Research Focus:
Synaptic Transmission, Presynaptic Properties of
Single Synapses
Research
Interests:
My research program uses electrophysiological approaches to study
synaptic transmission and regulation of presynaptic properties at synapses
in the central nervous system. Synapses in the central nervous system are
unreliable in that they release a vesicle of neurotransmitter only a small
fraction of the time they receive action potential input. The probability
of neurotransmitter release is history dependent, resulting in dynamic
modulation of synaptic strength by the timing of stimulation, a phenomenon
called short-term plasticity. Short-term plasticity is important for
information processing in the brain. In hippocampus, a region of the brain
involved in learning and memory, short-term plasticity is a cellular
correlate of short-term memory. Using hippocampal brain slices and
cultured hippocampal neurons from rodents, my lab studies the presynaptic
properties of single synapses and the regulation of presynaptic vesicle
release probability. There are currently three major projects under
investigation in my lab.
We are studying the effects of developmental regulation on presynaptic
function in neonatal hippocampus. Using electrophysiological recordings
from single synapses and populations of synapses in hippocampal slices,
along with pharmacological techniques, we are investigating the
developmental changes in synaptic release probability and short-term
plasticity that occur in the hippocampus during normal postnatal
development. This is important to understanding the formation of normal
neural circuitry, which occurs postnatally and depends upon synaptic
strength and dynamics. These experiments pave the way for future studies
to look for abnormalities in the development and presynaptic properties of
hippocampal synapses in animal disease models such as Down Syndrome, fetal
alcohol syndrome, and other causes of mental retardation.
In a second project, we are investigating the differences in
presynaptic properties of excitatory synapses onto excitatory cells vs.
inhibitory cells in hippocampus. Although short-term plasticity is caused
by presynaptic changes in neurotransmitter release, it is influenced by
the identity of the postsynaptic cell. We are investigating the cellular
mechanisms of the difference between these synapses, as well as the
importance of short-term plasticity in regulating the balance between
inhibition and excitation in hippocampus.
Since the hippocampus is highly susceptible to epilepsy, this
balance will be critical to normal hippocampal function.
In a third project, we are studying synaptogenesis and the
physiological properties of newly formed synapses in cultured hippocampal
neurons. Synaptic properties depend both upon the developmental stage and
the type of the postsynaptic neuron. The
mechanism is not known by which these factors influence synaptic
properties and neurotransmitter release. Using immunochemistry and
fluorescence microscopy, pharmacology, molecular biology, and
electrophysiology, we are investigating the formation and properties of
nascent synapses, as well as factors that affect synaptic maturation.
