Neurobiology Laboratory, Division of Neurobiology, Faculty of Biology, Ludwig Maximilian University of Munich, Munich, Germany.
Auditory Neurophysiology Laboratory, Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester, United Kingdom.
Front Neural Circuits. 2021 Oct 12;15:759342. doi: 10.3389/fncir.2021.759342. eCollection 2021.
Nitric oxide (NO) is of fundamental importance in regulating immune, cardiovascular, reproductive, neuromuscular, and nervous system function. It is rapidly synthesized and cannot be confined, it is highly reactive, so its lifetime is measured in seconds. These distinctive properties (contrasting with classical neurotransmitters and neuromodulators) give rise to the concept of NO as a "volume transmitter," where it is generated from an active source, diffuses to interact with proteins and receptors within a sphere of influence or volume, but limited in distance and time by its short half-life. In the auditory system, the neuronal NO-synthetizing enzyme, nNOS, is highly expressed and tightly coupled to postsynaptic calcium influx at excitatory synapses. This provides a powerful activity-dependent control of postsynaptic intrinsic excitability via cGMP generation, protein kinase G activation and modulation of voltage-gated conductances. NO may also regulate vesicle mobility via retrograde signaling. This Mini Review focuses on the auditory system, but highlights general mechanisms by which NO mediates neuronal intrinsic plasticity and synaptic transmission. The dependence of NO generation on synaptic and sound-evoked activity has important local modulatory actions and NO serves as a "volume transmitter" in the auditory brainstem. It also has potentially destructive consequences during intense activity or on spill-over from other NO sources during pathological conditions, when aberrant signaling may interfere with the precisely timed and tonotopically organized auditory system.
一氧化氮（NO）在调节免疫、心血管、生殖、神经肌肉和神经系统功能方面具有重要意义。它的合成速度很快，不能被局限，而且具有高度的反应性，因此其寿命以秒来衡量。这些独特的特性（与经典的神经递质和神经调质形成对比）使得 NO 被认为是一种“容积递质”，即它从活跃的源头产生，扩散到影响或容积范围内与蛋白质和受体相互作用，但由于半衰期短，其距离和时间有限。在听觉系统中，神经元一氧化氮合成酶，nNOS，高度表达，并与兴奋性突触后钙离子内流紧密偶联。这通过 cGMP 的产生、蛋白激酶 G 的激活以及电压门控电流的调制，为突触后固有兴奋性提供了一种强大的、依赖于活动的控制。NO 也可以通过逆行信号来调节囊泡的流动性。本综述重点关注听觉系统，但强调了 NO 介导神经元固有可塑性和突触传递的一般机制。NO 的产生对突触和声音诱发活动的依赖性具有重要的局部调制作用，并且作为听觉脑干中的“容积递质”。在强烈的活动期间，或者在病理条件下，来自其他 NO 源的溢出期间，NO 可能具有潜在的破坏性后果，此时异常信号可能干扰精确定时和音高组织的听觉系统。
