TY - JOUR T1 - Action sequence dynamics rely on accessory hyperdirect pathway-related targets in the striatum JF - bioRxiv DO - 10.1101/2022.03.28.486040 SP - 2022.03.28.486040 AU - Lachlan A. Ferguson AU - Miriam Matamales AU - Bernard W. Balleine AU - Jesus Bertran-Gonzalez Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/03/29/2022.03.28.486040.abstract N2 - Performing several actions in swift succession is often necessary to exploit known contingencies in the environment. However, after a change in the contingency rules, the ability to appropriately adapt rapid action sequences must be procured for continued success. By combining analyses of behavioural microstructure with circuit-specific tracing in mice, we report on a relationship between action timing-variability and successful adaptation that relies on post-synaptic targets of primary motor cortical (M1) projections to dorsolateral striatum (DLS). We found that M1 hyperdirect pathway projections to the STN also send dense axonal collaterals to external globus pallidus and dorsal striatum, with the highest synaptic volumes found in the DLS. Specific interruption of the M1→DLS circuit reduced the proportion of successful sequences while speeding-up and reducing action timing-variability, revealing a role for M1→DLS circuitry in setting the exploration/exploitation balance that is required for adaptively guiding the timing and success of instrumental action.Competing Interest StatementThe authors have declared no competing interest. ER -