Year: 2025
Type: article
Abstract: ABSTRACT Deficits in social interaction are a hallmark symptom of autism and other neuropsychiatric disorders. SHANK3 encodes a postsynaptic density scaffold protein and is one of the most common causal genes for autism. SHANK3 protein is highly expressed in the nucleus accumbens (NAc), a critical brain region underlying motivated behavior, including social motivation. We previously reported that global Shank3 Δe 4–22 deletion mice have decreased motivation for palatable food, increased unilateral social investigation, and show a hypoactive NAc and NAc-connected circuits. We thus developed a new Shank3 flox/flox mouse tool to conditionally knockdown SHANK3 in a region-specific manner. We found that knockdown of Shank3 in the NAc decreased social preference in the 3-chamber assay and decreased social motivation in the social conditioned place preference (sCPP) assay. Shank3- NAc deletion did not alter food reward seeking, reciprocal social investigation, or anxiety-like behaviors, that we report in global Shank3 Δe 4–22 deletion mice. These data establish a novel and specific role of Shank3 in the NAc on social motivation.
Source: Communications Biology
Institutions: Yale University, Duke University, Duke Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Awards: G1591514141, G2148533500, G219547240, G2511928839, G3126391803, G366210743, G4298931846, Investigations of Neuronal Ensembles and Shank3-Homer Scaffolds on Reward and Social Behavior in a Shank3 model of Autism, A novel neural circuit analysis paradigm to model autism in mice, A novel paradigm to dissect the function connectivity in Shank3 autism model, G5877060227, G6880294049, Molecular and circuitry mechanism underlying autism behaviors in Shank3 mouse models, G7751497159, G7836263131, Analysis of Shank3 Complete and Temporal and Spatial Specific Knockout Mice, G8846410786, G9000310465
OpenAlex ID: W4416225772