Growing evidence indicates that GABAergic interneurons play a pivotal role to generate brain oscillation patterns, which are fundamental for the mnemonic processing of the hippocampus. While acetylcholine (ACh) is a powerful modulator of synaptic plasticity and brain function, few studies have been focused on the role of cholinergic signaling in the regulation of GABAergic inhibitory synaptic plasticity. We have previously shown that co-activation of endocannabinoids (CB1R) and muscarinic receptor (mAChR) in hippocampal interneurons can induce activity-dependent GABAergic long-term depression in CA1 pyramidal neurons. Here, using electrophysiological and pharmacological approaches in acute rat hippocampal slices, we show that activation of cholinergic receptors followed by either high-frequency stimulation of Schaeffer collaterals or exogenous activation of metabotropic glutamate receptor (mGluR) induces a robust long-term potentiation at GABAergic synapses (iLTP). These forms of iLTP are blocked by the M1 type of mAChR (MR1) or by the group I of mGluR (mGluR1/5) antagonists. These results suggest the existence of spatiotemporal cooperativity between cholinergic and glutamatergic pathways where activation of mAChR serves as a metaplastic switch making glutamatergic synapses capable to induce long-term potentiation at inhibitory synapses, that may contribute to the modulation of brain mechanisms of learning and memory.

中文翻译：

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毒蕈碱受体对 GABA 能长期增强作用的启动。

越来越多的证据表明，GABAergic 中间神经元在产生大脑振荡模式方面发挥着关键作用，这对于海马体的记忆处理至关重要。虽然乙酰胆碱 (ACh) 是突触可塑性和脑功能的强大调节剂，但很少有研究关注胆碱能信号在调节 GABA 能抑制性突触可塑性中的作用。我们之前已经表明，海马中间神经元中内源性大麻素 (CB1R) 和毒蕈碱受体 (mAChR) 的共同激活可以在 CA1 锥体神经元中诱导活性依赖性 GABA 能长期抑制。在这里，在急性大鼠海马切片中使用电生理学和药理学方法，我们表明，胆碱能受体的激活，然后是 Schaeffer 侧枝的高频刺激或代谢型谷氨酸受体 (mGluR) 的外源性激活，会在 GABA 能突触 (iLTP) 处引起强烈的长期增强。这些形式的 iLTP 被 M1 型 mAChR (MR1) 或第 I 组 mGluR (mGluR1/5) 拮抗剂阻断。这些结果表明胆碱能和谷氨酸能通路之间存在时空协同作用，其中 mAChR 的激活充当化生开关，使谷氨酸能突触能够在抑制性突触处诱导长期增强，这可能有助于调节学习和记忆的大脑机制。这些形式的 iLTP 被 M1 型 mAChR (MR1) 或第 I 组 mGluR (mGluR1/5) 拮抗剂阻断。这些结果表明胆碱能和谷氨酸能通路之间存在时空协同作用，其中 mAChR 的激活充当化生开关，使谷氨酸能突触能够在抑制性突触处诱导长期增强，这可能有助于调节学习和记忆的大脑机制。这些形式的 iLTP 被 M1 型 mAChR (MR1) 或第 I 组 mGluR (mGluR1/5) 拮抗剂阻断。这些结果表明胆碱能和谷氨酸能通路之间存在时空协同作用，其中 mAChR 的激活充当化生开关，使谷氨酸能突触能够在抑制性突触处诱导长期增强，这可能有助于调节学习和记忆的大脑机制。