The midline thalamic nucleus reuniens promotes compulsive-like grooming in rodents.

Obsessive-compulsive disorder (OCD), a disabling and notoriously treatment-resistant neuropsychiatric disorder, affects 2-3% of the general population and is characterized by recurring, intrusive thoughts (obsessions) and repetitive, ritualistic behaviors (compulsions). 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 - the reuniens (NRe) - 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's 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.