Relocation of an Extrasynaptic GABA(A) Receptor to Inhibitory Synapses Freezes Excitatory Synaptic Strength and Preserves Memory

Davenport Christopher M.; Rajappa Rajit; Katchan Ljudmila; Taylor Charlotte R.; Tsai Ming-Chi; Smith Caleb M.; de Jong Johannes W.; Arnold Don B.; Lammel Stephan; Kramer Richard H.

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Relocation of an Extrasynaptic GABA(A) Receptor to Inhibitory Synapses Freezes Excitatory Synaptic Strength and Preserves Memory

机译：抑制突出突触突触突触（A）受体的迁移冻结兴奋性突触强度并保留记忆

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The excitatory synapse between hippocampal CA3 and CA1 pyramidal neurons exhibits long-term potentiation (LTP), a positive feedback process implicated in learning and memory in which postsynaptic depolarization strengthens synapses, promoting further depolarization. Without mechanisms for interrupting positive feedback, excitatory synapses could strengthen inexorably, corrupting memory storage. Here, we reveal a hidden form of inhibitory synaptic plasticity that prevents accumulation of excitatory LTP. We developed a knockin mouse that allows optical control of endogenous alpha 5-subunit-containing gamma-aminobutyric acid (GABA)(A) receptors (alpha 5-GABARs). Induction of excitatory LTP relocates alpha 5-GABARs, which are ordinarily extrasynaptic, to inhibitory synapses, quashing further NMDA receptor activation necessary for inducing more excitatory LTP. Blockade of alpha 5-GABARs accelerates reversal learning, a behavioral test for cognitive flexibility dependent on repeated LTP. Hence, inhibitory synaptic plasticity occurs in parallel with excitatory synaptic plasticity, with the ensuing interruption of the positive feedback cycle of LTP serving as a possible critical early step in preserving memory.

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《Neuron》 |2021年第1期|共17页
作者
Davenport Christopher M.; Rajappa Rajit; Katchan Ljudmila; Taylor Charlotte R.; Tsai Ming-Chi; Smith Caleb M.; de Jong Johannes W.; Arnold Don B.; Lammel Stephan; Kramer Richard H.;
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作者单位

Univ Calif Berkeley Dept Mol &

Cell Biol 229 Stanley Hall Berkeley CA 94720 USA;

Univ Calif Berkeley Dept Mol &

Cell Biol 229 Stanley Hall Berkeley CA 94720 USA;

Univ Calif Berkeley Dept Mol &

Cell Biol 229 Stanley Hall Berkeley CA 94720 USA;

Univ Calif Berkeley Dept Mol &

Cell Biol 229 Stanley Hall Berkeley CA 94720 USA;

Univ Calif Berkeley Dept Mol &

Cell Biol 229 Stanley Hall Berkeley CA 94720 USA;

Univ Calif Berkeley Dept Mol &

Cell Biol 229 Stanley Hall Berkeley CA 94720 USA;

Univ Calif Berkeley Dept Mol &

Cell Biol 229 Stanley Hall Berkeley CA 94720 USA;

Univ Southern Calif Sect Mol &

Computat Biol Dept Biol Los Angeles CA 90089 USA;

Univ Calif Berkeley Dept Mol &

Cell Biol 229 Stanley Hall Berkeley CA 94720 USA;

Univ Calif Berkeley Dept Mol &

Cell Biol 229 Stanley Hall Berkeley CA 94720 USA;

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正文语种 eng
中图分类神经病学;
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1. Changes in synaptic and extrasynaptic N-methyl-D-aspartate receptor-mediated currents at early-stage epileptogenesis in adult mice [J] . Juegang Ju, Sheng-tian Li 中国神经再生研究：英文版 . 2011,第002期
2. GABA(B) receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneurons. [J] . Lei S, McBain CJ The Journal of Physiology . 2003,第Pta2期

机译：GABA（B）受体对大鼠CA3海马中间神经元的兴奋性和抑制性突触传递的调节。
3. GHB depresses fast excitatory and inhibitory synaptic transmission via GABA(B) receptors in mouse neocortical neurons. [J] . Jensen K, Mody I Cerebral cortex . 2001,第5期

机译：GHB通过小鼠新皮层神经元中的GABA（B）受体抑制快速的兴奋性和抑制性突触传递。
4. Comparison of antagonist potencies at pre-and post-synaptic GABA_B receptors at inhibitory synapses in the CA1 region of the Rat hippocampus [J] . M. F. Pozza, N. A. Manuel, M. Steinmann British Journal of Pharmacology . 1999,第1期

机译：大鼠海马CA1区突触前和突触后GABA_B受体抑制性突触的拮抗剂效能比较
5. The Effect of Different Types of Synaptic Plasticity on the Performance of Associative Memory Networks with Excitatory and Inhibitory Sub-populations [C] . Alex Metaxas, Reinoud Maex, Volker Steuber, Information processing in cells and tissues. . 2012

机译：不同类型的突触可塑性对具有兴奋性和抑制性亚群的联想记忆网络性能的影响
6. All for One But Not One for All: Excitatory Synaptic Scaling and Intrinsic Excitability are Coregulated by Camkiv, While Inhibitory Synaptic Scaling is Under Independent Control [D] . Joseph, Annelise K. 2017

机译：一劳永逸：Camkiv调节了兴奋性突触缩放和内在兴奋性，而抑制性突触缩放则在独立控制下
7. γ1-Containing GABA-A Receptors Cluster at Synapses Where they Mediate Slower Synaptic Currents than γ2-Containing GABA-A Receptors [O] . Christine L. Dixon, Pankaj Sah, Angelo Keramidas, 2017

机译：包含γ1的GABA-A受体聚集在突触处它们比包含γ2的GABA-A受体介导更慢的突触电流。
8. Activation of presynaptic GABA(B(1a,2)) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses [O] . Wedemeyer C., Zorrilla de San Martin J., Ballestero J., 2013

机译：突触前GaBa（B（1a，2））受体的激活抑制哺乳动物抑制性胆碱能橄榄耳 - 毛细胞突触的突触传递。

Relocation of an Extrasynaptic GABA(A) Receptor to Inhibitory Synapses Freezes Excitatory Synaptic Strength and Preserves Memory

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