Our laboratory studies synaptic plasticity in the mammalian central nervous system. We use a combination of tools, including electrophysiological and imaging techniques, as well as genetically altered mouse strains, to examine the regulation of synaptic function of the visual system.
One area of our research focuses on synaptic mechanisms and the decoding of firing patterns of retinal ganglion cells into the output response of the thalamocortical relay neurons. Using a brain slice preparation of the mouse lateral geniculate nucleus (LGN), we are addressing several questions: (1) how do specific retinal firing patterns influence synaptic strength through presynaptic and postsynaptic mechanisms, (2) how do ascending neurotransmitter systems from the brainstem alter the strength of the retinogeniculate synapse, and (3) how do long term changes in presynaptic activity alter the properties of the retinogeniculate synapse.
Another area of research examines the factors important in the formation and refinement of synaptic connections during development. We have characterized, using electrophysiological techniques, the convergence of the retinogeniculate synapse during development as multiple inputs are eliminated and the remaining synaptic inputs strengthened. In addition, we have uncovered a vision-dependent critical period at this synapse during which connections can be re-wired late in development. To identify and characterize the factors that mediate the different phases of remodeling of the retinogeniculate synapse, we are taking advantage of mouse mutants and pharmacological manipulations to dissect the roles of specific molecular cues. Using retinal explants co-cultured with thalamic neurons, we also plan to develop an in vitro system that recapitulates some of the developmental processes observed in vivo. This in vitro system will provide greater ease in manipulating gene expression, thus allowing us to identify novel molecules and factors important in the synapse remodeling.
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References:
Seeburg DP, Liu X and Chen C. (2004). Frequency-Dependent Modulation of Retinogeniculate Transmission by Serotonin. J. Neurosci. 24:10950-10962. Hooks BM and Chen C. (2006). A Model for Synaptic Refinement in Visual Thalamus. In: Guido W et al, eds. Development and Plasticity in Sensory Thalamus and Cortex. Kluwer Academic/Plenum Publishers.
Hooks BM and Chen C. (2006). Distinct Roles for Spontaneous and Visual Activity in Remodeling of the Retinogeniculate Synapse, Neuron 52:281-291.
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