Postsynaptic GABAB-receptor mediated currents in diverse dentate gyrus interneuron types

IF 2.4 3区 医学 Q3 NEUROSCIENCES Hippocampus Pub Date : 2024-08-13 DOI:10.1002/hipo.23628
Claudius E. Degro, Imre Vida, Sam A. Booker
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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 GABAB-receptors (GABABRs) 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 GABABRs 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 GABABR 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 GABABR-mediated currents are present on all interneuron types albeit at different amplitudes, dependent largely on soma location and synaptic targets. GABABRs 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 GABABR signaling in the rat DG to provide greater insight into circuit dynamics.

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不同类型齿状回中间神经元的突触后 GABAB 受体介导电流
齿状回(DG)对丰富突触信息的处理依赖于各种抑制性 GABA 能中间神经元,它们以层特异性的方式调节细胞和回路的活动。各向异性 GABAB 受体(GABABRs)为 DG 回路提供了强大的抑制作用,其时间尺度与行为和学习相一致,但对于它们在控制中间神经元活动中的作用,人们对已确定的细胞类型知之甚少。我们假设 GABABRs 在信号强度方面显示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。为了验证这一假设,我们对已确定的 DG 主细胞和中间神经元进行体外全细胞膜片钳记录,然后通过 GABABR 药理学、笼式 GABA 的光解和细胞外刺激内源性 GABA 释放来对细胞类型特异性抑制电位进行分类。根据我们之前对 DG 中间神经元的分类,我们发现突触后 GABABR 介导的电流存在于所有类型的中间神经元上,尽管幅度不同,但主要取决于体节位置和突触目标。GABABR 与内向纠偏 K+ 通道耦合,从而大大降低了观察到大电流的那些中间神经元的兴奋性。这些数据对大鼠DG中的GABABR信号传导进行了系统的描述,使人们对电路动力学有了更深入的了解。
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来源期刊
Hippocampus
Hippocampus 医学-神经科学
CiteScore
5.80
自引率
5.70%
发文量
79
审稿时长
3-8 weeks
期刊介绍: Hippocampus provides a forum for the exchange of current information between investigators interested in the neurobiology of the hippocampal formation and related structures. While the relationships of submitted papers to the hippocampal formation will be evaluated liberally, the substance of appropriate papers should deal with the hippocampal formation per se or with the interaction between the hippocampal formation and other brain regions. The scope of Hippocampus is wide: single and multidisciplinary experimental studies from all fields of basic science, theoretical papers, papers dealing with hippocampal preparations as models for understanding the central nervous system, and clinical studies will be considered for publication. The Editor especially encourages the submission of papers that contribute to a functional understanding of the hippocampal formation.
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