Role of the prefrontal cortex in behavioral modulation of basal forebrain activit

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DESCRIPTION (provided by applicant): The prefrontal cortex (PFC) is a crucial region involved in goal-directed behavior and top-down modulation of sensory processing. Although much work has been done to study task-related activity in the PFC, the principles underlying its functional organization remain unclear. Here I propose to investigate the intriguing possibility that the functional similarity between PFC neurons is closely related to their shared projection targets, using the PFC projection to the basal forebrain (BF) as a case in point. This pathway is thought to partly mediate PFC's top-down modulation of sensory processing, but this idea still lacks experimental support. Using state-of-the- art retrograde viral tracing techniques, I will firt perform a detailed anatomical characterization of the PFC-BF pathway. The next step will be to combine such techniques with two-photon calcium imaging in awake, behaving mice to identify BF- projecting cells in the PFC and measure their task-related activity, contrasting it with other cell populations within the region. The results will shed light on the functional organization of te PFC, as well as the circuit underpinnings of top-down modulation of sensory processing. Such knowledge is of great potential clinical relevance, given the involvement of PFC and BF in several neurological disorders, such as Alzheimer's disease, schizophrenia, and Parkinson's disease-related dementia.