STIMULATION OF α1-ADRENOCEPTORS FACILITATES GABAergic TRANSMISSION ONTO PYRAMIDAL NEURONS IN THE MEDIAL PREFRONTAL CORTEX
STIMULATION OF α1-ADRENOCEPTORS FACILITATES GABAergic TRANSMISSION ONTO PYRAMIDAL NEURONS IN THE MEDIAL PREFRONTAL CORTEX
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DOI：
10.1016/j.neuroscience.2015.04.070
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发表时间：
2015-08-06
期刊：
影响因子：
3.3
通讯作者：
Cheng, Z. -Y.
中科院分区：
文献类型：
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作者：
Luo, F.;Tang, H.;Cheng, Z. -Y.
虽然α(1)-肾上腺素受体（α (1)-ARs）的激活可调节谷氨酸能的传递，但α (1)-ARs在内侧前额叶皮层（mPFC） gaba能传递中的作用尚不清楚。在这里，我们研究了α (1)-AR激动剂苯肾上腺素（Phe）对gaba能传递到mPFC深层锥体神经元的影响。我们发现Phe的剂量依赖性地增加了诱导的IPSCs （eIPSCs）的振幅。Phe增加了微型IPSCs （mIPSCs）的频率，但没有增加其振幅。Ca2+内流通过t型电压门控钙通道是ph诱导的GABA释放增加所必需的。苯丙氨酸增加了GABA的释放概率和可释放囊泡的数量。苯丙氨酸能使快速尖峰（FS）中间神经元去极化，但不影响中间神经元动作电位（APs）的放电速率。ph诱导的去极化与细胞外Na+、Ca2+和t型钙通道无关，但需要向内整流K+通道（Kirs）。本研究表明，苯丙氨酸通过抑制中间神经元Kirs增强gaba能向mPFC锥体神经元的传递，这进一步使中间神经元去极化，导致通过t型钙通道的Ca2+内流增加。我们的研究结果可能提供一种细胞和分子机制，有助于解释α (1)- ar诱导的PFC功能障碍。(c) 2015年。Elsevier Ltd.出版。版权所有。
Whereas activation of alpha(1)-adrenoceptors (alpha(1)-ARs) modulates glutamatergic transmission, the roles of alpha(1)-ARs in GABAergic transmission in the medial prefrontal cortex (mPFC) are elusive. Here, we examined the effects of the alpha(1)-AR agonist phenylephrine (Phe) on GABAergic transmission onto pyramidal neurons in the deep layers of the mPFC. We found that bath application of Phe dose-dependently increased the amplitude of evoked IPSCs (eIPSCs). Phe increased the frequency but not the amplitude of miniature IPSCs (mIPSCs). Ca2+ influx through T-type voltage-gated calcium channels is required for Phe-induced increases in GABA release. Phe increases GABA release probability and the number of releasable vesicles. Phe depolarizes the fast-spiking (FS) interneurons without effects on the firing rate of action potentials (APs) of interneurons. Phe-induced depolarization is independent of extracellular Na+, Ca2+ and T-type calcium channels, but requires inward rectifier K+ channels (Kirs). The present study demonstrates that Phe enhances GABAergic transmission onto mPFC pyramidal neurons through inhibiting interneurons Kirs, which further depolarizes interneurons leading to increase in Ca2+ influx via T-type calcium channels. Our results may provide a cellular and molecular mechanism that helps explain alpha(1)-AR-induced PFC dysfunction. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.