Christine Constantinople
NYU Center for Neural Science
New York University
Midbrain dopamine (DA) neurons are thought to be critical for reinforcement learning as well as motor control. A major outstanding question for the field is understanding how dopamine can satisfy these dual functions within the striatum, the input structure of the basal ganglia. I will describe our ongoing efforts to reconcile these dual functions of dopamine using rats performing a value-based decision-making task that includes reward- and movement-related events at distinct time points. Fiber photometry measurement of DA release in dorsomedial striatum revealed that only some event-aligned phasic DA signals were accompanied by movement, the amplitude of which predicted the vigor of upcoming contralateral movements. Phasic DA in the absence of movement signaled reward prediction errors (RPEs) and modulated rats’ behavior on subsequent trials. Electrophysiological recordings in the dorsomedial striatum showed trial-by-trial changes in firing rates at RPE-associated events, but not at movement-associated events. These data demonstrate DA-dependent plasticity and behavioral change following RPE on a trial-by-trial basis. To explain the dual role of DA in supporting movement and learning at distinct time points within a single trial, we hypothesized that acetylcholine’s (ACh) effect on striatal cell excitability may act as a gating mechanism. Fiber photometry measurement of ACh release in DMS revealed a unique pre-burst rise in ACh at movement initiation, and dips at RPE events, and optogenetic activation of ACh cells reliably initiated movements and impaired learning. These data suggest that the neuromodulator acetylcholine dynamically gates whether dopamine in the striatum is used for learning or moving on a moment-by-moment basis.
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