SEMANTIC ACTION ANNOTATION REVEALS CONTROL OF OROFACIAL STEREOTYPIES BY THE VENTROLATERAL STRIATUM

Repeated exposure to CNS-active drugs, including psychostimulants, is well documented to induce involuntary motor behaviors such as stereotypies and dyskinesias, which frequently manifest in the orofacial domain. To study the circuit basis of orofacial stereotypies in freely-behaving mice, we developed an AI-based approach for automation of semantic action annotation (STEREO), with which we quantified the behavior of mice following repeated exposure to high dose cocaine. Repeated cocaine exposure gradually restricts the behavioral repertoire of mice towards repetitive prolonged bouts of surface licking, at the expense of other actions. These bouts were associated with transient elevations in the activity of iSPNs and dSPNs in the ventrolateral aspect of the dorsal striatum (VLS), and were abolished by optogenetic stimulation of VLS iSPNs, reverting mice to exploratory locomotion. Addressing whether VLS activity was sufficient to promote orofacial stereotypies, we optogenetically stimulated VLS dSPNs, observing a behavioral phenotype that mimicked cocaine-induced orofacial stereotypies. These results were further supported by chemogenetic modulation of VLS iSPN and dSPN activity during cocaine exposure. Finally, we queried the encoding and control of natural orofacial actions (ie body licking and grooming) by the VLS, and observed similar patterns of activity and iSPN control over self-directed licking induced by a sucrose splash. Our study reveals absolute control over orofacial actions by the VLS, and introduces an approach, broadly applicable across neuroscience, for direct semantic annotation of behavior from raw video feeds.