Nucleus accumbens and dorsal medial striatal dopamine and neural activity are essential for action sequence performance

Separable striatal circuits have unique functions in Pavlovian and instrumental behaviors but how these roles relate to performance of sequences of actions with and without associated cues is less clear. Here we tested whether dopamine release and neural activity more generally in three striatal subdomains are necessary for performance of an action chain leading to reward delivery. Male and female Long-Evans rats were trained to press a series of three spatially-distinct levers to receive reward. We assessed the contribution of neural activity or dopamine release within each striatal subdomain when progression through the action sequence was explicitly cued and in the absence of cues. Behavior in both task variations was substantially impacted following microinfusion of the dopamine antagonist, flupenthixol, into nucleus accumbens core (NAc) or dorsomedial striatum (DMS), with impairments in sequence timing and a strong impact on motivation after NAc flupenthixol. In contrast, after pharmacological inactivation to suppress overall activity, there was minimal impact on motivation, except within the uncued task after DMS inactivation. Inactivation of both NAc and DMS impaired sequence timing and led to sequence errors in the uncued, but not cued task. There was virtually no impact of dopamine antagonism or reversible inactivation of dorsolateral striatum on either cued or uncued action sequence completion. These results highlight an essential contribution of NAc and DMS dopamine systems in motivational and performance aspects of chains of actions, whether cued or internally generated, as well as the impact of intact NAc and DMS function for correct sequence performance.