Scholarlink

<p>GABA<sub>A</sub> receptors (GABA<sub>A</sub>Rs) mediate most synaptic inhibition in the brain, but their cell-autonomous role in regulating glutamatergic transmission remains poorly understood. By targeting GABA<sub>A</sub>R β1–3 subunit alleles (<i>GABRB1-3</i>) at once, we genetically eliminated GABA<sub>A</sub>Rs in individual hippocampal CA1 pyramidal neurons. We find that single-cell silencing of GABAergic transmission does not alter AMPAR-mediated synaptic transmission, but leads to a reduction in NMDAR-mediated synaptic transmission, loss of long-term potentiation (LTP), and impaired spatial memory. Genetic rescue experiments reveal that NMDAR-mediated whole-cell currents and synaptic transmission depend on specific GABA<sub>A</sub>R subtypes and are tightly regulated by neuronal excitability. Pharmacologically restoring NMDAR function in β123-CRISPR mice rescues both LTP and spatial memory deficits induced by the loss of GABA<sub>A</sub>Rs in CA1 neurons. Our data uncover a previously unknown regulation of synaptic NMDAR functions by GABA<sub>A</sub>Rs at the single-cell level and provide insight into excitation and inhibition balance between GABA<sub>A</sub>Rs and NMDARs in the brain.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Cell-autonomous GABAARs are essential for NMDAR-mediated synaptic transmission, LTP, and spatial memory

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月30日

查看全文
  • Jing-jing Duan,
  • Bin Jiang,
  • Wei Yin,
  • Yuan Lin,
  • Guang-mei Yan,
  • Wei Lu

摘要

GABAA receptors (GABAARs) mediate most synaptic inhibition in the brain, but their cell-autonomous role in regulating glutamatergic transmission remains poorly understood. By targeting GABAAR β1–3 subunit alleles (GABRB1-3) at once, we genetically eliminated GABAARs in individual hippocampal CA1 pyramidal neurons. We find that single-cell silencing of GABAergic transmission does not alter AMPAR-mediated synaptic transmission, but leads to a reduction in NMDAR-mediated synaptic transmission, loss of long-term potentiation (LTP), and impaired spatial memory. Genetic rescue experiments reveal that NMDAR-mediated whole-cell currents and synaptic transmission depend on specific GABAAR subtypes and are tightly regulated by neuronal excitability. Pharmacologically restoring NMDAR function in β123-CRISPR mice rescues both LTP and spatial memory deficits induced by the loss of GABAARs in CA1 neurons. Our data uncover a previously unknown regulation of synaptic NMDAR functions by GABAARs at the single-cell level and provide insight into excitation and inhibition balance between GABAARs and NMDARs in the brain.