Striatal dopamine structures spontaneous behavior across multiple timescales

Abstract

Animals maneuver through the world by building elaborated, flexible sequences out of shorter, stereotyped actions. In the mammalian brain, monosynaptic and multi-synaptic circuits in cortico-striatal loops are thought to orchestrate the successful concatenation of actions into appropriate sequences depending on ethological context. We hypothesized that the release of neurochemical dopamine across multiple striatal structures regulates the probabilistic selection of actions in a sequence, given prior work demonstrating dopamine’s role in modulating behavioral variability and reinforcement in structured tasks. We recorded and manipulated dopamine release in the dorsolateral striatum (DLS) and found that persistent and fluctuating peaks in release contained both short- and long- timescale encodings of behavioral patterning variables during free behavior. Fast- timescale manipulations of DLS dopamine release demonstrated that it is causal for regulating behavioral choices. Manipulations of nucleus accumbens (NAc) dopamine release, however, did not have this causal effect. Finally, ventral dopamine circuits rely on intact DLS principal cell function to promote changes in behavioral choice. These results suggest a privileged role for dopamine in the DLS for organizing behavioral sequence formation during naturalistic behavior.