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Hi, my name is David Linden and I'm a professor of neuroscience
at the Johns Hopkins University School of Medicine.
My lab studies how the brain repairs itself after injury.
To demonstrate how this happens, let's go to the toy box.
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We'll start out by making a model of nerve cells inthe brain out of Play Doh.
And we'll use another color Play-Doh to make a second neuron.
So in neurons in the brain information comes in through
the dendrites it flows through the cell body and
out through the axon.
So all these pieces have to be intact in order for
these nerve cells in the brain to function, but
what happens if there's damage?
We'll take from the tool box our letter opener.
And imagine that a stroke or a penetrating brain injury or
a concussion has caused damage that has severed this blue axon.
And then this severed bit, this end, will die away.
Then what you would hope would happen to recover function
is that there could be growth from this cut end that
would ultimately restore signaling in the axon and
restore brain function.
In other parts of the body, the cut end of the axon can indeed
grow back in this fashion.
But in the brain and the spinal cord,
it's been thought up until now that this never occurs.
What happens instead is that when an axon is
severed and the end degenerates,
there's a compensatory process that happens.
The neighboring neuron grows and
it sprouts an axon into the location,
the territory, that the blue axon used to occupy.
So this is the dogma, this is what's in all the textbooks.
It's thought that in the brain and
the central nervous system that the severed ends of axons can't
regenerate and this limits recovery of functions.
What my lab discovered using genetically modified mice
is that there are one particular group
of nerve cells within the brain, and these are nerve cells that
use the neurotransmitter called serotonin.
And the serotonin using neurons actually can,
very slowly, add little bits of axon onto their cut ends and
regenerate and rewire the brain.
And not only that, but we know that this regenerated bit
of axon is actually functional,
cuz we can measure the release of serotonin from the end where
it talks to other neurons in the brain.
Then what is it about the serotonin neuron that's special?
We know that in the tissue that
surrounds these nerve cells, there are chemical stop signals,
which we are going to indicate with this stop sign here.
And so this non serotonin neuron,
it can see the stop signals and when it's been cut,
it won't regenerate from its cut end at all.
To illustrate why the non serotonin neuron here in orange
sees the stop signal and therefore fails to regenerate,
let's go with the toy box and get our very fashionable friend
Ken and take his glasses and place them on the orange neuron.
And this indicates that this non serotonin neuron can see these
stop signals in the matrix of tissue.
Because this neuron can see these stop signals,
then it will not regenerate and it will not grow. However.
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The serotonin neuron, when it's been severed by injury,
it can't see the stop signals, so it will grow, and grow,
and grow, as if the stop signals aren't even there regenerating
the axon and helping to recover function after injury.
So this idea that the serotonin neurons can regenerate the axons
because they can't see the stop signals, it's just a theory.
We don't have any experimental proof of that.
We're in the process of testing that idea and
there's another notion.
So, one possibility is that the serotonin neuron can regenerate
because it has a big motor, indicated here by this nice toy,
that drives the serotonin axon through the stop signals,
through scar tissue that has formed in the brain and powers
it past all these problems in order to allow it to regenerate.
However, the non-serotonin neuron has a much
smaller motor, and so its motor, indicated here,
is insufficient to allow it to grow past.
And in truth,
these two classes of explanation could both be right.
It could be that serotonin neurons are special and
can regenerate both because they can't see stop signals and
also, because they have a large cellular motor
driving the regenerative process compared to
non-serotonin neurons.
Our hope is that when we identify the molecules that
correspond to the large engine or the lack of glasses in
the serotonin neurons, those molecules that allow these
neurons to regenerate while others can't,
that we will be able to use this insight to develop therapies,
drugs or antibodies that we can give to people after they've
sustained an injury to the brain and spinal cord, and
will allow them to them recover function more fully.
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