Good morning. So welcome.

Um, this is the going to be the first of two lectures

that you're getting both on the same day about the visual system. So vision, as
you probably know, is a very important primary sense for humans and very many
different species. Does anyone know who's iris is, by the way? There will be a
prize this afternoon if you. Almost know the right answer. It's a cuttlefish. Yeah.
Close. Um, so vision is very important. Primary sensor. And in the course of these
two lectures today, we're going to only scratch the surface of the visual system.
But we will try to look at two important processes that are mediated by the eye.
So the first is the conversion of light energy and environmental signal into an
electrical biological signal. This is the process of photo transduction which we will
look at this morning. And then we'll move on again this morning to look at the
role of the AI in neural computation. So we'll examine how circuits in the retina,
um, process the visual scene. And we'll see how feature extraction and parallel
processing generate a compressed representation of important sensory salient
sensory information that is important for guiding behaviour and is communicated
to the brain through the optic nerve. Um, then in this afternoon's lecture, we will
firstly, we'll have a mental meta quiz to see if you learnt anything this morning.
Then we will talk a little bit more about retinal processing, and then follow the
rest of the physical pathway from the retina to the visual cortex, which is thought
to be the main route to supporting conscious visual processing. And then after
that, we'll have another mental meta quiz. Um, and you can see if you do any
better on the second quiz in the first. So this morning's lecture is going to cover
some very basic stuff about the AI in the visual fields. Um, introduce some
important, um, principles of visual processing in the retina. We'll look at its
structure and connectivity, and then we'll spend most of the time looking at
photo transduction. Um, a very important process which is going to capture light
energy and generate the biological signal and photoreceptors and then start
looking at retinal computation, focusing on the famous on and off pathways. This
is the bit where you'll need to pay special attention. So the eye, as you know, is
the organ of vision. And across the, uh, across the, uh, uh, natural world, there's
a wide variety of different eye designs. Um, humans and other vertebrates have
what's known as a camera type eye, which is shown here. So you probably are
familiar with the anatomy of the eye. But these elements that the at the front,
these optical elements, the crystalline lens and the cornea are refractive
elements that are responsible for bending incoming rays of light and generating
focussed images on the photosensitive surface at the back of the eye. Much like
the lens of a camera generates a focussed image on a film, or nowadays on the
CMOs sensor in the eye. Despite sensitive surfaces, the remarkable neural retina
which we're going to be focusing on a lot today. There are also various muscles
associated with the eye, so muscles in the ciliary body can change the shape and
optical power of the lens. This is a process known as accommodation, which
allows you to focus on objects at different distances than the outside world, and
muscles associated with the iris can change the size of the entrance pupil of the
eye, so you can adapt to different light intensities, see in bright sunlight and also
in dimmer conditions. There are also six extra ocular muscles, only two of which
are shown in this cross section, which are attached to the outside of the eye. The
globe which allow the eye to rotate around three different axes in the orbit. So
that's the sort of basic anatomy. But as I mentioned, there's a wide variety of
different eye designs in nature. We've looked at cuttlefish eye. This is the eye of
the compound either fly which has a radically different organisation.
Unfortunately, in these lectures we're really going to focus on, um, mammalian
or specifically primate vision. But you should be aware that there's a lot of
variety. So the eye is obviously a sense organ. And in thinking about a sense
organ, we have to consider, um, what region of of stimulus space, what region of
the environment is accessible to the eye. And this is known as the visual field. So
the visual field is defined as the region of space in angular terms that the eye
can see. Um, the monocular visual field for the human eye is about 170 degrees
in the horizontal plane. So these red rays here indicate the limits of the visual
field. For the right eye it's about 170 degrees quite large a bit less than the
vertical dimension. Um, but one thing you have probably noticed is you have two
eyes. And this has a number of important consequences. So the first is that your
total visual field is enlarged beyond what one I would see on its own. And
secondly, because you're a primate and you have both eyes on the front of your
head, your monocular visual fields overlap, generating a so-called binocular
region. This is about 120 degrees in humans. And binocular vision has a number
of important consequences for the visual system, one of which is that it supports
a mechanism for depth perception called stereo. This. This is a binocular
mechanism for depth perception, and this arises because your eyes are
separated on the head. They obtain slightly different parallax views of objects in
the outside world, and your brain can fuse those two images to generate three
dimensional perception and depth. Perception is one of the functions of binocular
vision. Um, in thinking about this visual fields, though, we said 170 degrees for
one eye. It's not sampled evenly, and this arises due to the structure of the eye
and particularly the retina. So one important feature is that the retina has a
region called the optic disk. This is where the optic nerve joins the eye and blood
vessels enter and exit the eye. At this point, there's a gap in the photoreceptor
layer which generates a blind spot, so any regions of visual space cast onto the
optic disk are invisible to this. I usually don't notice this when you're viewing the
world of two Eyes. It's one of the advantages of binocular vision. The second sort
of feature of the retina is that in many species, including humans, there's a
specialised region called the fovea, which is responsible for very detailed high
acuity vision. So regions of visual space cast onto the fovea a perceived in
greater detail. We'll see why later in this lecture. But the fovea only covers a
couple of degrees of visual space. So it's about the width of two fingers at arm's
length. Only the small sliver of visual space can be viewed at high resolution by
the phobia. So again the retina is a heterogeneous structure, something we're
going to keep returning to in this lecture and thinking about the eyes and the
visual field, though. One thing you might realise that the eyes can move. So this
is illustrated here by one of the masters of eye movements. Obviously it's a
chameleon, not a primate. Eye movements serve a whole variety of important
functions of the visual system, which unfortunately, we're not going to go into in
any depth. But I'm going to briefly give you a flavour of three types of voluntary
eye movement in these next couple of slides. So one voluntary eye movement
that you should be aware of is known as smooth pursuit. The function of smooth
pursuit eye movements is to maintain images of moving objects on the fovea. So
this process of tracking objects and keeping them fixed on the face is known as
your fovea. Eating the object. So this interesting object moves backwards and
forwards your eye. Both eyes will rotate alternately clockwise and then counter
clockwise in order to maintain foliation of this target. So you're probably doing
smooth pursuit now if you're tracking this laser pointer and slowly getting
hypnotised. So this example of an eye movement is quite slow and both eyes
rotate in the same direction. They're both rotating at any instant, either
clockwise. The target's moving this way or counterclockwise this way. That's
known as a conjugate eye movement because both eyes are rotating in the same
sense, clockwise or counterclockwise. And that contrasts with our second
example, the vergence eye movements, which are important for fabricating
targets in depth. So if I, for example, fo gating this laser pointer and it moves
towards my nose, my eyes need to converge. They both rotate towards the nose
in order to maintain focus of this target. So viewed from above, one eye is going
clockwise and the other counterclockwise. That's known as a disjunctive eye
movement. And as you can imagine, and obviously if the target moves away, the
eyes diverge. So these eye movements, as you can imagine, are very intimately
linked with stereotypes. And both classes Neath the seat and vergence are
controlled by quite complex circuits that span from the brainstem all the way
through to the frontal cortex. These are also quite slow, smooth eye movements,
and that contrasts them with our third example of an eye movement, which are
saccades. Saccades are very fast, ballistic eye movements which allow the eye
to very abruptly change position in the orbit, and they're separated by, um, by
periods when the eye is relatively still known as fixations. So these rapid, abrupt
changes in eye position, um, allow you, in combination of head movements and
movements of the, of the whole body, sometimes to redirect gaze, to explore a
visual scene. Um, this is illustrated here. So this is the pattern of saccades, these
quick lines and fixations, the little blobs that the human is doing as they inspect
this interesting artefacts at the museum. And, um, the important reason is the
reason you need to perform this sequence of psychotic eye movements is to
allow you to successively sample different parts of the visual scene with your
fovea. Remember I told you the favourite only covers a tiny little slit? There are a
couple of degrees of visual space. If you want to build up a high resolution
picture of an object of interest, you need to successfully sample from the visual
scene using these successive psychotic environments. Saccades are extremely
fast, so the eye can rotate around 900 degrees per second. In primates, it's one
of the fastest movements that you can make. But even during the fixations in
between the saccades, the eye is not really static. So small fixations, eye
movements, they're called vertical drifts, tremors and microseconds mean that
the eye is constantly moving even during the fixation. And that is important to
prevent images being perfectly stabilised on the retina, because stabilised
images fade very rapidly from visual perception. So these fixation eye
movements are tied to character actors. So this is a very inadequate survey of
eye movements. You should be aware that there's several other types of reflex
eye movement in addition to the ones I've talked about, which also important for
us for normal vision. But we won't go into any more detail about eye movements
today. So we're going to touch now on some basic principles of vision and start
thinking about how the how the eye functions in, in, in capturing light energy and
generating visual perception. And one very important thing you should take
away from these lectures is the eye is not going to perform like a simple camera.
It's not going to acquire a faithful image of the outside world and then sort of
ship this image off to the brain, but to do all the processing instead, it's going to
do a lot of data compression and feature extraction. So let's start by to try to
understand what I'm talking about, looking at this very simple image. So on this
uniform background, this grey bar appears to have uniform intensity from one
end to the other. Pretty boring right? But if it's superimposed on a gradient
background, it doesn't look uniform anymore. So the bar hasn't changed, of
course, but the way that you perceive it has when it's overlaid on a different
background. And this very simple example illustrates a very important principle
of retinal visual processing, which is that the retina is very interested in
differences in light intensity across space and also across time. So the right hand
edge of the bar, the bar is relatively brighter than the background, relatively dark
in the background, sorry. Whereas the left hand end is relatively brighter than
the background. And the retina is particularly interested, as I said, in these
relative differences in light intensity, in this case across space, which is known as
spatial contrast, and spatial contrast is but one of several. What's going on now?
Several visual features that the retina extracts were sensitive to. A couple of
others are listed, a few others listed here. So the wavelength. The retina is also
sensitive to the wavelength of light, which as we will see, will lead is responsible
for the perception of colour. So this is the visual feature and this is the first set.
And as we've seen writing is sensitive to spatial contrast. The differences in the
lighting intensity across space, which allows the perception of edges in visual
scenes. And it's also sensitive to spatial frequency, which approximately
corresponds to the size of visual features. There are many other aspects of
feature sensitivity two one, for example, is motion, so the retina can detect
motion and motion direction. But we're not going to touch on this slightly more
complicated topic. Uh, very much. We'll mention it briefly in the second lecture.
So before we go on, it's very important that you have clear in your mind what
spatial contrast is and what spatial frequency is. on this slide is supposed to help
illustrate this. So this is an image. It's a sinusoidal grating. It doesn't really
matter in which both contrast and spatial frequency vary. So contrast as I
mentioned before, refers to differences in light intensity across space. At the top
of this image, contrast is high. So there's a very large difference in intensity
between these bright white bars and these dark black bars. And towards the
bottom of the image contrast decreases where both the white and the black bars
move towards this mid grey level, and you find it very hard to see them. Spatial
frequency refers to the length scale over which these contrast modulations
happen, so on the right hand side of the image, spatial frequency is low. That
corresponds to long wavelengths. And you can see these very broad white and
dark bars. Whereas on the left hand side of the image the spatial frequency is
high, that corresponds a short wavelength. And you can see these very narrow
closely spaced bars. So the reason this is important to understand the difference
in spatial frequency and contrast, and think about these features, is that natural
scenes contain a broad range of contrast and spatial frequencies that the retina
needs to be sensitive to. So one, um, uh, uh, aspect of retinal processing, which
we're going to encounter in these lectures is the concept of parallel processing.
And what this means is that essentially there are going to be different
populations of cells in the retina which are responsible for extracting a particular,
in this case, spatial frequencies from the same input image. So panel A is
supposed to show an input image might be familiar to you, which has been cast
onto the retina. And in these three other panels we're looking at the
representation generated by a particular population of cells. So in B, a population
of cells which are tuned to low spatial frequencies have extracted a low spatial
frequency representation of Westminster Tower. Whereas other populations of
cells are extracting medium or very high spatial frequency information from the
same scene. So this is happening by separate population cells at the same time,
in parallel to generate multiple representations of the same input image, which
are going to be communicated to the brain to support different aspects of
behaviour. And over the course of this lecture this morning and this afternoon,
you will hopefully come to understand exactly how this comes about, or more or
less exactly how it comes about in the retina. So this idea of taking an image and
splitting it into multiple representations feature tuned representations as is
parallel processing. So let's now dive into the retina and see how it does, how it
detects light and does all this neural computation and parallel processing. So
we'll start by reviewing the structure of the retina. You've probably already
somewhat familiar. So the retina is actually a very well studied part of the central
nervous system. And importantly it is part of the central nervous system, not the
peripheral nervous system. So you might know if you've done some
developmental neurobiology that early in development, the neural the neural
plate if originate some complicated morphogenetic movements generate the cup
shaped retina of the two eyes. The it's part of the CNS, as I've said, um, it's a
layered structure. So it has multiple layers of cell bodies and synaptic neuro pills.
And here we can see the, the basic arrangement. So up here at the top are the
photoreceptors. Um, these are going to be the site of light capture that are really
going to convert an environmental signal light energy on the one hand into an
internal neural representation. So they're kind of the interface between the
outside world and the internal neural representation. And that's going to support
vision. Um, rather counterintuitively, they sit right at the back of the retina. So
incoming light has to pass through all of the other cell body layers, at least in the
mammalian retina, before reaching the photoreceptors in an octopus, by the
way, it's the other way around. But for primates, the facial receptors at the back
information then is passed from the photoreceptors to bipolar cells down into
neurones in the retina, and then from the bipolar cell, information can be passed
to retinal ganglion cells. These are the output cells of the retina, which are going
to project long axons through the optic nerve to reach the retina recipient targets
in the brain. So that pathway just went through from photoreceptor to bipolar to
ganglion cell is the most direct route for visual information. It's the so-called
vertical pathway. If I. Guess the vertical pathway through the retina. But there
are also other populations of injured neurones which mediate a process of lateral
information flow. And we're going to encounter two examples on this morning
and on this afternoon of of that and why it's important. Another important thing
to note is that a lot of the neural signals in the retina are mediated by graded
changes in membrane potential. They support a lot of the neural activity in the
retina, but ganglion cells, the output cells, are spiking neurones. They fire action
potentials suitable for long distance communication along the long optic nerve all
the way to the brain. Hopefully you know the difference in graded potential
changes and action potentials. So let's start by looking at the photoreceptors
then and look at the process of photo transduction. As you might know, there are
two main flavours of photoreceptor in the eye the rods and the cones shown here
in this beautiful light micrograph. So these are rods and these are cones. Two
cones here or three actually. And these two main populations of photoreceptors
have different structures, different physiologies different functions and different
distributions across the retina. So the rods this is now a scanning electron
micrograph. You can see lots of rods here. These things are responsible for very
high sensitivity Vision. So they're extremely sensitive to light. And they support
your vision at very, very low light intensity, so-called psychotropic vision at night.
Um, the rods are very abundant. So they outnumber cones about 20 to 1 in the
primate retina, and they're distributed across almost the entire retina. So in this
plot here, you're looking at the distribution of the photoreceptor sites measured
across the surface of the retina, where we're measuring in degrees from the
phobia. So the fever is here at zero degrees. And then we're measuring it
degrees eccentricity from the five year. And hopefully you can see that the rods
are kind of distributed everywhere except at the phobia where they're absent. So
that's the one region that they're excluded from. And instead at the table we find
the other type of photoreceptors, the cones. So the cones are responsible for
vision at higher light intensities, which is called for topic vision. So you're using
your cones now in this bright, um, lecture theatre. Um, there are three types of
cones which as we will see, support colour vision. And they are very sparse
across most of the retina, except for the phobia, where they're the only
photoreceptor type present. So again, the the retina has a very heterogeneous
structure. I mentioned at the start of the lecture that the phobia is responsible
for high acuity vision, and this arises for several reasons. So this cartoon doesn't
really illustrate this very clearly, actually had a phobia. We've said only cones are
present, but the cones that are found at the phobia are very small and squished
together. So this means that because they're packed in very tightly, each
individual cone only views a tiny sliver a fraction of a degree of visual space. And
the circuitry of the retina is designed to keep this visual information separate. So
what this means is that these individual fovea cones have dedicated private
connections through the retinal circuit onto ganglion cells. In fact, one cone can
connect to, on average, about 2.5 ganglion cells. Um, this means that the
rational circuitry does not mix visual information from adjacent cones. It's kept
separated, and that's responsible for visual acuity. This tight spacing of the cones
really sets the limit on the resolution of your vision, the limit of visual acuity. This
sort of private connection scheme is not a present in the peripheral retina. So out
in the periphery, many cones. In this cartoon only three. But in reality it can be
thousands of cones or thousands of rods and converge onto individual ganglion
cells. So this results in a pooling of visual information from many photoreceptors,
which decreases visual acuity, visual acuity. So the resolution of vision is poorer,
but it does have the advantage of it increases visual sensitivity because you're
summing the light signal that's derived from many photoreceptors. The
peripheral retina is better for visual sensitivity and for motion perception. The
flavour is better for high acuity, detailed vision. Okay, so let's have zoom in on
some photoreceptors and look at their, um, the structure of the cells. So
photoreceptors, the cells and cells can be divided into three main sections. The
important business end is called the outer segment. So rods shown here in this
micrograph have very long rod shaped outer segments. Um and these outer
segments contain very large numbers of flattened membranous compartments
called discs. The discs are a little bit like a stack of coins inside the outer
segment. They're shown here in cross-section. And these, as we're going to see,
are going to be the size of light capture. So the rods have very long outer
segments containing tons of discs full of photo pigment for light capture. Cones,
on the other hand, have shorter cone shaped outer segments. And they're these
flattened, membranous compartments at all lamellae. They have a different
name in cones. The second part of the photoreceptor is that the inner segment.
So this contains the cell body in the nucleus and lots of mitochondria to generate
energy for potential destruction. And then finally the cell has a synaptic terminal
where it releases neurotransmitter onto downstream cells such as bipolar cells in
the retina. And in the case of photoreceptors, the neurotransmitter is glutamate.
So as I briefly mentioned, it's in these disc or lamellae membranes that light
capture is going to happen. And the reason that the light is captured there is that
these disc membranes, in the case of rods, are packed full of molecules of photo
pigment in this slide. So photo pigment itself is made up of two main ingredients.
The first is the protein and oxygen. In rods. It's called rhodopsin. Easy to
remember I've shown here in blue this is a seven transmembrane protein. And
you can see its seven transmembrane helices helix crossing the membrane. The
second ingredient is a retinol cofactor derived from vitamin A, which is covalently
bound that shown here in red and is covalently bound to a lysine residue on one
of these transmembrane helices. So together, the option and the rationale
cofactor comprise the photo pigment. And this retinal cofactor is important
because this is actually the chromosphere which is going to absorb light. And the
way that light capture works is that it's going to induce a conformation will
change what isomerisation of the retinal cofactor, converting a cis carbon carbon
double bond to a trans carbon carbon double bond, so that retinol changes from
11 cis retinol into all trans retinal. And that process is known as photo
isomerisation. The absorption of a photon causes the change in the structure of
rationale from 11 cis to all trans. And this is really the crucial event that this
bridge British represents the capture of the photon, and it's going to be
propagated because the change in the shape of the retinal chromosphere will
induce the conformational change in the opt in protein, which allows it to interact
with the hetero trimeric G protein, as we will see, and kicks off a whole cascade
of events in the photoreceptor, which eventually results in a change in glutamate
release. We're going to come to that cascade in a couple of slides time, but it's
all initiated by this initial photo isomerisation event. So both rods and cones are
two main types of um photoreceptor contain um photo pigment um, but they um
contain slightly different types of photo pigment which result in sensitivities to
different wavelengths of light. So this sensitivity is shown here in this plot. So
this is wavelength on the x axis. And this is log sensitivity on the y axis. All rods
share the same photo pigment which we said is called rhodopsin. And as a result
they all have the same spectral sensitivity, which is illustrated here in black. It
peaks around 500 nanometres, a sort of greenish colour, and then drops off at
longer wavelengths. Um. However, there are three types of these. In primates,
there are three types of cone, each with a different type of cone of sin. So for
example, the s cones contain s Hopsin s for short, uh, and they're colloquially
known as blue cones because short wavelengths correspond to the perception of
blue colours at their sensitivity shown here. This blue trace. There are m cones M
for medium containing an option with the sensitivity shown here in this green
trace. And then finally L cones containing an L and L for long, which are tuned to
the longest wavelengths globally known as red cones. Um, the reason that each
population of cones has a different spectral sensitivity is because of differences
in the amino acid sequence of the oxygen, so the retinal cofactor is the same in
all cases. The amino acid sequence of the oxygen that's illustrated here is
responsible for these differences in spectral sensitivity. And this difference in
spectral sensitivity is illustrated again on this slide. Now we're not on a log scale
which is why these curves look a bit different. Um, because we have three
populations of cones in the primate retina with different spectral sensitivity. This
is this supports colour vision. And the reason that it allows you to perceive colour
is going to be hopefully illustrated here. So in response to any individual
wavelength of light, the light of this particular wavelength, let's call it 590
nanometres is incident on your retina. As you can see, this wavelength is going
to cause very strong activation of your L cones. About half as much activation of
the M cones. And no activation at all of your S cones. And that ratio of activation
levels, the relative levels of activation. High, medium and none can be decoded
to perceive um in this case for colour yellow. So the relative activations of the
cones is responsible for colour vision. Um, this also makes clear to you hopefully.
Why the why road vision or topic vision at night is is achromatic because all the
rods share the same photo pigment. They all have the same spectral sensitivity,
so we can't compare any activation levels across the rod population in order to in
order to decode wavelength, because the rods all share the same offset. Okay,
so let's dive into, um, the process of the photo transduction in the photo
receptor. So we started we've already seen the first step which is the absorption
of a photon by the retinal cofactor which calls this photo summarisation. And I
already mentioned that this is going to induce a conformational change in the
oxygen protein. And because it's a certain transmembrane protein, this will allow
it to interact with a heterotrophic G protein inside the photoreceptor outer
segment. And in the case of photoreceptors, that trimeric G protein has a special
name. It's called transduced in and. As usual, this interaction between the seven
transmembrane protein and the G protein is going to catalyse the exchange of
GDP to GTP and activate the hetero trimeric G protein. Hopefully, that's an
interaction you're already familiar with. So activate a transducer can then
activate an effector enzyme, which in the case of photoreceptors is called
phosphodiesterase. This yellow guy here and phosphodiesterase will then um,
catalyse the breakdown of cyclic GMP in the outer segment to GMP, which of
course results in a decrease in cyclic GMP concentration. the consequence of
that is that these cyclic nucleotide gated ion channels will close. So normally in
the dark there's a high level of cyclic GMP. It's generated by quite late cycles. It
gets these channels open and it allows cations to flow into the outer segment. So
this inward current in the dark is called the dark current. And it means that under
dark conditions photoreceptors are quite depolarised. They sit at around -30
millivolts. They're quite depolarised compared to a neurone. But when light is
instant on the phase receptor, and through this cascade, the cyclic GMP is broken
down and the channels close, the outer segment is going to hyper polarise. So
membrane potential. There's an undated potassium conductance and membrane
potential ahead of the reversal potential of potassium. And as a result we see
hyper polarisation of the membrane potential. So this is very important in
response to light photoreceptors hyper polarised. They do not depolarise
somewhat counter-intuitive And as a result of this hyper polarisation, they're
going to release less neurotransmitter. Less glutamate is released. This is
illustrated here. This is the pulse of light. This is a decrease in the inward current.
Notice the axis is the negative is decreasing. And we're going to see hyper
polarisation of the receptor and the release of less glutamate. Another important
thing to bear in mind is like all second messenger pathways this benefits from a
large amount of amplification. And as I've illustrated, here are some numbers.
You can see how the absorption of a single photon by one rhodopsin molecule
through this amplification cascade can result in a final change in membrane
potential of one millivolt, which is quite substantial, but given just one incident
photon on a rod photoreceptor. So this signal is something that has been
measured in some landmark studies. So this is a beautiful example of trying to
measure the responses of Individual photoreceptors, individual rods in I think it
was an unfortunate monkey whose retina was, um, donated for this experiment.
So in this experiment, the individual photoreceptors have sucked into this, um,
patch electrode, and it's exposed to very dim flashes of light at the time of these
dots. And hopefully what you can see are each of these dim flashes of light
causes a very brief hyper polarisation of the photoreceptor, measured using
perforated patch recording. Um, in some cases, this misses where the receptor
doesn't respond, and there's also occasionally a false positive. We get a little dip
even with no light flash. That's due to thermal isomerisation of retinal. But in
general, you can see that the photoreceptor is very good at reporting these very
dim light flashes, which are designed to explain receptors to just one photon
each time. Another important aspect of this response is that it's graded
according to the intensity of our of the light flash. So this is illustrated here now
for cones. So the time of this little blip, the cone is being exposed to flashes of
increasing brightness. And hopefully what you can see is this results in an
increasing amount of hyper polarisation as the flashes get brighter and brighter,
until eventually the response saturates. So this means that the cone is kind of an
analogue sensor, where the intensity of the light flash is converted into a graded
change in hyper polarisation, and therefore a graded change in glutamate
decrease onto downstream neurones. Um, with this type of recording technique,
you can also measure um, currents. So here's some current recordings are being
made. Um, in real time cones. You can see that under dark conditions there's an
inward current -30 ish pico amps. And in response to a light flash, that dark
current that we talked about is shut off as a cyclic nucleotide gated cation
channels close. You can see this decrease in the inward Inwood Current. And you
can also see that the dynamics of this, of these current changes in the
photoreceptors are quite different from rods and cones and cones have a much
faster response kinetics than rods. So we've sort of mentioned now over the
course of the last few slides, a number of different differences between rods and
cones, and they sort of captured on this slide to make things easier. So rods as I
mentioned, are very abundant in the retina. They're extremely sensitive. They're
about a thousand times more sensitive to light compared to cones. And they
mediate a vision at very low light levels known as topic vision. And they're
sensitive in part because they have very long outer segments containing tons of
discs and lots of photo pigment and show very high levels of amplification.
However, they all have the same type of opposition to the toxin, and so they
have the same shared spectral sensitivity, which results in achromatic vision.
The cones, on the other hand, have lower sensitivity. They only support vision at
of higher light intensities is no this topic vision. But there are three types of
cones with three different types of cone option, and as a result of this they
support colour vision. So averaging for time. Good. So now we've only touched
on the first cell in the retina the photo the photoreceptors. And we're now going
to have a look downstream of these cells some of these vertical pathways
through the retina for the remainder of this lecture. So. Downstream of the
photoreceptors these vertical pathways are going to be the first point that
contributes to some of this feature extraction and parallel processing that I
referred to at the beginning. And one very important distinction is that these
vertical pathways can be broken down into so-called on and off pathways that
kind of illustrate in very simple terms downstream of the cones in this slide. So
these on and off pathways sometimes cause some confusion. But if you pay
attention now you won't be confused. So the important aspect of these pathways
is they're named according to the change in light intensity, which is going to
evoke spiking in the pathway. So in the En pathway, cells are going to respond by
increasing spiking in response to an increase in light intensity i.e on whereas in
the off pathway cells are going to increase that spiking in response to a decrease
in light intensity so-called off response okay. Both pathways can modulate in
both directions. Right. So the on pathway where it spikes in response to the
increase in light intensity, a decrease in light intensity will cause a suppression of
spiking. We just get the opposite of response. And then off pathway which which
as we saw prefers light off. So it increases spiking when the intensity goes down.
If the intensity goes up. Spiking will be suppressed. So both pathways can
modulate bi directionally, but they have opposite preferences. The off pathway
prefers preferring, meaning it's going to spike more. A decrease in light intensity.
Whereas the On pathway is looking for an increase in light intensity. Okay.
Remember this. The key thing here is we're talking about changes in light
intensity. So these are increments or decrements in light intensity that the
pathways are interested in. Um the pathway is more complicated as we will see.
So these on and off pathways start at the level of the bipolar cells. All the phase
receptors as we've seen, have the same response to an increase in light
intensity, which is like hyper polarised and release less glutamate that we've
already seen. So this distinction between on and off is starting with our bipolar
cells. And in the mammalian retina. There's lots of different types of bipolar cell.
So they have different morphologies and um, different functions. Um, all of them
make connections with photoreceptors in the outer flexible layer, and then they
generate their they elaborate synaptic terminals here in the inner plexus form
layer, which in the case of cone bipolar cells will connect onto retinal ganglion
cells. There's a whole bunch of different types of cone bipolar cell. All of these
are cone bipolar cells and just one lonely Roger bipolar cell, which we'll see its
special properties. Uh, see? So why do we need so many types of bipolar cell?
You're probably wondering. Well, remember that in the cone system we have
three different types of cone. And they all contribute in various ways to on and
off pathways, which subdivides the number of channels in the retina to some
largish number. So it's quite complicated. But this key distinction that I
mentioned between on and off is always true. So the on pathways always
respond to an increase in light intensity with increased spiking. And the off
pathway does the opposite. An increase in light intensity will cause a decrease in
spiking. So now let's see exactly how this happens. By stepping through the on
and off pathways, starting with the cones, which is a slightly simpler case. So
that's why you need to pay special attention. So the photo receptors are shown
up here. These are the bipolar cells and these are the ganglion cells. And we're
going to imagine the response to an increase in light intensity. Um and this light
of course is first absorbed by the cone. So imagine there's an increase in light
intensity. We already know what's going to happen in the cones. Right. This is
going to cause the cell to hyper polarise and release less glutamate. So that
hyper polarisation is illustrated here. The key distinction between the on and off
pathways, um, is in the cone system results on this first synapse between the
photoreceptor and the bipolar cell. So on bipolar the cells expressing that
postsynaptic membrane, a specific glutamate receptor called MK six, which is
inhibitory. So this glutamate receptor acts on a cation conductance in the bipolar
cell to inhibit it. This means that when there's a decrease in glutamate release,
unless activation of mg R6, we're going to see a decrease in inhibition. It's a bit
like taking your foot off the brake is decrease in inhibition results in activation
and depolarisation of the bipolar cell. So you can see this is also known as a sign
inverting synapse. Because we've converted a negative the decrease in
glutamate release into a positive, which is the depolarisation of the bipolar cell
and the depolarised bipolar cell. Then in a more usual way, we'll release
neurotransmitter glutamate onto the downstream ganglion cell and cause it to
spike more. So you can follow that pathway here. Open polarisation of the
photoreceptor caused through the sign inverting synapse, the depolarisation of
the bipolar cell, and that was relayed to the ganglion cell. And then because
that's the spiking neurone, we see an increase in spike rate, okay. In the off
pathway the off bipolar is expressed a different type of glutamate receptor,
which looks a lot more like an Ampa receptor that you're probably familiar with.
So as a result, a decrease in glutamate release from the receptor will simply
cause less Ampa activation and therefore hyper polarisation of the off bipolar
cell. It will release less neurotransmitter onto the ganglion cell. And so spiking
rates decrease. That's illustrated here. So hopefully this is clear. The key
distinction in these on and off pathways right comes down to this synapse at
least in the cone system which is sign inverting in this case where we have this
inhibitory L6 glutamate receptor but its sign conserving in lost most cases where
we have a straightforward appetite receptor. Some people are nodding. Yeah. You
want me to go for it again? Or one person at least. Okay. So all so the difference
between these two pathways remembers starting at the bipolar cells, the cones
always being the same thing. So they're going to respond to an increase in light
intensity by hyper polarising and releasing less glutamate. So that's that's the
same across both pathways. However the on bipolar cell responds to that
decrease in neurotransmitter like depolarising because it has this inhibitory and
glucose six, which is now less activated by because glutamate concentration is
decreased. And so the cell depolarise activate this ganglion cells, we see more
spiking. Whereas on the off side that decrease in neurotransmitter simply results
in less activation of an AMP receptor, therefore less inward current into the polar
it will hyper polarise. Or at least less. Neurotransmitter. And so the ganglion cell
will spike glass. Okay, so. That's the cone on and off pathways. What about the
rod system. So as you will remember there's only one type of rod bipolar cell.
And it looks like a cone on bipolar. So it expresses m l6. And in response to an
increase in light intensity and less glutamate release, the rod bipolar will
depolarise. Now the interesting thing is that rod bipolar cells don't make direct
connections onto ganglion cells. Instead they're actually going to hijack the cone
pathway. And that the way they're going to do this is um, by means of our well,
it's our first example of lateral information flow in the retina. They hijack the
cone pathway, um, by way of an interneuron called an omicron's cell, which
extends lots of processes in the in the inner place the form layer. Here's the
console. Here's some pipe mounted rest and they're showing what they look like.
And what this alma principal does is it gets contacted by the rod bipolar and it's
in turn makes contacts with the presynaptic terminals of cone bipolar cells. And it
can do this in two ways. So in the on pathway the console makes electrical
synapses onto the presynaptic terminals of the cone on bipolar. So this means
that when the rod bipolar depolarise that depolarisation is propagated to this
presynaptic terminal resulting in more neurotransmitter release and therefore
excitation of the ganglion cell. However, in the off pathway, the American cell is
going to make a sign inverting glycine inhibitory synapse onto the presynaptic
terminal of off cone bipolar, which will hyper polarise this terminal, resulting in
less neurotransmitter release and as a result, a decrease in firing rate of the
ganglion cell. So there's sort of two modes that the cell can connect the rod
bipolar to the cone system. One is for an electrical synapse which propagates the
excitation right through. So we get an increase in spiking. And the other is by
sign inverting it through another inhibitory synapse which suppresses spiking.
Um, the very cool thing about this system is that it's actually the same American
cell that does both tasks. The very famous A2 American cell. And, um, you can
read more about the American cell and some of the selected reading. But the
way you can do this is because it has different layers of neuritis, some of which
are connect onto the on system to make electrical synapses, and a different kind
of layer of neuritis and the inner form layer, which I do this glycine allergic
transmission. So it's a very hard working neurone. Um, I think you can hopefully
appreciate it a little bit like the coin system. The secret to these on and off
responses comes down to either sign conserving or sign inverting synapses. But
in the case of the rod system, the critical sign ups is this one between ATM and
cell and the cone by polars. Whereas in the cone system the critical sign ups was
the first one. It was from the cone itself onto the bipolar cell. So this might all be
quite a lot to um, uh, remember, um, this table sort of summarises the difference
between the on and off pathways for both the cones and the rods. The key thing
to remember is that the difference between on and off responses starts at the
level of the bipolar cells. It depends on the presence of a sign inverting or sign
conserving synapse in the cone system. As we mentioned, it's the first sign ups
from the cone to the bipolar cell. One is expressed as R6, the other is an emperor
sceptre. But in the rod system, the rod bipolar doesn't make direct connections
onto ganglion cells. It uses this omicron's cell, and the omicron's cell makes
either a sign conserving or sign inverting synapse. Okay, um. Let's summarise.
So what you should have learned this morning is about some basic features of
the visual field and stereo and eye movements. We spent some time looking at
the process of transduction. You do need to know the details of the approach,
understand selection pathway and understand it completely. Um, particularly
knowing that in response to an increase in light intensity, the photoreceptors
hyper polarised. Um, we've talked a little bit about the, the mainly the
differences between rod and cone pathways and the different visual functions,
those two types of photoreceptor play. And then we've started to examine the
roles of the retina in neural computation, starting with these on and off
pathways. If you're wondering what the point of the on and off pathways is, then,
um, your, uh, questions hopefully will be answered this afternoon when we see
how they used to build the interesting response properties of retinal ganglion
cells and what that in turn, is useful for. So, um, that's all the, um, on the last
slide, I don't know if these slides are these slides on Moodle. Yes. Okay. So on the
last slide you can um see some some recommended readings, especially this one
if you want to do some uh, book chapter, uh, reading alongside the lecture
slides. Um, I will see you again, uh, for I think here. And we will start with, um, a
Moodle quiz to see if you, um, learned anything about the on and off pathways,
then see what they are used for and then have another Moodle quiz. Okay.