222 | Inhibition of striatal cholinergic interneurons by chemogenetic manipulation induce compulsive and perseverative behaviors in mice.

Neural Circuits and Systems Neuroscience

Author: Andrés Pablo Varani | Email: andresvarani@gmail.com

Andrés P Varani , Martina Gomez Acosta , Cecilia Tubert , Gustavo Almeida Aguiar , Carlos A Pretell Annan , Juan E Belforte

1° Instituto de Fisiología y Biofísica Bernardo Houssay (Instituto Universidad de Buenos Aires – Consejo Nacional de Investigaciones Científicas y Técnicas). Paraguay 2155, 7°piso, (CP: 1121), Ciudad de Buenos Aires, Argentina.

A reduced number of striatal cholinergic interneurons (SCIN) could be implicated in neuropsychiatric conditions like obsessive-compulsive disorder and Tourette syndrome. Previous research showed altered social interactions and increased repetitive behaviors after selective SCIN ablation. However, whether these alterations are related to SCIN signaling impairment or to plastic changes emerging after SCIN lesion, remain uncertain. To explore acute SCIN inhibition effects, ChatCre heterozygous mice were injected with a viral vector (pAAV-hSyn-DIO-hM4DGi-mCherry) to selectively express an inhibitory DREADD in SCIN. Comprehensive behavioral tests, including open field, hole board, marble burying, nesting, grooming, and social interaction assessment, were conducted using CNO or vehicle. Although locomotion in CNO treated mice remained normal, SCIN inhibition notably increased head dippings during the hole board test. Furthermore, SCIN inhibition led to more buried marbles, frayed cotton for nest assembly, and grooming events, but had no effect on social interactions. Immunofluorescence (anti-mCherry and anti-Chat) confirmed DREADD expression specificity in SCIN. Ex-vivo validation demonstrated significant reduction in SCIN spontaneous firing frequency upon CNO application. In summary, acute SCIN inhibition exacerbated ritualistic behaviors in mice, supporting the notion that SCIN may play a role in suppressing compulsive and perseverative behaviors seen in psychiatric disorders.