Deficiency of Shank3 in the nucleus accumbens reveals a loss of social-specific motivation Article Swipe

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Oakleigh M. Folkes , Meaghan Donahue , Sung Eun Wang , Paola N. Negrón-Moreno , Nicole Xinyen Oo , Sheng-Nan Qiao , Xiaoming Wang , Yong-hui Jiang ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.1038/s42003-025-08942-8

Social behavior deficits are a hallmark of autism and other neuropsychiatric disorders. SHANK3, a common causal gene for autism, is highly expressed in the nucleus accumbens (NAc), a critical brain region for social behaviors. We previously characterized conventional Shank3^Δe4-22 deletion mice with increased unilateral social investigation and hypoactive NAc circuits. Here, we describe a new exon 4-22 floxed (Shank3^flox/flox) mouse line that we developed to test the hypothesis that SHANK3 in the NAc is necessary for social behaviors. We find that knockdown of Shank3 in the NAc of male and female mice decreases social preference in the 3-chamber assay and decreases social motivation in the social conditioned place preference assay. Shank3 NAc deficiency does not alter food reward seeking, reciprocal social investigation, or anxiety-like behaviors, which we report in conventional Shank3^Δe4-22 deletion mice. These data elucidate a specific mechanism of Shank3 in the NAc on social behavior and social motivation.

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Developmental Psychology

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Nucleus accumbens Psychology Autism Gene knockdown Neuroscience Mechanism (biology) Conditioned place preference Social behavior Developmental psychology Social identity approach Preference Biology Social relation Endophenotype Genetics Social discrimination Social inhibition Exon Mutation Social isolation Social preferences Food intake Neurogenetics

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Type: article
Language: en
Landing Page: https://doi.org/10.1038/s42003-025-08942-8
PDF: https://www.nature.com/articles/s42003-025-08942-8.pdf
OA Status: gold
References: 69
OpenAlex ID: https://openalex.org/W7105644367

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DOI: https://doi.org/10.1038/s42003-025-08942-8

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Title: Deficiency of Shank3 in the nucleus accumbens reveals a loss of social-specific motivation

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Language: en

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Publication year: 2025

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Publication date: 2025-11-14

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Authors: Oakleigh M. Folkes, Meaghan Donahue, Sung Eun Wang, Paola N. Negrón-Moreno, Nicole Xinyen Oo, Sheng-Nan Qiao, Xiaoming Wang, Yong-hui Jiang

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Landing page: https://doi.org/10.1038/s42003-025-08942-8

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Concepts: Nucleus accumbens, Psychology, Autism, Gene knockdown, Neuroscience, Mechanism (biology), Conditioned place preference, Social behavior, Developmental psychology, Social identity approach, Preference, Biology, Social relation, Endophenotype, Genetics, Social discrimination, Social inhibition, Exon, Mutation, Social isolation, Social preferences, Food intake, Neurogenetics

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