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Although long associated with dysfunction within the cortico-striato-thalamic-cortical circuits, the thalamic role in OCD pathogenesis remains highly understudied in the literature. Here, we identified a rat thalamic nucleus \u2013 the reuniens (NRe) \u2013 that mediates persistent, compulsive self-grooming behavior. Optogenetic activation of this nucleus triggers immediate, excessive grooming with strong irresistibility, increases anxiety, and induces negative affective valence. A thalamic-hypothalamic pathway linking NRe to the dorsal premammillary nucleus (PMd) was discovered to mediate excessive self-grooming behavior and render it a defensive coping response to stress, mirroring the compulsions faced by OCD patients. Given the close resemblance between this self-grooming behavior and the clinical manifestations of OCD, the results from this study highlight the role of NRe in mediating OCD-like compulsive behaviors. This can be attributed to NRe\u2019s position at the nexus of an extensive frontal-striatal-thalamic network regulating cognition, emotion, and stress-related behaviors, suggesting NRe as a potential novel target for intervention.<\/jats:p>","DOI":"10.1038\/s41398-025-03283-w","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T02:35:07Z","timestamp":1740450907000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The midline thalamic nucleus reuniens promotes compulsive-like grooming in rodents"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3927-9885","authenticated-orcid":false,"given":"Romeo Chen Wei","family":"Goh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Dao","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing-Ho","family":"Yung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8166-6653","authenticated-orcid":false,"given":"Ya","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"3283_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphar.2019.01362","volume":"10","author":"AP Escobar","year":"2019","unstructured":"Escobar AP, Wendland JR, Ch\u00e1vez AE, Moya PR. 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