Striatal Control of Sensory-Driven Behavior and Its Relevance for Neuropsychiatric Disorders

Inhibitory control, or the ability to withhold an action in different situations, is behaviorally essential for daily life. Disruptions to different aspects of this process are associated with a wide range of neuropsychiatric symptoms, including impulsivity and attentional deficits, making it critical to understand the underlying neural basis. In this study, we examined how the tail of the striatum (TS), a major sensory hub within the basal ganglia, regulates actions in response to sensory stimuli. Mice performed an auditory Go/NoGo task while we recorded cell-specific activity from TS neurons to identify how distinct striatal pathways contribute to sound-driven behavior. Both major striatal neuron types were active during reward-related target sounds, whereas non-target stimuli preferentially engaged neurons of the indirect pathway. Temporarily silencing these neurons increased errors to non-target stimuli, indicating a role for these cells in suppressing inappropriate action. In mice deficient for the synaptic adhesion molecule Neurexin1α, a gene linked to several neuropsychiatric disorders including autism spectrum disorder, attention-deficit/hyperactivity disorder, Tourette syndrome, and schizophrenia, cortical recruitment of indirect pathway neurons in the TS was reduced, and these mice exhibited auditory-specific inhibitory control deficits. Preliminary experiments further suggest that enhancing synaptic excitability onto these neurons may be sufficient to ameliorate this behavioral deficit. Altogether, these findings identify a subcortical circuit that supports sensory-driven inhibitory control and highlights the TS as a potential target for improving attentional and behavioral regulation in neuropsychiatric disorders.

Author dc:creator

• Ferrigno, Sarah

Advisor dc:contributor.advisor

• Fuccillo, Marc, V.

• Neuroscience and Neurobiology

Language dc:language.iso

en

Repository record dc:identifier.uri

https://repository.upenn.edu/handle/20.500.14332/62352

OAI identifier oai:identifier

oai:repository.upenn.edu:20.500.14332/62352