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.

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The prefrontal cortex is a crucial region involved in controlling goal-directed behavior. Consistent with this function, it is believed to play a key role in modulating how early cortical regions process sensory stimuli coming from the periphery. However, the neuronal circuits implementing this function remain poorly understood. Using state- of-the-art viral tracing and single neuron imaging techniques in behaving mice, this project will investigate task-related activity properties of neurons in the prefrontal cortex that project o the basal forebrain, another region involved in top-down modulation of sensory processing. The results are expected to reveal some of the general principles underlying the functional organization of the prefrontal cortex. Such knowledge is of great potential clinical relevance, given the involvement of this cortical region and of the basal forebrain in several neurological disorders, such as attention deficit disorder, schizophrenia, Alzheimer's disease, and Parkinson's disease-related dementia.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F02B-D (20))
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Babcock, Debra J
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University of California Berkeley
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Harrison, Thomas C; Pinto, Lucas; Brock, Julien R et al. (2016) Calcium Imaging of Basal Forebrain Activity during Innate and Learned Behaviors. Front Neural Circuits 10:36
Cox, Julia; Pinto, Lucas; Dan, Yang (2016) Calcium imaging of sleep-wake related neuronal activity in the dorsal pons. Nat Commun 7:10763
Pinto, Lucas; Dan, Yang (2015) Cell-Type-Specific Activity in Prefrontal Cortex during Goal-Directed Behavior. Neuron 87:437-50
Pinto, Lucas; Goard, Michael J; Estandian, Daniel et al. (2013) Fast modulation of visual perception by basal forebrain cholinergic neurons. Nat Neurosci 16:1857-63