Division of Otolaryngology, Southern Illinois University School of Medicine, Springfield IL, USA.
Front Syst Neurosci. 2012 Feb 24;6:9. doi: 10.3389/fnsys.2012.00009. eCollection 2012.
Damage to the auditory system following high-level sound exposure reduces afferent input. Homeostatic mechanisms appear to compensate for the loss. Overcompensation may produce the sensation of sound without an objective physical correlate, i.e., tinnitus. Several potential compensatory neural processes have been identified, such as increased spontaneous activity. The cellular mechanisms enabling such compensatory processes may involve down-regulation of inhibitory neurotransmission mediated by γ-amino butyric acid (GABA), and/or up-regulation of excitatory neurotransmission, mediated by glutamic acid (Glu). Because central processing systems are integrated and well-regulated, compensatory changes in one system may produce reactive changes in others. Some or all may be relevant to tinnitus. To examine the roles of GABA and Glu in tinnitus, high resolution point-resolved proton magnetic resonance spectroscopy ((1)H-MRS) was used to quantify their levels in the dorsal cochlear nucleus (DCN), inferior colliculus (IC), medial geniculate body (MGB), and primary auditory cortex (A1) of rats. Chronic tinnitus was produced by a single high-level unilateral exposure to noise, and was measured using a psychophysical procedure sensitive to tinnitus. Decreased GABA levels were evident only in the MGB, with the greatest decrease, relative to unexposed controls, obtained in the contralateral MGB. Small GABA increases may have been present bilaterally in A1 and in the contralateral DCN. Although Glu levels showed considerable variation, Glu was moderately and bilaterally elevated both in the DCN and in A1. In the MGB Glu was increased ipsilaterally but decreased contralaterally. These bidirectional and region-specific alterations in GABA and Glu may reflect large-scale changes in inhibitory and excitatory equilibrium accompanying chronic tinnitus. The present results also suggest that targeting both neurotransmitter systems may be optimal in developing more effective therapeutics.
高电平声音暴露后听觉系统的损伤会减少传入输入。稳态机制似乎可以补偿这种损失。过度补偿可能会产生没有客观物理关联的声音感觉，即耳鸣。已经确定了几种潜在的代偿性神经过程，例如自发性活动增加。使这种代偿过程成为可能的细胞机制可能涉及γ-氨基丁酸（GABA）介导的抑制性神经传递的下调，和/或谷氨酸（Glu）介导的兴奋性神经传递的上调。由于中枢处理系统是集成和良好调节的，一个系统中的代偿变化可能会在其他系统中产生反应性变化。有些或全部可能与耳鸣有关。为了研究 GABA 和 Glu 在耳鸣中的作用，使用高分辨率点分辨质子磁共振波谱（1H-MRS）来定量测量大鼠耳蜗背核（DCN）、下丘（IC）、内侧膝状体（MGB）和初级听觉皮层（A1）中它们的水平。通过单次高水平单侧噪声暴露产生慢性耳鸣，并使用对耳鸣敏感的心理物理程序进行测量。仅在 MGB 中可见 GABA 水平降低，与未暴露的对照组相比，对侧 MGB 的降低最为明显。双侧 A1 和对侧 DCN 可能存在小的 GABA 增加。尽管 Glu 水平变化很大，但 Glu 在 DCN 和 A1 中均适度且双侧升高。在 MGB 中，Glu 同侧增加而对侧减少。GABA 和 Glu 的这种双向和区域特异性改变可能反映了慢性耳鸣伴随的抑制性和兴奋性平衡的大规模变化。目前的结果还表明，靶向这两种神经递质系统可能是开发更有效治疗方法的最佳选择。
