Striatal indirect pathway mediates hesitation

Determining the best possible action in an uncertain situation is often challenging, and organisms frequently need extra time to deliberate. This pause in behavior in response to uncertainty – also known as hesitation – commonly occurs in many aspects of daily life, yet its neural circuits are poorly understood. Here we present the first experimental paradigm that reliably evokes hesitation in mice. Using cell-type specific electrophysiology and optogenetics, we show that indirect, but not direct, pathway spiny projection neurons specifically in the dorsomedial striatum mediate hesitation. These data indicate that the basal ganglia circuits controlling the pausing involved in cognitive processes like hesitation are distinct from those that control other types of behavioral inhibition, such as cue-induced stopping.