Selective ablation of cholinergic interneurons in the striatum results in repetitive ritualistic-like behaviors

MARTOS Y; BRAZ BY; BECCARIA JP; MURER MG; BELFORTE J

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

FALAN

Rituals form part of everyday life but can become pervasivein conditions like obsessive-compulsive disorder (OCD) andTourette syndrome. Dysfunctions in basal ganglia, includingreduced number of striatal cholinergic interneurons (SCIN),have been involved in their pathophysiology. To explorethe role of SCIN in relation to perseverative behaviors wecharacterized a new transgenic mouse model in whichinducible ablation of SCIN is achieved with high efficiencyin a cell-type and region specify manner. Here we showthat SCIN ablation results in increased repetitive behaviorswithout alteration of motor coordination, balance, orgeneral locomotion. Interestingly, only environmentallydriven,but not self-directed, repetitive behaviors areexacerbated in lesioned mice. Remarkably, SCIN ablationalso leads to exacerbated social interactions, where thenormal pattern of social exploration is continuouslyreplayed by lesioned animal. In vivo electrophysiologicalrecordings indicate that SCIN ablation results in an increaseof the functional connectivity between different corticalareas and the motor, but not associative region, of thestriatum. Our results identify a role of SCIN in suppressingperseverative behaviors including social related ones.We show that selective SCIN ablation in mice leads toexacerbated ritualistic-like behaviors that impact on socialperformance providing a link between SCIN dysfunctionand social impairments observed in OCD and Tourettepatients