The basal ganglia (BG) are critical for action selection and instrumental learning. Maladaptive learning in the BG circuits are known to result in behavior that persist despite harmful and aversive consequences. To understand the compulsive nature of such actions and their tendency for relapse, it is critical to elucidate the circuit mechanisms for the acquisition, reinforcement, and automatization of learned actions. Recent results from our lab showed that the BG are not used to select actions in an all-or-none fashion, as traditionally believed, but are necessary for the continuous generation of movement kinematics in voluntary behavior. These results suggest a new conceptual framework for understanding instrumental learning, allowing continuous quantification of performance as learning occurs and the effect of reinforcement. This proposal aims to determine the role of the BG in instrumental learning by combining wireless in vivo electrophysiology, optogenetics, 3D motion capture, and behavioral assays from the instrumental conditioning paradigm in freely moving mice. We will quantify continuous neural and behavioral dynamics during instrumental learning, habit formation, extinction, and reinstatement. We will also examine the contributions of the dopaminergic reinforcement signal. The proposed studies will elucidate how specific outcome and contingency representations can recruit instrumental action controllers in the BG. We will manipulate and record from specific BG circuits during initial instrumental learning and habit formation. Results from proposed studies will not only shed light on instrumental learning and reinforcement, but also lead to quantitative characterization of traditional categories such as goal-directed actions and stimulus-driven habits. They have important implications for our understanding of addiction, which involve maladaptive learning in the same neural circuits.
The same basal ganglia circuits mediating instrumental learning and habit formation are usurped by drugs of abuse in drug addiction. The proposed studies can have crucial implications for our understanding of drug addiction, and lead to development of targeted treatments for the development of compulsive drug seeking behavior as well as relapse.
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| O'Hare, Justin K; Li, Haofang; Kim, Namsoo et al. (2017) Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior. Elife 6: |
| Pappas, Andrea L; Bey, Alexandra L; Wang, Xiaoming et al. (2017) Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers. JCI Insight 2: |
