Causal contributions of cell-type-specific circuits in the posterior dorsal striatum to auditory decision-making.

In the dorsal striatum (DS), the direct- and indirect-pathway striatal projection neurons (dSPNs and iSPNs) play crucial opposing roles in controlling actions. However, it remains unclear whether and how dSPNs and iSPNs provide distinct and specific contributions to decision-making, a process transforming sensory inputs to actions. Here, we perform causal interrogations on the roles of dSPNs and iSPNs in the posterior DS (pDS) in auditory-guided decision-making. Unilateral activation of dSPNs or iSPNs produces strong opposite drives to choice behaviors regardless of task difficulty. However, inactivation of dSPNs or iSPNs leads to pronounced choice bias preferentially in difficult trials, suggesting decision-specific contributions. Indeed, temporally specific iSPN activation within, but not outside, the decision period significantly biased choices. Finally, concurrent disinhibition of both pathways via inactivating parvalbumin (PV)-positive interneurons leads to contralateral bias primarily in difficult trials. These results reveal specific contributions by coordinated dSPN and iSPN activity to decision-making processes.