Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, 04103 Leipzig, Germany.
Institute of Biology 2, RWTH Aachen University, 52062 Aachen, Germany.
J Neurosci. 2014 Aug 27;34(35):11604-20. doi: 10.1523/JNEUROSCI.0719-14.2014.
GABA and glycine are the major inhibitory transmitters that attune neuronal activity in the CNS of mammals. The respective transmitters are mostly spatially separated, that is, synaptic inhibition in the forebrain areas is mediated by GABA, whereas glycine is predominantly used in the brainstem. Accordingly, inhibition in auditory brainstem circuits is largely mediated by glycine, but there are few auditory synapses using both transmitters in maturity. Little is known about physiological advantages of such a two-transmitter inhibitory mechanism. We explored the benefit of engaging both glycine and GABA with inhibition at the endbulb of Held-spherical bushy cell synapse in the auditory brainstem of juvenile Mongolian gerbils. This model synapse enables selective in vivo activation of excitatory and inhibitory neuronal inputs through systemic sound stimulation and precise analysis of the input (endbulb of Held) output (spherical bushy cell) function. The combination of in vivo and slice electrophysiology revealed that the dynamic AP inhibition in spherical bushy cells closely matches the inhibitory conductance profile determined by the glycine-R and GABAA-R. The slow and potent glycinergic component dominates the inhibitory conductance, thereby primarily accounting for its high-pass filter properties. GABAergic transmission enhances the inhibitory strength and shapes its duration in an activity-dependent manner, thus increasing the inhibitory potency to suppress the excitation through the endbulb of Held. Finally, in silico modeling provides a strong link between in vivo and slice data by simulating the interactions between the endbulb- and the synergistic glycine-GABA-conductances during in vivo-like spontaneous and sound evoked activities.
GABA 和甘氨酸是调节哺乳动物中枢神经系统神经元活动的主要抑制性递质。相应的递质在空间上大多是分离的，即前脑区域的突触抑制由 GABA 介导，而甘氨酸主要用于脑干。因此，听觉脑干回路的抑制主要由甘氨酸介导，但在成熟过程中很少有听觉突触同时使用这两种递质。对于这种双递质抑制机制的生理优势知之甚少。我们在幼年蒙古沙鼠听觉脑干的终球 - 球形布什细胞突触处的研究了抑制作用中同时使用甘氨酸和 GABA 的益处。该模型突触允许通过全身声音刺激和对输入（终球）输出（球形布什细胞）功能的精确分析，选择性地在体内激活兴奋性和抑制性神经元输入。体内和切片电生理学的结合表明，球形布什细胞中的动态 AP 抑制与甘氨酸-R 和 GABAA-R 确定的抑制性电导谱密切匹配。快速且有力的甘氨酸能成分主导抑制性电导，从而主要解释了其高通滤波器特性。GABA 能传递增强抑制强度并以活动依赖性方式塑造其持续时间，从而通过终球增加抑制兴奋的能力。最后，在体内样自发和声音诱发活动期间模拟终球和协同甘氨酸-GABA 电导之间的相互作用，为体内和切片数据之间提供了强有力的联系。
