Southern Illinois University School of Medicine, Department of Pharmacology, Springfield, Illinois; and.
J Neurophysiol. 2014 Jan;111(2):229-38. doi: 10.1152/jn.00556.2013. Epub 2013 Oct 23.
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central auditory system. Sensory thalamic structures show high levels of non-desensitizing extrasynaptic GABAA receptors (GABAARs) and a reduction in the redundancy of coded information. The present study compared the inhibitory potency of GABA acting at GABAARs between the inferior colliculus (IC) and the medial geniculate body (MGB) using quantitative in vivo, in vitro, and ex vivo experimental approaches. In vivo single unit studies compared the ability of half maximal inhibitory concentrations of GABA to inhibit sound-evoked temporal responses, and found that GABA was two to three times (P < 0.01) more potent at suppressing MGB single unit responses than IC unit responses. In vitro whole cell patch-clamp slice recordings were used to demonstrate that gaboxadol, a δ-subunit selective GABAAR agonist, was significantly more potent at evoking tonic inhibitory currents from MGB neurons than IC neurons (P < 0.01). These electrophysiological findings were supported by an in vitro receptor binding assay which used the picrotoxin analog [(3)H]TBOB to assess binding in the GABAAR chloride channel. MGB GABAARs had significantly greater total open chloride channel capacity relative to GABAARs in IC (P < 0.05) as shown by increased total [(3)H]TBOB binding. Finally, a comparative ex vivo measurement compared endogenous GABA levels and suggested a trend towards higher GABA concentrations in MGB than in IC. Collectively, these studies suggest that, per unit GABA, high affinity extrasynaptic and synaptic GABAARs confer a significant inhibitory GABAAR advantage to MGB neurons relative to IC neurons. This increased GABA sensitivity likely underpins the vital filtering role of auditory thalamus.
γ-氨基丁酸（GABA）是中枢听觉系统中的主要抑制性神经递质。感觉丘脑结构显示高水平的非脱敏型突触外 GABAA 受体（GABAAR）和编码信息冗余度降低。本研究采用定量活体、体外和离体实验方法，比较了下丘（IC）和内侧膝状体（MGB）中 GABA 作用于 GABAAR 的抑制效力。在体内单细胞研究中比较了 GABA 的半最大抑制浓度抑制声音诱发的时间反应的能力，发现 GABA 抑制 MGB 单细胞反应的效力比 IC 单细胞反应高 2 到 3 倍（P < 0.01）。体外全细胞膜片钳切片记录用于证明，gaboxadol 是一种 δ-亚基选择性 GABAAR 激动剂，比 IC 神经元更有效地从 MGB 神经元中引发紧张性抑制电流（P < 0.01）。这些电生理发现得到了体外受体结合测定的支持，该测定使用了 picrotoxin 类似物 [3H]TBOB 来评估 GABAAR 氯通道中的结合。与 IC 中的 GABAAR 相比，MGB 中的 GABAAR 具有更大的总开放氯通道容量（P < 0.05），表现为总 [3H]TBOB 结合增加。最后，一项比较性离体测量比较了内源性 GABA 水平，并表明 MGB 中的 GABA 浓度比 IC 中呈上升趋势。总之，这些研究表明，与 GABA 相比，每单位 GABA 中，高亲和力的突触外和突触型 GABAAR 赋予 MGB 神经元相对于 IC 神经元显著的抑制性 GABAAR 优势。这种增加的 GABA 敏感性可能是听觉丘脑重要过滤作用的基础。
