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<p>AMPA receptors mediate the majority of excitatory synaptic transmission in the central nervous system, and are essential for LTP/LTD through insertion into/removal from postsynaptic density. Experimental manipulation (pharmacological, genetic) of AMPA receptors affects synaptic plasticity and has important implications for learning and memory and neurological diseases. We found that bilateral expression of the GluA1 C80 peptide in the dorsal hippocampus CA1 region acutely blocked endogenous GluA1 function, significantly affected the synaptic plasticity, which led to impairments in short-term spatial memory but not long-term spatial memory in mice. Mechanistically, our results revealed that the GluA1 C80 peptide might impair LTP and short-term spatial memory through interference of the binding between GluA1 to 4.1N. Our study suggests that the GluA1 C80 peptide could serve as a useful tool for acute manipulation of endogenous AMPA receptors in a brain region-specific manner <i>in vivo</i>.</p>

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GluA1 C80 Peptide Impairs Short-Term Spatial Memory in Mice by Interfering with the 4.1N Binding Site

  • 期刊论文

  • 发表日期：

    2025年12月19日

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  • Yongfeng Li,
  • Jinpeng Wang,
  • Xiaoya Zhang,
  • Junzhao Li,
  • Kongjie Lu,
  • Zhaodi Liu,
  • Bizheng Wang,
  • Xuewei Yang,
  • Yong Zhang

摘要

AMPA receptors mediate the majority of excitatory synaptic transmission in the central nervous system, and are essential for LTP/LTD through insertion into/removal from postsynaptic density. Experimental manipulation (pharmacological, genetic) of AMPA receptors affects synaptic plasticity and has important implications for learning and memory and neurological diseases. We found that bilateral expression of the GluA1 C80 peptide in the dorsal hippocampus CA1 region acutely blocked endogenous GluA1 function, significantly affected the synaptic plasticity, which led to impairments in short-term spatial memory but not long-term spatial memory in mice. Mechanistically, our results revealed that the GluA1 C80 peptide might impair LTP and short-term spatial memory through interference of the binding between GluA1 to 4.1N. Our study suggests that the GluA1 C80 peptide could serve as a useful tool for acute manipulation of endogenous AMPA receptors in a brain region-specific manner in vivo.