Synaptic editing of frontostriatal circuitry prevents excessive grooming in SAPAP3-deficient mice.

ABSTRACT: Synaptic dysfunction has been implicated as a key mechanism underlying the pathophysiology of psychiatric disorders. Most pharmacological therapeutics for schizophrenia, autism spectrum disorder, obsessive-compulsive disorder, and major depressive disorder temporarily augment chemical synapse function. Nevertheless, medication non-compliance is a major clinical challenge, and behavioral dysfunction often returns following pharmacotherapeutic discontinuation. Here, we deployed a designer electrical synapse to edit a single class of chemical synapses in a genetic mouse model of obsessive-compulsive disorder (OCD). Editing these synapses in juvenile mice normalized circuit function and prevented the emergence of pathological repetitive behavior in adulthood. Thus, we establish precision circu

SUBMITTER: Walder-Christensen KK 

PROVIDER: S-EPMC11974874 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature