Ionic Mechanisms Involved in β3-Adrenoceptor-Mediated Augmentation of GABAergic Transmission Onto Pyramidal Neurons in Prefrontal Cortex

IF 4.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Neurochemistry Pub Date : 2025-01-27 DOI:10.1111/jnc.70005

Fei Luo, Jian Zheng, Wei-ke Deng

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Abstract

Activation of the brain-penetrant beta3-adrenergic receptor (Adrb3) is implicated in the treatment of depressive disorders. Enhancing GABAergic inputs from interneurons onto pyramidal cells of prefrontal cortex (PFC) represents a strategy for antidepressant therapies. Here, we probed the effects of the activation of Adrb3 on GABAergic transmission onto pyramidal neurons in the PFC using in vitro electrophysiology. We found that Adrb3 agonist SR58611A increased both the frequency and the amplitude of miniature IPSCs (mIPSCs). Ca²⁺ influx through T-type voltage-gated Ca²⁺ channel (T-type VGCC) contributed to SR58611A-enhanced mIPSC frequency. We also found that SR58611A facilitated GABA release probability and the number of releasable vesicles through interaction with T-type VGCC. SR58611A depolarized somatostatin (Sst) interneurons with no effects on the firing rate of action potential of Sst interneurons. SR58611A-induced depolarization of Sst interneurons and enhancement of mIPSC frequency required inward rectifier K⁺ channel (Kir). Our results suggest that Kir and T-type VGCC in Sst interneurons participate in SR58611A-induced increase in GABA release in PFC.

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参与β3-肾上腺素受体介导的 GABA 能向前额叶皮层锥体神经元传导增强的离子机制

激活大脑中的β3-肾上腺素能受体（Adrb3）与抑郁症的治疗有关。增强从中间神经元到前额叶皮质锥体细胞的 GABA 能输入是抗抑郁疗法的一种策略。在这里，我们使用体外电生理学方法探究了激活 Adrb3 对 GABA 能向前额叶皮质锥体神经元传递的影响。我们发现 Adrb3 激动剂 SR58611A 增加了微型 IPSCs（mIPSCs）的频率和振幅。通过T型电压门控Ca2+通道（T型VGCC）流入的Ca2+促成了SR58611A增强的mIPSC频率。我们还发现，SR58611A 通过与 T 型 VGCC 相互作用，促进了 GABA 的释放概率和可释放囊泡的数量。SR58611A 使体泌素（Sst）中间神经元去极化，但对 Sst 中间神经元动作电位的发射率没有影响。SR58611A 诱导的 Sst 神经元去极化和 mIPSC 频率的增强需要内向整流 K+ 通道（Kir）。我们的结果表明，Sst 中间神经元中的 Kir 和 T 型 VGCC 参与了 SR58611A 诱导的 PFC GABA 释放增加。

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来源期刊

Journal of Neurochemistry 医学-神经科学

CiteScore

9.30

自引率

2.10%

发文量

181

审稿时长

2.2 months

期刊介绍： Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.