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ChIs comprise only 1 to 2% of striatal neurons but project widely throughout the stratum to impact various striatal neurotransmission, including TS\u2010related dopaminergic transmission. Here, we link striatal Slitrk1, ChI function, and dopaminergic transmission and their associations with TS\u2010like tic behaviors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Slitrk1<\/jats:italic>\u2010KD mice were induced by bilaterally injecting <jats:italic>Slitrk1<\/jats:italic> siRNA into their dorsal striatum. Control mice received scrambled siRNA injection. Their TS\u2010like tic behaviors, prepulse inhibition, sensory\u2010motor function and dopamine\u2010related behaviors were compared. We also compared dopamine and ACh levels in microdialysates, Slitrk protein and dopamine transporter levels, and numbers of Slitrk\u2010positive ChIs and activated ChIs in the striatum between two mouse groups, and electrophysiological properties between Slitrk\u2010positive and Slitrk\u2010negative striatal ChIs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Slitrk1<\/jats:italic>\u2010KD mice exhibit TS\u2010like haloperidol\u2010sensitive stereotypic tic behaviors, impaired prepulse inhibition, and delayed sensorimotor response compared with the control group. These TS\u2010like characteristics correlate with lower striatal Slitrk1 protein levels, fewer Slitrk1\u2010containing ChIs, and fewer activated ChIs in <jats:italic>Slitrk1<\/jats:italic>\u2010KD mice. Based on their electrophysiological properties, Slitrk1\u2010negative ChIs are less excitable than Slitrk1\u2010positive ChIs. <jats:italic>Slitrk1<\/jats:italic>\u2010KD mice have lower evoked acetylcholine and dopamine levels, higher tonic dopamine levels, and downregulated dopamine transporters in the striatum, increased apomorphine\u2010induced climbing behaviors, and impaired methamphetamine\u2010induced hyperlocomotion compared with controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Slitrk1 is pivotal in maintaining striatal ChIs activity and subsequent dopaminergic transmission for normal motor functioning. Furthermore, conditional striatal Slitrk1\u2010KD mice may serve as a translational modality with aspects of TS phenomenology. 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