McGill University, Département de Psychiatrie
Douglas Institut universitaire en santé mentale
Cholinergic interneurons (Chis) are pivotal regulators of striatal functions. They have the particularity to express both the vesicular acetylcholine transporter (VAChT) and the atypical type 3 vesicular glutamate transporter (VGLUT3). Consequently, they regulate the striatal network with both acetylcholine (ACh) and glutamate. We previously identified the missense polymorphism VGLUT3-p.T8I (threonine at position 8 changed to an isoleucine) in patients with substance use disorders (SUD) or eating disorders (ED). Using a rodent model (VGLUT3T8I/T8I mice), we found that the variant was causative in SUD and ED and identified an underlying mechanism. This led to a treatment that alleviate ED in mutant mice and potentially in humans.