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Much? It's a pleasure to be here and ah, especially for you to ah have given up such a glorious
afternoon to hear us speak today. What I want to tell you about is some of the work that's
been going on in the center for visual science. This is a group of about thirty two faculty
members that I ah direct ah here at the University of Rochester. Ah, we focus on all different
aspects of vision. I am only going to be able to tell you about a very narrow slice of ah
all the work that is going on in vision science here in Rochester. I've been at Rochester
for thirty two years and the reason I spent my entire scientific career here is because
Rochester offers some advantages that you can't find anywhere else as I am sure um almost
everybody in this aud this audience appreciates for different reasons. The reason I think
Rochester is so wonderful is we have this very close proximility proximity between our
engineering school and the school for medicine and dentistry. And that allows us to collaborate
on innovative science bid projects that you couldn't really do anywhere else on the planet
and I want to give you some examples of some of those collaborations today. Okay. So, the
brain. The human brain is a tantalizing mystery. We don't understand how it works. We've made
enormous progress in trying to understand how it works but major mysteries about how
the brain codes information and allows us to see and hear and feel and think are a remain
a a largely a major mystery. One of the main reasons why it's a mystery is because thus
brain con consists of maybe ten billion cells. And each of those cells on average communicates
with about ten thousand other cells. So in the lower right here, you see a an example
of the complexity that we have to deal with. The way we've been trying to chart through
this a this a tissue to try to understand how it works has largely been done with a
single micro electrode recording from one of those ten billion cells at a time. And
what's really needed are methods that allows us to look at large numbers of cells simultaneously
so that we can figure out how they're talking to each other. How are they how are these
circuits of different cell classes a intertwined in such a way as to generate the complexity
of thought they we all take for granted um every day of our lives. Well, the the tact
that we have been taking on this problem at Rochester is not to look at the brain per
say or at least this part of the brain but to look at a different part of the brain,
the retina, which resides inside your eyes. The retina is a part of the brain. It is part
of the central nervous system and it's simpler than the whole brain and offers some hope
that if we can understand how that circuit works will have some insight into the general
principles that the brain uses in order to compute stuff. So, here you can see an eye
and one of the nice advantages of working in the eye is that it has a natural window
that allows you to look at a part of the central nervous system directly. So, if we do a fly
through into this eye, you can see what I mean. Here's a one centimeter square and just
for scale, that's the retina you are looking at now or the retinal images cast. We've developed,
at Rochester at Technology to look at this retina in a way that no one has ever been
able to see it in the living eye before. Here is a very high magnification view of the retina
obtained with a conventional camera, commercial camera for taking pictures of the inside of
the eye at a scale which single cells ought to be visible. You can't see the single neurons
in the retina with this technology because the resolution isn't good enough. But we've
developed a camera based on technology borrowed from astronomy that they use for taking very
sharp pictures of of very faint stars and we can create a new view of the same structure
you you are looking at here that looks like this where we can now see all the rods and
cones, the photo receptors in the retina upon which the retinal images cast and that a provides
the first step, the first neural step in vision because these cells absorb light, convert
that light into an electrical signal that ultimately makes it to the brain. So the first
step in studying the a the retina in a novel way and understanding it's circuitry is this
unique capability we have here at Rochester to look at the retina in a living eye, non-invasively
at very high resolution. What we'd like to understand is, what is the code that the retina
uses to talk to the brain. The retina takes the retinal image, converts it into a set
of neural signals and those neural signals then go up to the brain where they are interpreted
and and processed further. What is that code that's being used to send signals from the
the retina to the brain? The problem in answering that question is the same problem I alluded
to on the onset. If you go poking around with a single electrode recording electrical currents
in the retina, you'll never get there. There one point two million optic nerve fibers,
output neurons, in each eye. We need a technology that allows us to look at many neurons simultaneously
if we are going to understand what that code is. Well fortunately, molecular biology is
in in the middle of a revolution. You probably have heard about this. Genetic engineering
is um making progress by leaps and bounds. We've um managed to sequence the human genome.
We now even have the capability to take a single cell of one species, remove the genetic
material, put in a a new set of genetic material and change the species of that cell. People
are beginning to talk about actually creating new life forms using this technology. It's
a little bit frightening but the possibilities for health care are enormous. So we're trying
to capitalize on that technology here in Rochester and those developments in order to understand
the circuitry of the retina and the way we do it is this. We make a very a a a simple
injection into the eye, you can see the eye here and the that green stuff there is some
of the fluid that we inject but it's not just quite as simple as that. It's a little cleverer
than that. What we're actually injecting is a virus into the eye. It's a virus that's
completely benign. It doesn't do anything harmful to the eye. It's in our bodies all
the time anyway. But what that virus, has been ah it has been modified in a way so that
it actually has the genetic machinery in it to make molecules that glow when their illuminated
with light. So what we can do is inject this virus into the ah eye and it um goes and infects
these cells that we wanta these output neurons that we want to study and they're shown ah
at the bottom of the slide here in this cross section of the retina, those those sort of
um purplish cells there are are the output neurons called the ganglion cells that send
the signals up to the brain and when we do this, the cells glow. So we get these beautiful
views of these ganglion cells, these output neurons, in in a living mouse eye by using
our high resolution imaging technology invented here in Rochester coupled with a this new
a a technology available through genetic engineering. So not only can we make these cells glow like
this, we we can also get them to glow in a way that's different depending on how active
the cells are. When they're more active, they send a larger signals to the brain, when they're
less active they're sending a weaker signals to the brain. So we can actually monitor optically,
using light, what these cells are telling the brain in real time, in a living mouse
while the mouse is seeing the world. So that's exciting, a exciting enough, and here is an
example I think ah from work, my collabators, Bill Merigan and Lu Yin, where a we 've a
circled a bunch of these cells and um we can go in and hear a hear some of them and we
can look at hundred of cells at one time. I am just showing you six and the important
thing to note here, is looking on the left of the slide, see how that image gets brighter
over time. It is getting brighter when we're del delivering a flash of light to the retina
so we're able again to optically monitor the signals that the retina is sending to the
brain while the eye eye of a living animal is seeing. Very exciting! But that's a basic
science application. You might be wondering, is there some medical application of this
technology that might help people. Is there some way that we can use this, for example,
to restore vision in the blind? Here's a cross section of the retina taken with a with a
light microscope showing all the different layers of that tissue, that part of the brain
as I mentioned, but now residing in the back of the eye. And you probably know there're
a host of diseases called um, generally retinal degenerations. With The one you're probably
most familiar with is macular degeneration, age related macular degeneration which some
of your relatives may well be suffering from. It's a very devastating disease. One in ten
people over 65 will be getting that ah will has that disease and we're expecting a doubling
in the prevalence of that disease ah in the next ah twenty years as a result of the aging
of our population. So this is a very important disease to try to find some way ah of fixing
and curing. So the idea is this, what if what happens in retinal degenerations, generally,
is the these, um the layer of cells there where where the red text is, those are the
photocepters the rods and cones and those are the cells that are damaged, destroyed
really, by macular degeneration or other kinds of retinal degenerations. Well, what if we
could somehow change the way the retina works and make those output neurons we've been studying,
what if we could make those intrinsically light sensitive. There not normally sensitive
to light directly, they just get electrical signals from the rods and cones. But what
if we could make the output neurons ah light sensitive. Well fortunately the same molecular
genetic engineering approach um, modified slightly, can be used to do that and the idea
is illustrated here where you're seeing a single neuron. We insert the genet genetic
machinery to make these cells intrinsically light sensitive, so these little green spots,
you see like measles all over that cell, those are little pores that are sensitive to light.
When you illuminate those pores, the neuron fires. So, where, as before, I showed you
a way that allows us to actually ah monitor cells in living eyes, now we have a way of
controlling them with this optogenetics approach. And just to show you that this actually has
some potential, here is an example. In a mouse, in which, um this mouse has not been treated
with this special injection and its blind. And you can see, it's trying to find the the
way out of this water maze, its swimming around. Mice don't like to swim and um very rarely
and almost just by chance will make it to the the the part of the maze where there's
light and that's that's the part that it will exit. But most of the time the mouse, unfortunately,
because its blind, flounds flounders around and can't make its way to the right place.
However, if you treat the animals with this a injection of this stuff called channel redopson,
the mouse immediately goes learns to immediately go to the right direction. So it regains sight,
a blind mice, mouse, has regained sight and is now able to solve this task. We're using
this method here at the University of Rochester. We have people who are very skilled, not only
at simple tasks, and understanding simple tasks like this that animals can do but we
can learn more about what animals can and cannot see that almost anyone or anyone else
in any other University um in the United States or in the world for that matter and we're
very excited about using this as a method for vision restoration a in the future in
cases of macular degeneration and so on. So I told you about a couple of different technologies
now that are available to transform the way that we understand how the brain works so
that we can look at large number of cells simultaneously and we can not only listen
to those cells and hear what messages they're conveying to their their neighbors, but we
can also control those cells so that we can send our own signals into the nervous system
if we want too. Now I'm sure all of you are familiar with um the sort of common actor
that you find in science fiction stories, where they be movies or um or books, the Cyborg.
Right where the Cyborg is a creature part human, part machine that allows a information
to flow from the machine to the human and back and forth. This technology, that I have
that we all have in our, most of us if your parents have bought you one, um in your um
in your pocket allows you to get a pretty large fraction the wealth of knowledge in
in in human kind at your fingertips already. I mean this is a remarkable technical innovation.
The next step logically, I'm not saying this will happen tomorrow, it won't. The next logical
step is to get that information directly into the nervous system. And what you might actually
be seeing in these developments I talked about today, of being able to communicate with neurons
in a two way communication, both listening and talking to neurons may actually be the
first ah baby steps toward the ability for machines and humans to ah to communicate directly
in the future. Now um, that that could be a a scary thought for some of you, it could
also be a very lim limbering thought if that technology is used in a wise and ethically
sound way and I think um the future is is very bright. This technology that I that I
talked about, the optogenetics method is already being used in in a animal models to to show
that you can control obsessive compulsion behavior, Parkinson's disease, depression
and an anxiety using these methods that use light as the basic way to communicate with
the nervous system. So we may have found the way to interface with the nervous system to
get computers and and the nervous system to talk together and I think it's it's a very
exciting future we have before us. Ah if you think I'm dreaming, what my father use to
say is, only the dreamer is awake. Thank you!