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

Striatum constitutes one of the key nodes of the decision-making circuit, with differing roles depending on the striatal localization and both direct and indirect pathway Striatal Projecting Neurons (d- and i-SPNs) populations. In a gambling task adapted to mice, we leveraged a computational characterization of the diversity in cognitive profiles to delve further into the striatal roles in decision-making. Individual decision-making profiles could be described as a combination between archetypal strategies (Optimizers, Risk-averse, Explorers). Such strategies reflected stable differences in the parameters generating decisions (sensitivity to reward magnitude, to risk or to punishment) derived from a reinforcement-learning fit of animal choices. Using a chemogenetic method, we found that dorsomedial striatum (DMS) neurons had the most significant impact on decision-making, while Nucleus accumbens (NAc) had a minor effect and dorsolateral striatum (DLS) had none. Specifically, d- SPNs reduce risk aversion by enhancing the perceived value of a risky choice in mice. On the other hand, i-SPNs amplified the importance of large gains, exerting opposite effects on mice depending on their decision-making profiles. Hence, we propose that striatal manipulations exert profile- dependent effects on choices because striatal subpopulations affect distinct parameters that interact to generate decisions.