Adaptation of sequential action benefits from timing variability related to lateral basal ganglia circuitry

Streamlined action sequences must remain flexible should stable contingencies in the environment change. By combining analyses of behavioral structure with a circuit-specific manipulation in mice, we report on a relationship between action timing variability and successful adaptation that relates to post-synaptic targets of primary motor cortical (M1) projections to dorsolateral striatum (DLS). In a two-lever instrumental task, mice formed successful action sequences by, first, establishing action scaffolds and, second, smoothly extending action duration to adapt to increased task requirements. Interruption of DLS neurons in M1 projection territories altered this process, evoking higher-rate actions that were more stereotyped in their timing, reducing opportunities for success. Based on evidence from neuronal tracing experiments, we propose that DLS neurons in M1 projection territories supply action timing variability to facilitate adaptation, a function that may involve additional downstream subcortical processing relating to collateralization of descending motor pathways to multiple basal ganglia centers.