Dopaminergic Control of the Explore-Exploit Tradeoff via Spiny Projection Neurons in the Striatum

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Project Summary In order to effectively make decisions, individuals must use their experiences to balance choices that have a known, positive outcome (exploitation) and choices that sample alternatives to better estimate the comparative value of the current selection (exploration). Altered regulation of these fundamental states may be central to executive function deficits apparent in neuropsychiatric disorders such as autism, obsessive compulsive disorder, Tourette’s syndrome and addiction. In order to study the neural mechanisms governing the balance between these two states, we generated novel 3-alternative choice task for mice. We will combine this operant behavior with cutting-edge viral, genetic and imaging tools to probe how dopamine, a neuromodulator that has a long history of association with neuropsychiatric disorders, regulates the expression of exploratory and exploitative behavioral states. In addition, we will perform 1-photon in vivo calcium imaging of spiny projection neuron subtypes in the striatum, a brain area known to govern decision-making and similarly associated with various neuropsychological disorders. This project builds off of a prominent hypothesis that suggests dopaminergic modulation of striatal activity governs action selection by conveying the value of decisions. The goal of this proposal is to provide me with training in cutting-edge experimental techniques such as 1-photon calcium imaging, viral-genetic technologies, dynamical models of decision-making, and computational data analysis. These techniques will allow me empirically test how dopamine and striatal neuron activity organize decision-making during exploratory and exploitative behavioral states. The Fuccillo Lab at the University of Pennsylvania has already demonstrated the ability to produce excellent research and provide premier training to its members, making it a great fit for this proposal. In addition, the proposed work will benefit greatly from all of the facilities and resources made available to researchers at the University of Pennsylvania.