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Updated: Jul 11, 2025
In Vivo Wireless Optogenetic Control of Skilled Motor Behavior
Published on: November 22, 2021
Pathway-specific alterations in striatal excitability and cholinergic modulation in a SAPAP3 mouse model of
Jeffrey M Malgady1, Alexander Baez2, Zachary B Hobel1
1Department of Neurobiology & Behavior, Stony Brook University Renaissance School of Medicine, Stony Brook, NY 11794, USA; Graduate Program in Neuroscience, College of Arts & Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
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 cholinergic interneuron density and evoked acetylcholine release were elevated, while basal muscarinic modulation of SPNs was reduced. These data describe how SAPAP3 deletion alters the striatal landscape upon which impaired corticostriatal inputs will act, offering a basis for how pathological synaptic integration and unbalanced striatal output underlying OCD-like behaviors may be shaped.
