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.

The posterior dorsal striatum (pDS) plays an essential role in sensory-guided decision-making. However, it remains unclear how the antagonizing direct- and indirect-pathway striatal projection neurons (dSPNs and iSPNs) work in concert to support action selection. Here, we employed deep-brain two-photon imaging to investigate pathway-specific single-neuron and population representations during an auditory-guided decision-making task. We found that the majority of pDS projection neurons predominantly encode choice information. Both dSPNs and iSPNs comprise divergent subpopulations of comparable sizes representing competing choices, rendering a multi-ensemble balance between the two pathways. Intriguingly, such ensemble balance displays a dynamic shift during the decision period: dSPNs show a significantly stronger preference for the contraversive choice than iSPNs. This dynamic shift is further manifested in the inter-neuronal coactivity and population trajectory divergence. Our results support a balance-shift model as a neuronal population mechanism coordinating the direct and indirect striatal pathways for eliciting selected actions during decision-making.

Sensory-guided decision-making is a vital brain function critically depending on the striatum, a key brain structure transforming sensorimotor information into actions. However, how the two opposing striatal pathways work in concert to select actions during decision-making remains controversial. Here, using cell-type specific two-photon imaging and optogenetic perturbations from the posterior dorsal striatum during decision-making behavior in mice, we uncover the population coding and causal mechanisms of the direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs) in decision-related action selection. Unexpected from prevailing models, we found that both dSPNs and iSPNs contain divergent subpopulations representing competing choices, and exhibit ensemble-level asymmetry: stronger contralateral dominance in dSPNs than in iSPNs. Such multi-ensemble competition/cooperation causally contributes to decision-related action selection, as supported by systematic optogenetic manipulations and verified by computational modeling. Our results unravel a multi-ensemble coordination mechanism in the striatum for action selection during decision-making.

The striatum comprises distinct types of neurons giving rise to the direct and indirect basal ganglia pathways and local circuits. A large amount of work has been focusing on cell-type specific striatal circuits in the context of movement control, proposing several models on their functional roles. But it remains to be elucidated how the cell-type specific striatal circuits contribute to decision-making behavior and whether the existing models apply. Here, we investigate the causal roles of the cell-type specific circuits in the posterior tail of the dorsal striatum (TS) of mice in an auditory-guided decision-making behavior. Transient unilateral activation of the direct- or indirect-pathway striatal spiny projection neurons (dSPNs or iSPNs) both biased decisions in opposite directions. These effects, however, were not due to a direct influence on movement, but was specific to the decision period preceding action execution. Optogenetic inactivation of dSPNs and iSPNs revealed their opposing causal contributions to decisions. At the local circuit level, simutaneous optical recording and manipulation of dSPNs and iSPNs revealed their antagnizing interactions. Inactivation of PV interneurons, a common inhibitory input to both dSPNs and iSPNs, facilitated contraversive choices, supporting a causal contribution of coordinated striatal circuits. Using a neural circuit model, we further demonstrated the computational implemenation of the causal circuit mechanism. Our results indicate that while the causal roles of the cell-type specific striatal circuits in decision-making largely agree with classic models in movement control, they show decision task-related specificity involving local circuit coordination.

Action selection during decision-making depends on the basal ganglia circuits that comprise the direct and indirect pathways known to oppositely control movement. However, the mechanism for coordinating these opponent pathways during decision-making remains unclear. We address this by employing deep-brain two-photon imaging and optogenetic manipulations of the direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs) in the posterior striatum during an auditory decision-making behavior. We show that while dSPNs and iSPNs play opposite causal roles during decision-making, each subtype contains divergent ensembles preferring different choices. The ensembles in dSPNs show stronger contralateral dominance than those in iSPNs manifested by higher-level activation and synchronization. Consistent with this asymmetrical contralateral dominance, optogenetic disinhibition of both pathways promoted contralateral choices. A computational model incorporating the striatal ensemble asymmetry recapitulated the causal behavioral effects. Our results uncover the asymmetry between opponent SPN ensembles as a circuit mechanism for action selection during decision-making.