Previous studies indicate a central involvement of dopamine in the cortical-basal ganglia mechanisms of control and learning of motor and cognitive behaviors. However, a detailed understanding of how dopamine contributes to these processes and how these contributions are mediated by neurons in cortical-basal ganglia circuitry is lacking. Our proposal will investigate these issues by investigating the role of dopaminergic signaling within basal ganglia circuitry in modulating behavioral performance during a form of motor skill learning. We will test the hypothesis that low dopamine tone shifts behavioral performance and underlying neural activity towards a more variable and exploratory mode, while elevated dopamine tone promotes a shift towards a more stereotyped and stable mode. Songbirds are a particularly useful model system to investigate these questions. The songbird has a simplified but conserved cortical-basal ganglia circuit that is dedicated to a single, readily quantifiable behavior - song. The songbird dopamine system is also anatomically and physiologically conserved and is involved in social modulation of natural song behaviors. Adult songbirds can learn to change specific elements of song (the pitch of individual syllables) rapidly based on aversive reinforcement that is contingent on performance. This paradigm has proven to be effective in dissecting distinct stages of learning and their neural substrates, including initial acquisition, expression and consolidation of learning. The current proposal will build on these prior studies to investigate 1) behavioral consequences of manipulating dopamine tone for song performance during distinct stages of rapid song learning in adults, and 2) neurophysiological consequences of manipulating dopamine tone for the activity patterns of cortical-basal ganglia neurons during song performance. Results from these experiments will elucidate the role of dopamine in control and learning of complex behavior. These results will help inform a general understanding of how dopamine signaling within cortico-basal ganglia circuits contributes to behavior in both health and disease.

Public Health Relevance

Dopaminergic modulation of cortical-basal ganglia circuits plays a central role in normal motor and cognitive functions. Correspondingly, dysfunction of the dopaminergic system is thought to contribute to a variety of neurological and psychiatric disorders. The experiments in this proposal will provide insight into the role of dopamine in the control and learning of a complex motor skill. By studying how dopamine influences the progression of learning and underlying neural activity in the brain, we will gain insight into the normal functions of this neuromodulator and how they are disrupted in disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F02B-D (20))
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Chen, Daofen
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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