
Brief intro:
- Author: Baolin Guo , Jing Chen, Qian Chen, Keke Ren, Dayun Feng, Honghui Mao, Han Yao, Jing Yang, Haiying Liu, Yingying Liu, Fan Jia, Chuchu Qi, Taylor Lynn-Jones, Hailan Hu ,Zhanyan Fu, Guoping Feng , Wenting Wang and Shengxi Wu
- Journal: Nature Neuroscience
- Doi: https://www.doi.org/10.1038/s41593-091-0445-9
- Publication Date: 2019 May 27
Products/Services used in the paper
Quotation shows PackGene:We then chose gRNA2, which had the best efficiency, to package in AAV serotype 8 (PackGene Biotech) for administration to the mice.
Research Field:CNS
AAV Serotype:AAV2/8
Targeted organ:brain
Animal or cell line strain:The Shank3B−/−, CKI (Shank3fx/fx) and Thy1-GCaMP3 mouse strains have been previously haracterized15,21,50, and all mice had a pure C57BL/6J background. Male and female mice aged 2–6 months old were used in the electrophysiological experiments. All virus injections were administered to mice aged 2–3 months old.
Abstract
Social deficit is a core clinical feature of autism spectrum disorder (ASD) but the underlying neural mechanisms remain largely unclear. We demonstrate that structural and functional impairments occur in glutamatergic synapses in the pyramidal neurons of the anterior cingulate cortex (ACC) in mice with a mutation in Shank3, a high-confidence candidate ASD gene. Conditional knockout of Shank3 in the ACC was sufficient to generate excitatory synaptic dysfunction and social interaction deficits, whereas selective enhancement of ACC activity, restoration of SHANK3 expression in the ACC, or systemic administration of an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor positive modulator improved social behavior in Shank3 mutant mice. Our findings provide direct evidence for the notion that the ACC has a role in the regulation of social behavior in mice and indicate that ACC dysfunction may be involved in social impairments in ASD.
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