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不同齿状回中间神经元类型的突触后 GABA 受体介导的电流。

Postsynaptic GABA-receptor mediated currents in diverse dentate gyrus interneuron types.

机构信息

Institute for Integrative Neuroanatomy, Charité-Universitätmedizin Berlin, Berlin, Germany.

Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.

出版信息

Hippocampus. 2024 Oct;34(10):551-562. doi: 10.1002/hipo.23628. Epub 2024 Aug 13.

Abstract

The processing of rich synaptic information in the dentate gyrus (DG) relies on a diverse population of inhibitory GABAergic interneurons to regulate cellular and circuit activity, in a layer-specific manner. Metabotropic GABA-receptors (GABARs) provide powerful inhibition to the DG circuit, on timescales consistent with behavior and learning, but their role in controlling the activity of interneurons is poorly understood with respect to identified cell types. We hypothesize that GABARs display cell type-specific heterogeneity in signaling strength, which will have direct ramifications for signal processing in DG networks. To test this, we perform in vitro whole-cell patch-clamp recordings from identified DG principal cells and interneurons, followed by GABAR pharmacology, photolysis of caged GABA, and extracellular stimulation of endogenous GABA release to classify the cell type-specific inhibitory potential. Based on our previous classification of DG interneurons, we show that postsynaptic GABAR-mediated currents are present on all interneuron types albeit at different amplitudes, dependent largely on soma location and synaptic targets. GABARs were coupled to inwardly-rectifying K+ channels that strongly reduced the excitability of those interneurons where large currents were observed. These data provide a systematic characterization of GABAR signaling in the rat DG to provide greater insight into circuit dynamics.

摘要

在齿状回(DG)中,丰富的突触信息处理依赖于多种抑制性 GABA 能中间神经元以层特异性的方式调节细胞和电路活动。代谢型 GABA 受体(GABARs)在与行为和学习一致的时间尺度上对 DG 电路提供强大的抑制作用,但它们在控制中间神经元活动方面的作用对于已鉴定的细胞类型知之甚少。我们假设 GABARs 在信号强度方面表现出细胞类型特异性的异质性,这将对 DG 网络中的信号处理产生直接影响。为了验证这一点,我们对鉴定的 DG 主细胞和中间神经元进行了体外全细胞膜片钳记录,然后进行 GABAR 药理学、笼形 GABA 的光解和内源性 GABA 释放的细胞外刺激,以对细胞类型特异性抑制潜能进行分类。根据我们以前对 DG 中间神经元的分类,我们表明,尽管幅度不同,但所有中间神经元类型都存在突触后 GABAR 介导的电流,这主要取决于胞体位置和突触靶点。GABAR 与内向整流 K+通道偶联,强烈降低了观察到大电流的中间神经元的兴奋性。这些数据对大鼠 DG 中的 GABAR 信号进行了系统表征,为深入了解电路动力学提供了更多的见解。

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