Primary Department Affiliation: Neurobiology
Primary Research Area: Learning,Memory,and Synaptic Palsticity
Ion Channels and Synaptic Function
Neurodevelopment and Developmental Disabilities
Synaptic Transmission, Presynaptic Properties of Single Synapses
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.
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