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Repetitive stereotyped behavior (e.g., grooming), a featured symptom in OCD, has been proposed to be associated with perturbed dopamine (DA) signaling. However, the precise brain circuits participating in DA\u2019s control over this behavioral phenotype remain elusive. Here, we identified that DA neurons in substantia nigra pars compacta (SNc) orchestrate ventromedial striatum (VMS) microcircuits as well as lateral orbitofrontal cortex (lOFC) during self-grooming behavior. SNc\u2013VMS and SNc\u2013lOFC dopaminergic projections modulate grooming behaviors and striatal microcircuit function differentially. Specifically, the activity of the SNc\u2013VMS pathway promotes grooming via D1 receptors, whereas the activity of the SNc\u2013lOFC pathway suppresses grooming via D2 receptors. SNc DA neuron activity thus controls the OCD-like behaviors via both striatal and cortical projections as dual gating. These results support both pharmacological and brain-stimulation treatments for OCD.<\/jats:p>","DOI":"10.1073\/pnas.2207545119","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T15:17:01Z","timestamp":1667834221000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Midbrain dopamine neurons arbiter OCD-like behavior"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-3584","authenticated-orcid":false,"given":"Jinwen","family":"Xue","sequence":"first","affiliation":[{"name":"Minister of Education (MOE) Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210096, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Qian","sequence":"additional","affiliation":[{"name":"Minister of Education (MOE) Key Laboratory of Developmental Genes and 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