Physiology, School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Crawley, WA, Australia.
Eur J Neurosci. 2010 May;31(9):1616-28. doi: 10.1111/j.1460-9568.2010.07183.x.
Hearing loss from acoustic trauma is a risk factor for tinnitus. Animal models using acoustic trauma have demonstrated hyperactivity in central auditory pathways, which has been suggested as a substrate for tinnitus. We used a guinea-pig model of unilateral acoustic trauma. Within the same animals, measurements of peripheral hearing loss, spontaneous activity of single neurons in the inferior colliculus and gene expression in cochlear nucleus and inferior colliculus were combined, acutely and after recovery from acoustic trauma. Genes investigated related to inhibitory (GABA-A receptor subunit alpha 1; glycine receptor subunit alpha 1) and excitatory neurotransmission (glutamate decarboxylase 1; glutamate receptor AMPA subunit alpha 2; glutamate receptor NMDA subunit 1), regulation of transmitter release (member of RAB family of small GTPase; RAB3 GTPase activating protein subunit 1) and neuronal excitability (potassium channel subfamily K member 15). Acoustic trauma resulted in unilateral hearing loss and hyperactivity bilaterally in inferior colliculus. Changes in expression of different mRNAs were observed in ipsilateral cochlear nucleus and in ipsi- and contralateral inferior colliculus, immediately after acoustic trauma, and after 2 and 4 weeks' recovery. Gene expression was generally reduced immediately after trauma, followed by a return to near normal levels or over-expression as recovery time increased. Different mechanisms appear to underlie the spontaneous hyperactivity observed. There is evidence of down-regulation of genes associated with neuronal inhibition in the contralateral inferior colliculus, whereas in ipsilateral cochlear nucleus, competing actions of inhibitory and excitatory systems seem to play a major role in determining overall excitability.
听力损失是由声创伤引起的，是耳鸣的一个风险因素。使用声创伤的动物模型表明，中枢听觉通路的过度活跃，这被认为是耳鸣的一个基础。我们使用了单侧声创伤的豚鼠模型。在相同的动物中，结合了外周听力损失的测量、下丘单个神经元的自发活动以及耳蜗核和下丘的基因表达，在急性和从声创伤恢复后进行了测量。研究的与抑制性（GABA-A 受体亚单位 alpha 1；甘氨酸受体亚单位 alpha 1）和兴奋性神经传递（谷氨酸脱羧酶 1；谷氨酸受体 AMPA 亚单位 alpha 2；谷氨酸受体 NMDA 亚单位 1）、递质释放调节（RAB 家族小 GTPase 成员；RAB3 GTPase 激活蛋白亚单位 1）和神经元兴奋性（钾通道亚家族 K 成员 15）相关的基因。声创伤导致单侧听力损失和双侧下丘的过度活跃。在声创伤后立即和 2 周和 4 周恢复后，观察到同侧耳蜗核和同侧和对侧下丘中不同 mRNA 的表达变化。基因表达通常在创伤后立即减少，随后随着恢复时间的增加而恢复到接近正常水平或过度表达。观察到的自发性过度活跃似乎有不同的机制。有证据表明，在对侧下丘中与神经元抑制相关的基因下调，而在同侧耳蜗核中，抑制性和兴奋性系统的竞争作用似乎在决定整体兴奋性方面起着主要作用。
