論文

2024年1月23日

Conditional knockout ofShank3in the ventral CA1 by quantitativein vivogenome-editing impairs social memory

  • Myung Chung
  • ,
  • Katsutoshi Imanaka
  • ,
  • Ziyan Huang
  • ,
  • Akiyuki Watarai
  • ,
  • Mu-Yun Wang
  • ,
  • Kentaro Tao
  • ,
  • Hirotaka Ejima
  • ,
  • Tomomi Aida
  • ,
  • Guoping Feng
  • ,
  • Teruhiro Okuyama

DOI
10.1101/2024.01.22.576000
出版者・発行元
Cold Spring Harbor Laboratory

Abstract

Individuals with autism spectrum disorder (ASD) have a higher prevalence of social memory impairment. A series of our previous studies revealed that hippocampal ventral CA1 (vCA1) neurons possess social memory engram and that the neurophysiological representation of social memory in the vCA1 neurons is disrupted in ASD-associatedShank3knockout mice. However, whether the dysfunction of Shank3 in vCA1 causes the social memory impairment observed in ASD remains unclear. In this study, we found that vCA1-specificShank3conditional knockout (cKO) by the adeno-associated virus (AAV)- or specialized extracellular vesicle (EV)-mediatedin vivogene editing was sufficient to recapitulate the social memory impairment in male mice. Furthermore, the utilization of EV-mediatedShank3-cKO allowed us to quantitatively examine the role of Shank3 in social memory. Our results suggested that there is a certain threshold for the proportion ofShank3-cKO neurons required for social memory disruption. Thus, our study provides insight into the population coding of social memory in vCA1, as well as the pathological mechanisms underlying social memory impairment in ASD.

リンク情報
DOI
https://doi.org/10.1101/2024.01.22.576000
URL
https://syndication.highwire.org/content/doi/10.1101/2024.01.22.576000
ID情報
  • DOI : 10.1101/2024.01.22.576000

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