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Publication : Reduced sociability and social agency encoding in adult Shank3-mutant mice are restored through gene re-expression in real time.

First Author  Lee DK Year  2021
Journal  Nat Neurosci Volume  24
Issue  9 Pages  1243-1255
PubMed ID  34253921 Mgi Jnum  J:323399
Mgi Id  MGI:7263120 Doi  10.1038/s41593-021-00888-4
Citation  Lee DK, et al. (2021) Reduced sociability and social agency encoding in adult Shank3-mutant mice are restored through gene re-expression in real time. Nat Neurosci 24(9):1243-1255
abstractText  Despite a growing understanding of the molecular and developmental basis of autism spectrum disorder (ASD), how the neuronal encoding of social information is disrupted in ASD and whether it contributes to abnormal social behavior remains unclear. Here, we disrupted and then restored expression of the ASD-associated gene Shank3 in adult male mice while tracking the encoding dynamics of neurons in the medial prefrontal cortex (mPFC) over weeks. We find that Shank3 disruption led to a reduction of neurons encoding the experience of other mice and an increase in neurons encoding the animal's own experience. This shift was associated with a loss of ability by neurons to distinguish other from self and, therefore, the inability to encode social agency. Restoration of Shank3 expression in the mPFC reversed this encoding imbalance and increased sociability over 5-8 weeks. These findings reveal a neuronal-encoding process that is necessary for social behavior and that may be disrupted in ASD.
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