These are very unique times for brain research. The aperitif for the course will thus highlight the present “brain-excitements” worldwide. You will then become intimately acquainted with the operational principles of neuronal “life-ware” (synapses, neurons and the networks that they form) and consequently, on how neurons behave as computational microchips and how they plastically and constantly change - a process that underlies learning and memory. Recent heroic attempts to realistically simulate large cortical networks in the computer will be highlighted (e.g., “the Blue Brain Project”) and processes related to perception, cognition and emotions in the brain will be discussed. For dessert we will deliberate on the future of brain research, including the questions of “brain and art”, consciousness and free will. For more information see the course promo below and read “About the course.”
Optogenetics
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En provenance du cours de Hebrew University of Jerusalem
Synapses, Neurons and Brains
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À partir de la leçon
Brain Excitements for the 21st Century
Welcome to synapses, neurons and brains!
Rencontrer les enseignants
Idan SegevProfessor
Computational Neuroscience
So I want to go to the next frontier. The fourth frontier, which is
optogenetics. It's a recent one.
And the idea here, the general idea here is to develop again molecular genetic
tools, to be able to stain the cells. But in this case, not anatomically
necessarily, but to stain the cell or to, to implant probes into neurons, into
nerve cells that are sensitive to light. So that when I would shine light in a
particular wavelength onto this particular cell that we're manipulated to
become sensitive to light, then the cell will respond electrically.
We actually know of only one type of cells, nerve cells, in the brain that are
sensitive to light and this is our, our retina.
So when I see light, when I see a face, it means that the photons from the world
hit particular cell type, the receptors, the photoreceptors in the retina, and
these photoreceptors swallow, so to speak, the photons and generate
electrical activity in response. But this is only there.
But this means that there are molecules in our genes.
There are genes that can generate specific molecules that are sensitive to
light, and can transform, transform light into electrical activity.
So this is the magic. A group of scientists found the gene or
the molecule, the protein that you can embed into the cells that usually are not
sensitive to light in the brain. And then, when you shine light on this
brain, this group of cells respond electrically, although, usually they
don't, but now you made them sensitive to light.
So this is what is called optogenetics. You use genetic tools to make the cells
sensitive to [INAUDIBLE], to light. And we know today of two general types of
light activated cells. You can embed particular ion channel.
But, we'll talk a lot about ion channels later.
That when you shine blue light onto the cell, this ion channel opens and there is
current flow and the cell starts to fire. So this is one example here.
So, you record now from this cell, you don't stimulate the cell, you just
record, just to see what the cell responds to and you flash blue light,
blue light, blue light, blue light, onto the cell, onto this particular cell.
And you suddenly see the cell following the light start to fire.
So blue lights spike, blue lights spike. Okay?
So this is activating the cell, making it fire, spikes, we spoke about spike, just
using light. Okay, channelrhodopsins, that's a
fantastic way to selectively and particularly, when there is a light,
there will be a spike. You don't need to go into the cell
anymore. This is just to show you that there are
spikes. But we know today, that if this cell
contains this channel, this channel that you genetically manipulated it to be
there, this cell will fire with blue light.
The opposite thing happened when you put another type of, of protein there.
And in this case, you restrain, you block the activity of the cell.
In this case, with yellow light. So you shine a yellow light, this cell
usually fires. Let's say fire, fire, fire.
Then yellow light, yellow light, no firing.
You stop your light, fire, fire, fire. So in this case, the yellow light stops
the cell from firing and this what makes me, what, what I can do with it is now to
manipulate, as I want from the outside. If I have this genetic manipulation, I
can activate a group of cells, make them fire or I can stop a group of cells, stop
them from firing. And why this is so important?
Because, this means that I will be able to detect the group of cells that may be
responsible for a given, let's say, behavior or instead of stimulating them
with all these electrodes that I mentioned before, I will be able
hopefully to stimulate from the outside and maybe repair the network.
Or maybe activate the network to make the, the, the animal move or maybe there
is other activity in a particular region. I can calm down this activity using the
yellow light. So I can now start to control in a very
particular region, not in general brain. Just particular region or particular cell
type. I can manipulate it very, very, very
specifically. I want to show you a movie using this
technology of manipulating, so to speak, the behavior of a mouse.
So whenever there would be blue light, blue light, a group of cells will be
activated and this group of cells will, so to speak, force the mouse to drink.
And when this group of cells are not being activated, the mouse will be free
to do whatever he wants. So, here is the movie.
This is from Janelia Farm from Karel Svoboda.
So here is the mouse, running freely, but this is the optical probe that inject
this light. Notice that whenever there is blue light,
it doesn't see the blue light. Whenever there is a blue light, is going
to drink or eat from the left dish, and when there is no stimulus, he can do
whatever he want. But whenever there is blue light,
whenever there is blue light, he goes there.
He has been trained to go there, he must go there, because a stimulated group of
cells and he now really is controlled, so to speak, by this group of cells.
So whenever there is blue light into his brain, not, not what you see.
This is, by the way, done in dark or so, so so, he doesn't see the light.
It's only for you. So this is optogenetics.
It's a very, very new technique. Very, very powerful.
We really put a lot of hope into this technology, because it, it may, for the
first time ever, in the living behaving animal, we maybe able to induce a given
behavior or control compulsive behavior or maybe control Parkinson or other
diseases. Of course, the issue is whether we can
use it in humans, and this is ethical issues with society will have to decide,
but the technology is there. The decision whether to go into humans
with it is a decision that the society should do.
So we are developing methods that are very useful for research.
Whether they will be useful for clinical aspect, that's a decision of society not
of scientists. But I wanted to show you the technology.
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