Sensory processing impairments have been associated with a variety of neurodevelopmental disorders including autism spectrum disorder, Tourette syndrome, and attention-deficit/hyperactivity disorder, highlighting the need to understand its underlying neural mechanisms. Recent work has implicated basal ganglia’s involvement in mediating sensory-driven action, with the tail of striatum being of particular interest as it receives heavy inputs from various sensory regions including auditory cortex. Moreover, prefrontal inputs to the tail of striatum are known to regulate multimodal sensory selection through inhibition of distinct sensory thalamic regions. Furthermore, direct stimulation of SPNs in the tail of striatum is sufficient to bias auditory discrimination. Taken together, these data suggest that disruption of corticostriatal inputs to the tail of striatum may contribute to some of the sensorimotor impairments commonly associated with these disorders.

Copy number variation of genes encoding synaptic adhesion molecules, such as Neurexin1α (Νrxn1α), have been shown to confer a significantly increased risk for these neurodevelopmental disorders, however, the underlying neural dysfunctions associated with Νrxn1α loss remain to be fully understood. Recent findings in acute striatal slices have revealed that loss of Νrxn1α function results in decreased synaptic strength of medial prefrontal cortical inputs to the indirect pathway of the dorsal striatum. However, it remains to be determined whether corticostriatal deficits to the tail of striatum drive aberrant sensorimotor function.

To investigate sensory driven behavior and its underlying neural dynamics, we have developed a novel treadmill-based operant task for head-fixed mice which assesses responding to behaviorally relevant target sounds as well as behaviorally irrelevant distractors. Preliminary behavioral results suggest that mice with Νrxn1α mutation are more susceptible to distractor responding. Future experiments aim to describe the striatal population recruitment related to task performance in both Νrxn1α WT and Νrxn1α KO mice using in vivo and slice electrophysiological techniques. These findings will provide valuable insight into the neural pathology involved in neuropsychiatric and neurodevelopmental disorders while elucidating corticostriatal mechanisms involved in action control regulation.