Direct and indirect striatal projecting neurons exert strategy-dependent effects on decision-making.

The striatum plays a key role in decision-making, with its effects varying with anatomical location and direct and indirect pathway striatal projecting neuron (d- and iSPN) populations. Using a mouse gambling task with a reinforcement-learning model, we described individual decision-making profiles as a combination of three archetypal strategies: Optimizers, Risk-averse, and Explorers. These strategies reflected stable differences in the parameters generating decisions (sensitivity to the reward magnitude, to risk, or to punishment) derived from a reinforcement-learning model of animal choice. Chemogenetic manipulation showed that dorsomedial striatum (DMS) neurons substantially affect decision-making, while the nucleus accumbens (NAc) and dorsolateral striatum neurons (DLS) have lesser or no effects, respectively. Specifically, DMS dSPNs decrease risk aversion by increasing the perceived value of risky choices, while DMS iSPNs emphasize large gains, affecting decisions depending on decision-making profiles. Hence, we propose that striatal populations from different subregions influence distinct decision-making parameters, leading to profile-dependent choices.