Dynamic Fidelity Control to the Central Auditory System: Synergistic Glycine/GABAergic Inhibition in the Cochlear Nucleus
Dynamic Fidelity Control to the Central Auditory System: Synergistic Glycine/GABAergic Inhibition in the Cochlear Nucleus
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DOI：
10.1523/jneurosci.0719-14.2014
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发表时间：
2014-08-27
影响因子：
5.3
通讯作者：
Milenkovic, Ivan
中科院分区：
文献类型：
--
作者：
Nerlich, Jana;Kuenzel, Thomas;Milenkovic, Ivan
GABA和甘氨酸是哺乳动物中枢神经系统中调节神经元活动的主要抑制递质。各自的递质在空间上大多是分开的，即前脑区的突触抑制是由GABA介导的，而甘氨酸主要用于脑干。因此，听觉脑干回路中的抑制在很大程度上是由甘氨酸介导的，但成熟时使用这两种递质的听觉突触很少。人们对这种双递质抑制机制的生理优势知之甚少。我们探讨了在幼年蒙古沙土鼠的听觉脑干中，甘氨酸和GABA在保持球状丛状细胞突触的终球上进行抑制的益处。这种模型突触能够通过系统声音刺激和对输入(保持的终球)输出(球形丛生细胞)功能的精确分析，在体内选择性地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显示，球形丛生细胞的动态AP抑制与甘氨酸-R和GABA(A)-R测定的抑制电导曲线密切相关。缓慢而有效的甘氨酸能成分主导抑制电导，因此主要解释了其高通滤波特性。GABA能传递以一种活性依赖的方式增强抑制强度和形成其持续时间，从而增加通过Hold的内球抑制兴奋的抑制效力。最后，在计算机模拟提供了体内和切片数据之间的强大联系，通过模拟在体内的自发和声音诱发的活动期间，在末端鳞茎和协同甘氨酸-GABA-电导之间的相互作用。
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 GABA(A)-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.