Pathway-specific alterations in striatal excitability and cholinergic modulation in a SAPAP3 mouse model of compulsive motor behavior.

ABSTRACT: Deletion of the obsessive-compulsive disorder (OCD)-associated gene SAP90/PSD-95-associated protein 3 (Sapap3), which encodes a postsynaptic anchoring protein at corticostriatal synapses, causes OCD-like motor behaviors in mice. While corticostriatal synaptic dysfunction is central to this phenotype, the striatum efficiently adapts to pathological changes, often in ways that expand upon the original circuit impairment. Here, we show that SAPAP3 deletion causes non-synaptic and pathway-specific alterations in dorsolateral striatum circuit function. While somatic excitability was elevated in striatal projection neurons (SPNs), dendritic excitability was exclusively enhanced in direct pathway SPNs. Layered on top of this, cholinergic modulation was altered in opposing ways: striatal cholinerg

SUBMITTER: Malgady JM 

PROVIDER: S-EPMC10872927 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature