From avoidance to new action: the multifaceted role of the striatal indirect pathway

A hallmark of optimal reinforcement learning is that an agent learns to avoid actions that lead to negative outcomes while still exploring alternative actions that could lead to better outcomes. Although the basal ganglia have been hypothesized to contribute to this computation, the mechanisms by which they do so are still unclear. Here, we focus on the function of the striatal indirect pathway and propose that it is regulated by a synaptic plasticity rule that allows an animal to avoid actions that lead to suboptimal outcomes. We consider current theories of striatal indirect pathway function in light of recent experimental findings and discuss studies that suggest that indirect pathway activity is potentiated by the suppression of dopamine release in the striatum. Furthermore, we highlight recent studies showing that activation of the indirect pathway can trigger an action, allowing animals to explore new actions while suppressing suboptimal actions. We show how our framework can reconcile previously conflicting results regarding the indirect pathway and suggest experiments for future investigation. The functional roles of the striatal indirect pathway remain unclear. In this Perspective, Lee and Sabatini propose that a three-factor learning rule governs the activity of indirect striatal projection neurons, contributing to the learnt avoidance of actions with negative outcomes and the transition to alternative actions.