Muscarinic Long-Term Enhancement of Tonic and Phasic GABA(A) Inhibition in Rat CA1 Pyramidal Neurons.

Muscarinic Long-Term Enhancement of Tonic and Phasic GABA(A) Inhibition in Rat CA1 Pyramidal Neurons.
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DOI:
10.3389/fncel.2016.00244
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发表时间:
2016
影响因子:
5.3
通讯作者:
Buño W
Buño W
中科院分区:
医学2区
文献类型:
--
作者:
Domínguez S;Fernández de Sevilla D;Buño W

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乙酰胆碱(ACh)通过控制大鼠CA 1锥体神经元(PC)的兴奋和抑制来调节海马网络的运作,后者通过γ-氨基丁酸A型受体(GABAARs)。虽然已经报道了ACh对GABAARs的增强作用,但其在调节紧张性GABAA抑制中的作用尚未深入探讨。因此,我们的目的是确定ACh受体的激活对突触和突触外GABAARs介导的反应的影响。在这里,我们表明,离子型谷氨酸受体ACh的封锁下,通过毒蕈碱1型受体的作用,与突触后去极化配对诱导的强直性GABAA电流(tGABAA)和吹气诱发的GABAA电流(pGABAA)的长期增强。ACh与去极化组合也增强IPSC(即,阶段性抑制),没有与pGABAA和tGABAA的突触反应相互作用的迹象,表明两种不同的GABAA受体池的贡献。GABAA电流和IPSC的长期增强降低了PC的兴奋性,可能调节行为动物的可塑性和学习。
Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported, its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals.
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