreceptors are putting out, in turn, basically leads to greater potentials in the cells that follow. They don't actually directly lead to action potentials, which is a little bit odd, but we'll get that in a moment. But basically, this dumping out, or actually, this change in the amount of neurotransmitters that you're dumping out is the crucial thing that we want to generate. This is the final stage in the transduction, basically, because once you get the neurotransmitters changing the amount of action potentials, essentially, that's occurring in the neurons, that is the type of information that brain understands.

So getting to this stage is sort of the whole goal of the process. So we start with photon hitting the retinal and changing its confirmation and end up with, a change in the amount of neurotransmitters that we've got. That whole process is called transduction. So it's quite complicated. I'm probably thinking I lost a number of you in this description. So I'm going to go through it again and try and summarize it so that we can get a picture of what's going on here. So remember, the first stage is that the photon comes in, hits the retinal, which is the pigment molecule, changes its shape. Retinal no longer fits into the opson, which is the protein path. As a result, the opson and the retinal

disassociate. And then what basically happens, is a number of stages, sort of secondary messenger, sort of a cascade of chemical reactions occurring, one thing bonding to another thing, which bonds to another thing. Eventually that ends up with the phosphodiasterase enzyme is activated and begins breaking down CGMP. When it breaks down CGMP, the sodium channels close. When the sodium channels close, sodium ions stop coming in the membrane. This causes hyperpolization of the cell, which in turn means that the calcium ion channels now close. So there's two types of ion channels here. The first are the sodium iron channels, these are CGMP gated.

We shut these down by activating phosphodiasterase, which is an enzyme that breaks down CGMP. CGMP is not around anymore, and therefore you can't unlock the gate, basically. Sertium iron channel gate. So the sodium channels close. That hyper-polarizes the cell and leads to the second type of iron channels closing,

which are the voltage-gated calcium ion channels. And this is actually the crucial part, because it's the calcium that is essential to cause the vesicles that are also just sitting around inside the, the photoreceptor cell, these vesicles which contain glutamate, a neurotransmitter, require calcium in order to fuse with the external membrane and dump out their neurotransmitters. When we've got no calcium, because the voltage-gated ion channels closed off,

the vesicles stop fusing with the membrane, and the cells stops dumping out, glutamate, or at least reduces the amount that it dumps out. It's important to understand that the photoreceptor cells themselves do not produce action potential. So this is not like your standard neuron where you get inputs through the dendrites and you get graded potential, which eventually, if they cross the threshold, lead to an action potential and then that causes the vesicles to fuse with the membrane dumping out the neurotransmitter and then causing greater potentials in the post-synaptic neuron. That's not happening here. All we've got is essentially greater potentials, which

eventually cause a change in the amount of glutamate that you're dumping out. There's no actual action potential that occurs here. So that's a bit different. So this entire process is basically just a way of changing the amount of glutamate that we're dumping out into the synapse. In order to change the amount of glutamate that we're dumping out, we need to change the amount of calcium that's sitting around, because calcium is what causes it. binds with the vesicle membranes and causes the gluteumat to be dumped out. In order to change the amount of calcium that we have around in the cell, we need to close the voltage-gated calcium channels.

In order for those to close, we've got to hyper-polarize the cell. Well, how do we hyper-polarize the cell? We do that by shutting down the sodium ion channels, which are bringing positive charges into the cell, and therefore stopping it from being hyper-polarized. How do we shut down the sodium channels? We get phosphodiasis to be activated and break down the CGMP molecules that are allowing the sodium,

channels to be opened up because they're CGMP gated. How do we get phosphode airstriase to be activated? Well, that's where we get that alpha subunit of the transducing protein. We get that bit of the transducing protein, which is able to bind to and activate the phosphodercase. How do we get that alpha subunit of the transducian molecule? Well, we need option to bind to transducation in order to break up, in order to break up the transducing into a couple of subunits, and then the subunit activates the phosphodosterase. The phosphodercase breaks down the CGMP. the CGMP-gated sodium channels close, and that leads hyperpolarization, and then the amount of... The hypopolarization leads to the calcium-gated ion channels to close,

which therefore causes the vesicles not diffuse with the membrane, and therefore the gluteamate is not dumped out anymore into the synapse. Jumping right back to the start again, how do we get that transducine to be broken up into the different parts by the obson molecule? Well, we've got to get the obson molecule by itself, and to do that, we have to get it to be separated from the retinal, because to start off with the opson and the retinal are connected together into this complex, which we call rhodopsin.

How do we get the opson molecule by itself so that it combined with the transducine and therefore activate the phosphodestriates and so on? How do we get the option by itself? We need to change the confirmation of the retinal, because once we change the confirmation of the retinal, change the shape of that retinal, the rhodopsin complex will be unstable and break apart. How do we change the confirmation of the retinal? That happens when a photon falls onto the retinal and changes its confirmation,

because basically it puts it up into high-energy state, as this important think about it. And so that's where the photon comes back into it. That's where the light comes back into it. The photon hits the retinal, changes its shape, and then we get this big cascade of events, which ends up with the concentration of calcium inside the cytoplasm declining, which means that the glutamate containing vesicles no longer are fusing with the cell membrane, and so we're not dumping out glutamate into the synapse. Okay, so I'm going to leave it there for this episode. We'll pick up with the rest of the story by discussing the remaining layers of the rationer, and then moving on to processing of the visual information in the brain and the lateral genicular nucleus and V1 and so forth in future episodes. It looks like we're probably going to have two more episodes, maybe three more. This podcast has already gone over long, so I'll dispense with most of the usual things that I say now. One thing, though, that I did want to mention was that my podcast was recently mentioned on another science podcast,

which some of you may have heard before and may not called The Sudo-Scientists. That's a podcast run by some friends of mine. In that podcast, they talk about science news topics, the role of science in society, and how science is sometimes misunderstood, all sorts of things like that. I think probably most listeners of my show,

if you're interested in science, you'll like that podcast as well. So go check it out. Just type The Sudo-Scientists, pseudoscientists being one word, into Google, and you should be able to find them fairly easily. So, on that note, thanks for listening, and I'll talk to you next time.