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Conditional knockout of Shank3 in the ventral CA1 by quantitative in vivo genome-editing impairs social memory in mice

Author

Listed:
  • Myung Chung

    (The University of Tokyo
    The University of Tokyo)

  • Katsutoshi Imanaka

    (The University of Tokyo
    The University of Tokyo)

  • Ziyan Huang

    (The University of Tokyo
    The University of Tokyo)

  • Akiyuki Watarai

    (The University of Tokyo)

  • Mu-Yun Wang

    (The University of Tokyo)

  • Kentaro Tao

    (The University of Tokyo)

  • Hirotaka Ejima

    (The University of Tokyo)

  • Tomomi Aida

    (Massachusetts Institute of Technology)

  • Guoping Feng

    (Massachusetts Institute of Technology
    Broad Institute of MIT and Harvard)

  • Teruhiro Okuyama

    (The University of Tokyo
    The University of Tokyo)

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.

Suggested Citation

  • Myung Chung & Katsutoshi Imanaka & Ziyan Huang & Akiyuki Watarai & Mu-Yun Wang & Kentaro Tao & Hirotaka Ejima & Tomomi Aida & Guoping Feng & Teruhiro Okuyama, 2024. "Conditional knockout of Shank3 in the ventral CA1 by quantitative in vivo genome-editing impairs social memory in mice," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48430-x
    DOI: 10.1038/s41467-024-48430-x
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    1. Yuan Mei & Patricia Monteiro & Yang Zhou & Jin-Ah Kim & Xian Gao & Zhanyan Fu & Guoping Feng, 2016. "Adult restoration of Shank3 expression rescues selective autistic-like phenotypes," Nature, Nature, vol. 530(7591), pages 481-484, February.
    2. Philippe E. Mangeot & Valérie Risson & Floriane Fusil & Aline Marnef & Emilie Laurent & Juliana Blin & Virginie Mournetas & Emmanuelle Massouridès & Thibault J. M. Sohier & Antoine Corbin & Fabien Aub, 2019. "Genome editing in primary cells and in vivo using viral-derived Nanoblades loaded with Cas9-sgRNA ribonucleoproteins," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    3. Xiaoming Wang & Alexandra L. Bey & Brittany M. Katz & Alexandra Badea & Namsoo Kim & Lisa K. David & Lara J. Duffney & Sunil Kumar & Stephen D. Mague & Samuel W. Hulbert & Nisha Dutta & Volodya Hayrap, 2016. "Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism," Nature Communications, Nature, vol. 7(1), pages 1-18, September.
    4. Claire S Leblond & Caroline Nava & Anne Polge & Julie Gauthier & Guillaume Huguet & Serge Lumbroso & Fabienne Giuliano & Coline Stordeur & Christel Depienne & Kevin Mouzat & Dalila Pinto & Jennifer Ho, 2014. "Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments," PLOS Genetics, Public Library of Science, vol. 10(9), pages 1-15, September.
    5. Torcato Meira & Felix Leroy & Eric W. Buss & Azahara Oliva & Jung Park & Steven A. Siegelbaum, 2018. "A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    6. Tara Raam & Kathleen M. McAvoy & Antoine Besnard & Alexa H. Veenema & Amar Sahay, 2017. "Hippocampal oxytocin receptors are necessary for discrimination of social stimuli," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    7. Shiaoching Gong & Chen Zheng & Martin L. Doughty & Kasia Losos & Nicholas Didkovsky & Uta B. Schambra & Norma J. Nowak & Alexandra Joyner & Gabrielle Leblanc & Mary E. Hatten & Nathaniel Heintz, 2003. "A gene expression atlas of the central nervous system based on bacterial artificial chromosomes," Nature, Nature, vol. 425(6961), pages 917-925, October.
    8. Dheeraj S. Roy & Autumn Arons & Teryn I. Mitchell & Michele Pignatelli & Tomás J. Ryan & Susumu Tonegawa, 2016. "Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease," Nature, Nature, vol. 531(7595), pages 508-512, March.
    9. F. Ann Ran & Le Cong & Winston X. Yan & David A. Scott & Jonathan S. Gootenberg & Andrea J. Kriz & Bernd Zetsche & Ophir Shalem & Xuebing Wu & Kira S. Makarova & Eugene V. Koonin & Phillip A. Sharp & , 2015. "In vivo genome editing using Staphylococcus aureus Cas9," Nature, Nature, vol. 520(7546), pages 186-191, April.
    10. Frederick L. Hitti & Steven A. Siegelbaum, 2014. "The hippocampal CA2 region is essential for social memory," Nature, Nature, vol. 508(7494), pages 88-92, April.
    11. Jie Xu & Christopher L. Bartolome & Cho Shing Low & Xinchi Yi & Cheng-Hao Chien & Peng Wang & Dong Kong, 2018. "Genetic identification of leptin neural circuits in energy and glucose homeostases," Nature, Nature, vol. 556(7702), pages 505-509, April.
    12. Xiaoting Wu & Wade Morishita & Kevin T. Beier & Boris D. Heifets & Robert C. Malenka, 2021. "5-HT modulation of a medial septal circuit tunes social memory stability," Nature, Nature, vol. 599(7883), pages 96-101, November.
    13. Azahara Oliva & Antonio Fernández-Ruiz & Felix Leroy & Steven A. Siegelbaum, 2020. "Hippocampal CA2 sharp-wave ripples reactivate and promote social memory," Nature, Nature, vol. 587(7833), pages 264-269, November.
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