Disrupted activity-mediated regulation of glutamatergic synapses have been implicated in a wide variety of neurological dysfunctions. We are trying to understand this plasticity and how the brain down-regulates it in order to modulate synapse function effectively and develop mechanism based treatments for these crippling disorders. We use time lapse imaging/deconvolution microscopy to dissect the role of synaptic signaling in the sprouting and structural stability of axons and dendrites of hardy Xenopus visual neurons in tissue culture. Perforated patch clamping from these cells, as well as techniques for patterning their substrates and therefore their connectivity, allow us to monitor and modulate the functional synaptic interactions underlying structural change. However, our major focus is on the intact rodent visual pathway. We have found that the maturation of glutamate function in the superior colliculus lateral geniculate nucleus and visual cortex is closely tied to changes in the activity of the developing retina. Use of mice mutant in synapse associated molecules, chronic application of glutamate receptor antagonists or agonists to the retina, the superior collciulus and visual cortex of mice and rats, combined with biochemical physiological, immunocytochemical and confocal/deconvolution microscopy are allowing us to detect the circuit and the molecular determinants of synaptic maturation and glutamatergic function in this pathway.
Affiliate Member, Picower
Center for Learning and Memory Professor, Departments of Biology and Brain
and Cognitive Sciences
Investigator, McGovern Institute for Brain Research