So what can tadpoles teach us about autism?
Well, our brains-- indeed all brains-- are made up
of specialized-- well, highly specialized brain cells
and they're called neurons.
And neurons have this amazing ability
to self assemble into highly organized neural circuits.
Now these neural circuits, they give rise our perceptions
and they dictate how we experience the world.
Now, when abnormalities occur in this circuit function
or in circuit form, well that could profoundly
affect how we experience, perceive and interact
with the world around us.
Oftentimes these circuit abnormalities well,
they present in the form of the behaviors
that we ascribe to neural developmental disorders,
like epilepsy or schizophrenia or even autism.
Animal models that lend themselves
to the study of the brain both developmentally
and functionally from different levels
and different perspectives well, they
can provide us insights into how human brain disorders arise.
One specific example of this is valproic acid.
The world over valproic acid is one
of the most commonly prescribed anti-seizure medications.
It's also often prescribed as a mood-stabilizing drug
for bipolars, as well as schizophrenics.
However, despite its utility as a medication,
it has known deleterious effects.
If a developing fetus is exposed to valproic acid
because the mother has to take valproic acid
to control her seizure history, this
causes some 12% 15% increase in the risk
that that child will be diagnosed
with a neurodevelopmental disorder.
Even more surprising is that of these children that
are prenatally exposed to valproic acid
and diagnosed with a neurodevelopmental disorder
well, they're ultimately diagnosed with autism spectrum
disorders.
Now, autism spectrum disorder, if you're not familiar,
is made up of what's known as the triad of impairments.
This is a decrease of socialization,
a decrease in communication, however an increased propensity
for repetitive or stereotype behaviors.
Now thus far, we as scientists, we
have been unable to understand how valproic acid is causing
these neurodevelopmental disorders.
And that's in part due to the fact
that we don't have an ethical way of accessing the developing
functional brain during pregnancy.
Now, in the Aizenman Lab here at Brown University,
we use tadpoles to study brain development, brain function
and brain disorders.
Now, what makes this model organism
such a useful model system particularly within this case
is that tadpole embryos develop very similarly
to human embryos.
Moreover, their brains, or nervous systems,
develop very similarly to human embryos
as well, or human brains as well.
This means that we can access the developing functional
circuits and we can look and test
how changes in circuit formation and circuit
function ultimately dictate changes in behavior.
So when we expose these developing tadpoles
to valproic acid, we find that the neural circuits
have significantly changed.
They become hyper-connected, they become hyper-excitable.
And somehow, the individual neurons that make up
those circuits well, they become less excitable.
Now, how do we test for socialization in tadpoles?
Well, tadpoles school very similarly
to how fish school and this is a social behavior.
So again, when we expose these tadpoles to valproic acid
and we measure their ability to school,
we find that they school abnormally,
meaning they have decreased ability to socialize.
So, what can we learn from tadpoles, particularly about
autism?
Well, we can learn three things.
One, we can use this animal model
to understand how valproic acid is causing
these neurodevelopmental disorders.
Two, we can use it to identify potential therapeutic targets
that we can manipulate in order to reverse and/or protect--
well, reverse the effects and/or protect the developing fetus
against the deleterious effects of valproic acid.
And three, and most importantly, is
that we can use these quote unquote
autistic tadpoles to identify whether neural developmental
disorders that arise from genetic or environmental risk
factors have the same sort of mechanisms
as valproic acid induced neurodevelopmental disorders.
And if we can find these conserved biological targets
well, that may be the key to unlocking the mystery that
is human brain disorders.
Thank you.
[APPLAUSE]