Synapses
in the central nervous system have the ability to alter the amount
of neurotransmitter released within tens of milliseconds. This dynamic
quality of the synapse allows for the rapid integration of different
types of information. Our laboratory uses a mouse model of the dorsal
lateral geniculate nucleus to study the mechanisms of synaptic plasticity
important in the developing and mature thalamus. We take advantage
of a combination of tools, including electrophysiologic and calcium
imaging techniques, as well as genetically altered mouse strains.
One area of our research examines the factors important in the formation
and refinement of synaptic connections during development. We have
characterized the functional convergence of the retinogeniculate
synapse during development as multiple inputs are eliminated and
the remaining synaptic inputs strengthened. Using this normal developmental
sequence for comparison, we have begun to identify and characterize
the factors that mediate the refinement of the retinogeniculate
connection. We are taking advantage of mouse mutants and pharmacological
manipulations to dissect the roles of specific molecular cues and
neuronal electrical activity in synapse maturation. Another area
of research focuses on the decoding of firing patterns of retinal
ganglion cells into the output response of the thalamocortical relay
neurons. We are addressing several questions: (1) how do specific
retinal firing patterns influence synaptic strength? (2) how do
ascending neurotransmitter systems from the brainstem modulate the
strength of the retinogeniculate synapse? and (3) how do long term
changes in presynaptic activity alter the properties of the retinogeniculate
synapse?