論文 - 詳細
| RRC ID | 81987 |
|---|---|
| 著者 | Chung M, Imanaka K, Huang Z, Watarai A, Wang MY, Tao K, Ejima H, Aida T, Feng G, Okuyama T. |
| タイトル | Conditional knockout of Shank3 in the ventral CA1 by quantitative in vivo genome-editing impairs social memory in mice. |
| ジャーナル | Nat Commun |
| 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-associated Shank3 knockout 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-specific Shank3 conditional knockout (cKO) by the adeno-associated virus (AAV)- or specialized extracellular vesicle (EV)- mediated in vivo gene editing was sufficient to recapitulate the social memory impairment in male mice. Furthermore, the utilization of EV-mediated Shank3-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 of Shank3-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. |
| 巻・号 | 15(1) |
| ページ | 4531 |
| 公開日 | 2024-6-12 |
| DOI | 10.1038/s41467-024-48430-x |
| PII | 10.1038/s41467-024-48430-x |
| PMID | 38866749 |
| PMC | PMC11169449 |
| MeSH | Animals Autism Spectrum Disorder* / genetics Autism Spectrum Disorder* / metabolism CA1 Region, Hippocampal* / metabolism Dependovirus / genetics Gene Editing* Male Memory* / physiology Memory Disorders / genetics Memory Disorders / metabolism Memory Disorders / physiopathology Mice Mice, Inbred C57BL Mice, Knockout* Microfilament Proteins / genetics Microfilament Proteins / metabolism Nerve Tissue Proteins* / genetics Nerve Tissue Proteins* / metabolism Neurons / metabolism Social Behavior* |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 35 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | NIH-3T3 |