abcs
|
SYNAPSES
A major focus of the lab is to understand
how the connections between neurons, the
synapses, work. It is known that when an
action potential invades a presynaptic
bouton it opens voltage-gated calcium
channels. This results in the local
elevation of calcium that causes synaptic
vesicles to fuse with the plasma membrane
and release their contents. The
resulting release of neurotransmitter
activates receptors on the postsynaptic cell
resulting in an electrical signal that
influences the firing of that cell. We
are examining the mechanisms that regulate
neurotransmiter release.
|
|
SHORT-TERM
SYNAPTIC PLASTICITY
Presynaptic forms of short-term synaptic
plasticity can reduce synaptic strength
for hundreds of milliseconds to seconds
(depression), or enhance it for hundreds
of milliseconds (facilitation) to minutes
(augmentation and post-tetanic
potentiation, PTP). In addition, synaptic
strength can be regulated on rapid
timescales by activating presynaptic
ionotropic receptors and metabotropic
receptors.
These forms of short-term
plasticity allow synapses and circuits to
perform computations, and proteins
involved in short-term synaptic plasticity
have been implicated in a variety of
neurological disorders. Chemical
messengers can also regulate
neurotransmitter release by activating
either ionotropic or metabotropic
receptors. A major goal of our research is
to determine the mechansisms and
functional consequences of short-term
synaptic plasticity.
|
|
|
|
CIRCUITS
It is important to consider the properties
of synapses in the context of a synaptic
circuits. We are studying sereral
simple circuits in the cerebellum and in the
thalamus. These studies focus on
feed-forward and feed-back inhibition. |
|
CLINICAL RELEVANCE
Dysfunctional synaptic plasticity has been
implicated in numerous brain disorders,
including depression, dementia, ataxia,
anxiety disorders and addiction. Our
research contributes to a basic
understanding of synaptic plasticity that
provides a foundation for understanding
these brain disorders. Cerebellar
studies
provide insight into Golgi cells and their
circuitry, which can give rise to ataxia.
Studies of retrograde signaling by
endocannabinoids provide insight into a
widespread phenomenon that is involved in
addiction and pain. Studies of the
connections between the basal ganglia and
the thalamus provide crucial information an
important circuit that is involved in
obsessive-compulsive disorder (OCD),
Tourette’s syndrome, and attention-deficit
hyperactivity disorder, Huntington’s and
Parkinson’s disease.
|
|
|
