Indirect pathway neurons in the tail of the striatum regulate inhibitory control over sensory driven behavior

Inhibitory control, the ability to withhold action in certain contexts, is behaviorally essential. Disrupted inhibitory control is linked to various neuropsychiatric symptoms, making it critical to understand the underlying neural basis. We examined how the tail of the striatum (TS), a major basal ganglia sensory hub, regulates actions to sensory stimuli. Mice performed an auditory Go/NoGo task, while we recorded TS neuron activity. Both spiny neuron subtypes were recruited during target and nontarget sounds, but nontarget sounds uniquely engaged persistent indirect pathway neuron activity. Temporarily silencing this activity increased errors to nontarget stimuli, indicating a role in suppressing inappropriate action. In mice deficient for Neurexin1α, a gene linked to ASD and ADHD, TS indirect pathway recruitment was reduced, and these mice demonstrated auditory-specific inhibitory control deficits that were ameliorated by boosting indirect pathway excitability. These findings highlight a subcortical target to potentially improve attentional and behavioral regulation in neurodevelopmental disorders.