Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons

MARTOS Y. ; BRAZ B.; BECCARIA JP. ; MURER MG: ; MURER GM; BELFORTE JE

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Lugar: Washington; Año: 2017 vol. 37 p. 2849 - 2858

0270-6474

The mechanismsunderlying social dysfunction in neuropsychiatric conditions like obsessive-compulsivedisorder (OCD) and Tourette syndrome (TS) remain uncertain. Dysfunctions inbasal ganglia, including reduced number of striatal cholinergic interneurons(SCIN), have been involved in their pathophysiology. To explore the role ofSCIN in relation to perseverative behaviors we characterized a new transgenicmouse model in which inducible ablation of SCIN is achieved with highefficiency in a cell-type and region specific manner. Mice were subjected to anextensive behavioral testing including assessment of social behaviors andcorticostriatal functional connectivity was evaluated in vivo. Selective SCINablation leads to altered social interactions together with exacerbated spontaneouslyemitted repetitive behaviors. Lesioned mice showed normal motor coordination,balance, and general locomotion. Interestingly, only environmentally-driven,but not self-directed, repetitive behaviors are exacerbated in lesioned mice.Remarkably, in mice with SCIN ablation the normal pattern of social explorationis continuously replayed. The emerging pattern of social interactions is highlypredictable and invariant across time. In vivo electrophysiological recordings indicate that SCIN ablation results in an increase ofthe functional connectivity between different cortical areas and the motor, butnot associative, region of the striatum.  Our results identify a role ofSCIN in suppressing perseverative behaviors including social related ones. Insum, SCIN ablation in mice leads to exacerbated ritualistic-like behaviors thatimpact on social performance providing a link between SCIN dysfunction andsocial impairments present in psychiatric disorders.