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Enriched Environment Enhances Sociability Through the Promotion of ESyt1-Related Synaptic Formation in the Medial Prefrontal Cortex

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Abstract

Sociability stands as a crucial factor in the evolutionary success of all mammalian species. Notably, enriched environment (EE) housing has been shown to enhance sociability in mice. However, the precise underlying molecular mechanism remains elusive. In this study, we established an EE paradigm, housing mice for a 14-day period. Both enhanced sociability and an increased spine density in the medial prefrontal cortex (mPFC) of mice subjected to EE were detected. To elucidate the potential molecular pathway, we conducted high-performance liquid chromatography tandem mass spectrometry (HPLC–MS) analysis of the entire mPFC from both EE and home-caged (HC) housed mice. Our analysis identified 16 upregulated and 20 downregulated proteins in the EE group. Among them, Extended Synaptotagmin 1 (ESyt1), an activity-dependent endoplasmic reticulum (ER)–plasma membrane (PM) tethering protein associated with synaptic function and growth, emerged as a potentially key player in the increased synapse formation and enhanced sociability observed in EE-housed mice. Further investigation, involving the knockdown of ESyt1 expression via sh ESyt1 lentivirus in the mPFC, revealed that ESyt1 is crucial for increased spine density of mPFC and enhanced sociability of mice in an enriched environment but not in normal condition. Overall, our findings uncover a novel mechanistic insight into the positive influence of environmental enrichment on social behavior via ESyt1-mediated pathways.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from the Science and Technology Program of the Health Commission of Fujian Province, the Fujian Major Research Grants for Young and Middle-aged Health Professionals (Grant Number: 2021ZQNZD007) awarded to Zheng Yu, and the Science and Technology Program of the Health Commission of Fujian Province (Grant Number: 2022GGB005) awarded to Meili Yang.

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Authors and Affiliations

  1. Translational Medicine Immunology Laboratory, Clinical Research Center, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian Province, China

    Meiying Zhang, Shitu Zhuo & Zheng Yu

  2. Queen Mary School of Nanchang University, Nanchang, 330031, Jiangxi Province, China

    Xianghe Li

  3. Department of Neurology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian Province, China

    Shitu Zhuo, Meili Yang & Zheng Yu

Authors
  1. Meiying Zhang
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  2. Xianghe Li
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  3. Shitu Zhuo
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  4. Meili Yang
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  5. Zheng Yu
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Contributions

MZ, XL, and SZ performed the experiments. ZY conceived and designed the research. ZY and MZ contributed to the creation of the table and figures. XL and ML conducted the statistical analysis. ZY wrote the paper. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Meili Yang or Zheng Yu.

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The animal protocols in this study were approved by the Fujian Medical University Medical Sciences Committee (China) for research in vertebrate animal.

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The authors declare no competing interests.

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Meiying Zhang and Xianghe Li contributed equally to this work as co-first authors.

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Zhang, M., Li, X., Zhuo, S. et al. Enriched Environment Enhances Sociability Through the Promotion of ESyt1-Related Synaptic Formation in the Medial Prefrontal Cortex. Mol Neurobiol 61, 3019–3030 (2024). https://doi.org/10.1007/s12035-023-03742-9

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  • DOI: https://doi.org/10.1007/s12035-023-03742-9

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