Prefrontal cortex is critical for many high-order executive functions, including decision making, attention, and working memory. Dysfunctions in prefrontal executive control and decision making have been implicated in all aspects of addiction, including addiction establishment, expression, and relapse. To make decisions, prefrontal cortex requires information about current sensory and motor states, conveyed via long-range intracortical inputs, and information about reward states, conveyed via dopaminergic inputs. Indeed, dopamine is hypothesized to be a major regulator of intracortical connectivity, and is critical for models of associative learning in prefrontal circuits. Yet how this regulation occurs at the cellular level is unclear. The objective of this proposal is to identify cellular mechanisms by which dopamine regulates intracortical processing in prefrontal circuits, with particular focus on how dopamine can modulate learning rules at intracortical synaptic inputs. We will use a combination of electrophysiology, 2-photon imaging, and optogenetics to examine dopaminergic regulatory mechanisms, their recruitment by endogenous dopamine signaling, their time course, and dysfunction with drug use. Results of this study will provide insight into how PFC networks function normally and when challenged by drug use.

Public Health Relevance

This work focuses on how dopamine regulates the strength of connections between neurons in prefrontal cortical circuits. This is important because dysfunction in prefrontal dopamine signaling and its ability to regulate synaptic strength are thought to be major components to addiction and diseases co-morbid with addiction, including schizophrenia, bipolar disorder, and obsessive compulsive disorder.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
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Sorensen, Roger
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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