Cortico-limbic circuits for learning and memory

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The main objective of this NSERC-funded research project is to extend our understanding of the neural mechanisms by which newly learned behaviours are instantiated into long-term memories. Using a small 'interference peptide' (patent-pending), we are able to block the internalization of the AMPA class of ionotropic glutamate receptors and thereby block the final step required for a form of synaptic plasticity called Long-term Potentation (LTD.) We use this molecular tool in conjunction with sophisticated and behavioural tests to assess the role of synaptic plasticity in specific aspects of learning and memory, several of which we have refined in our recent studies. This research program will build on recent success in linking LTD to processes responsible for response flexibility and extinction of previously acquired memory. Following initial experiments in which the drugs are injected via the intravenous route, and selective memory disruption achieved in a specific behavioural test, subsequent experiments will attempt to localize the neural structure(s) in which a disruption of LTD reproduces the effects observed with systemic drug administration. With the advent of these new tools for manipulating LTD in the brain, we can now examine directly the functional effects of 'depotentiation" of LTP, by induction of LTD, on our brain-stimulation signal detection procedure. Our working hypothesis maintains that enhanced signal detection following LTP will be reversed by an 'LTD' stimulation protocol and that this effect can be blocked by administration of our 'interference peptide'. This project has important theoretical implication and should provide new insights into synaptic plasticity and information processing in brain.