关键词: GABAB receptors dentate gyrus inhibition interneuron

来  源:   DOI:10.1002/hipo.23628

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.
摘要:
齿状回(DG)中丰富的突触信息的处理依赖于不同群体的抑制性GABA能中间神经元来调节细胞和回路活动,以特定于图层的方式。代谢型GABAB受体(GABABR)对DG回路提供了强大的抑制作用,在与行为和学习一致的时间尺度上,但是它们在控制中间神经元活动中的作用在确定的细胞类型方面知之甚少。我们假设GABABRs在信号强度方面表现出细胞类型特异性异质性,这将对DG网络中的信号处理产生直接影响。为了测试这个,我们从确定的DG主细胞和中间神经元进行体外全细胞膜片钳记录,其次是GABABR药理学,笼状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力进行分类。根据我们以前对DG中间神经元的分类,我们表明,突触后GABABR介导的电流存在于所有中间神经元类型,尽管在不同的幅度,很大程度上取决于体细胞的位置和突触的目标。GABABR与向内整流的K通道偶联,从而大大降低了观察到大电流的中间神经元的兴奋性。这些数据提供了大鼠DG中GABABR信号传导的系统表征,以提供对回路动力学的更深入了解。
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