The role of striatum in controlling waiting during reactive and self-timed behaviors.

Abstract

The ability to wait before responding is crucial for many cognitive functions, including reaction time tasks, where one must resist premature actions before the stimulus and respond quickly once the stimulus is presented. However, the brain regions governing waiting remain unclear. Using localized excitotoxic lesions, we investigated the roles of the motor cortex (MO) and sensorimotor dorsolateral striatum (DLS) in male rats performing a conditioned lever release task with variable delays. Neural activity in both MO and DLS showed similar firing patterns during waiting and responding periods. However, only bilateral DLS lesions caused a sustained increase in premature (anticipatory) responses, whereas bilateral MO lesions primarily prolonged reaction times. In a self-timing version of the task, where rats held a lever for a fixed delay before release, DLS lesions caused a leftward shift in response timing, leading to persistently greater premature responses. These waiting deficits were accompanied by reduced motor vigor, such as slower reward-orienting locomotion. Our findings underscore the critical role of the sensorimotor striatum in regulating waiting behavior in timing-related behaviors.Significant Statement Waiting is essential for the temporal control of actions, as many cognitive behaviors-whether stimulus-driven or internally planned-require withholding a response until the appropriate time. However, the neural substrates of waiting remain less understood. Using targeted lesions, we identified the dorsolateral striatum as a crucial region for waiting in both reaction time and self-timing tasks. Lesions in this area caused a persistent increase in premature responses across tasks. In contrast, motor cortex lesions, despite its neurons showing similar activity patterns to the striatum during waiting, did not result in a lasting increase in premature responses; instead, they led to a long-term increase in reaction time.