Hyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior

• DOI: 10.1038/s41467-024-48331-z
• Publication Date: 2024-05-24T16:02:04Z
• Authors: Sean C. Piantadosi; Elizabeth E. Manning; Brittany L. Chamb...; James Hyde; Zoe LaPalombara; Nicholas M. Bannon; Jamie L. Pierson; Vijay M. K Namboo...; Susanne E. Ahmari
• Keywords: Medium spiny neuron

Abstract Compulsive behaviors are a hallmark symptom of obsessive compulsive disorder (OCD). Striatal hyperactivity has been linked to behavior generation in correlative studies humans and causal rodents. However, the contribution two distinct striatal output populations treatment is unknown. These direct indirect pathway-projecting spiny projection neurons (SPNs) have classically thought promote or suppress actions, respectively, leading long-held hypothesis that increased relative pathway promotes behavior. Contrary this hypothesis, here we find associated with grooming Sapap3 -knockout mouse model OCD-relevant Furthermore, show suppression activity using optogenetics first-line OCD pharmacotherapy fluoxetine reduced -knockouts. Together, these findings highlight as potential target for