Ensemble Recording in Corticostriatal Pathways During Procedural Learning

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DESCRIPTION (provided by applicant): Mounting evidence indicates that procedural learning and habit formation require a restructuring of neural activity patterns in anatomical loops connecting the cortex with the striatum of the basal ganglia. Yet remarkably little is known about where and how these critical activity changes take place. This is a pressing issue for modern research and the broad goal of my proposed work. Technological advancements have now made it possible to record or silence the activity of large populations of neurons in spatially segregated brain areas at the same time. Harnessing these new tools, I will first simultaneously evaluate neural activity in cortex sites (infralimbic and premotor) and striatum sites (dorsolateral striatum) identified in brain lesion studies as critical nodes in the larger brain network for habit formation as rats are extensively trained on a maze task. This will allow me, for the first time, to track the restructuring of neural activity that encodes procedural learning and habits in both cortex and striatum, as well as evaluate the flow of information within corticostriatal loops as learning progresses. I will subsequently incorporate new gene-based methods to silence the activity of one habit site (in the infralimbic cortex), a procedure that is known to block habit-based behaviors, while simultaneously recording from neurons in another (in the dorsolateral striatum). In this way, I can evaluate how neural activity patterns that emerge with habit formation become delayed or obstructed when vital pathways of the cortex- basal ganglia are 'short circuited'. Finally, throughout the proposed I will incorporate anatomical tracing techniques to identify crucial circuit connections for learning-related plasticity within these sites, and will also include tests of behavioral sensitivity to reward value at different learning stages to evaluate the transition of behavior from 'goal-directed' or 'habitual' as formally defined. This research will use state-of-the art genetic and physiology techniques to identify the critical patterns of activity that emerge in the cortex and basal ganglia when a skill is learned and becomes a habit with practice. Understanding the brain basis of normal habit learning will be key to understanding how abnormalites of brain activity contribute to behavioral disabilities (e.g. in Parkinson's and Huntington's Disease) and compulsions (e.g., in drug addiction and obsessive-compulsive spectrum disorders).