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

First Author  Ferrigno SM Year  2026
Journal  Sci Adv Volume  12
Issue  31 Pages  eaeb5352
PubMed ID  42536750 Mgi Jnum  J:391214
Mgi Id  MGI:8398880 Doi  10.1126/sciadv.aeb5352
Citation  Ferrigno SM, et al. (2026) Indirect pathway neurons in the tail of the striatum regulate inhibitory control over sensory driven behavior. Sci Adv 12(31):eaeb5352
abstractText  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 Neurexin1alpha, 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.
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