We study the mechanisms underlying the processes of learning and memory, at the molecular, cellular and systems level. Our current focus is on the immediate-early gene Arc, which plays an essential role in memory consolidation. We have shown that efficient Arc translation requires coincident activation of the NMDA receptor and fear/reward signaling pathways. We have localized Arc protein to the nucleus, where it associates with PML bodies, sites of epigenetic transcription regulation, and with Tip60, a histone-acetyltransferase implicated in Alzheimer’s disease, suggesting that Arc mediates formation of long term memories through epigenetic regulation of gene expression. A second project investigates how information is processed, encoded and stored in networks formed by neurons growing in vitro, using a combination of optogenetics and multi-electrode array recording techniques. These experiments have demonstrated that generic cortical microcircuits have fading and hidden memory processes, and are able to process complex spatio-temporal information. This optogenetic MEA platform allows us to investigate the molecular and physiological basis of disorders in memory, cognition, and perception. These projects are supported by an in silico drug development program which identifies small molecules with efficacy at therapeutic targets identified by our research program.
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