Inhibitory neurotransmission in animal models of tinnitus: maladaptive plasticity.
Inhibitory neurotransmission in animal models of tinnitus: maladaptive plasticity.
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DOI：
10.1016/j.heares.2011.04.004
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发表时间：
2011-09
期刊：
影响因子：
2.8
通讯作者：
Caspary, Donald M.
中科院分区：
文献类型：
--
作者：
Wang, Hongning;Brozoski, Thomas J.;Caspary, Donald M.
耳鸣是一种幻听，在美国有14%的人会有这种感觉，而生活质量下降的比例更小。一个令人信服的假设是，耳鸣的结果，从适应不良的塑料网下调抑制性氨基酸神经传递在中枢听觉通路。这种抑制的丧失可能是对传入输入丧失的补偿性反应，例如由声损伤和/或年龄相关的听力损失引起的，这是人们耳鸣的最常见原因。代偿性可塑性变化可能导致病理性神经活动，从而引起耳鸣。神经相关性包括自发发放增加、爆发增加和发放间期方差减少。本文将探讨慢性可塑性神经病变的证据，在中枢听觉系统的动物与精神病理学定义的耳鸣。神经化学研究将集中在可塑性耳鸣相关的变化抑制甘氨酸能神经传递在成年人耳蜗背核（DCN）。电生理学研究将集中在DCN和下丘（IC）的功能变化。耳鸣与DCN的主要输出神经元梭形细胞的自发活动增加和反应特性改变有关。与这些生理变化相一致的是甘氨酸受体（GlyR）亚基组成的变化，其锚定/运输蛋白，桥蛋白和膜GlyR的数量和亲和力的受体结合。在IC中，DCN梭形细胞的主要传入目标，在单位自发活动（率，爆发率，爆发模式）的多维变化被发现在动物的行为证据慢性耳鸣超过9个月后的声音/耳蜗侮辱。相反，紧接着一个强烈的声音曝光，IC自发活动的急性变化类似慢性耳鸣相关的变化，但不相同。这表明导致慢性耳鸣的长期神经可塑性变化可能是导致其持续存在的原因。对耳鸣相关的中枢听觉系统可塑性及其相关神经化学的清楚理解可能有助于确定治疗药物开发的独特靶点。
Tinnitus is a phantom auditory sensation experienced by up to 14% of the United States population with a smaller percentage experiencing decreased quality of life. A compelling hypothesis is that tinnitus results from a maladaptive plastic net down-regulation of inhibitory amino acid neurotransmission in the central auditory pathway. This loss of inhibition may be a compensatory response to loss of afferent input such as that caused by acoustic insult and/or age-related hearing loss, the most common causes of tinnitus in people. Compensatory plastic changes may result in pathologic neural activity that underpin tinnitus. The neural correlates include increased spontaneous spiking, increased bursting and decreased variance of inter-spike intervals. This review will examine evidence for chronic plastic neuropathic changes in the central auditory system of animals with psychophysically-defined tinnitus. Neurochemical studies will focus on plastic tinnitus-related changes of inhibitory glycinergic neurotransmission in the adult dorsal cochlear nucleus (DCN). Electrophysiological studies will focus on functional changes in the DCN and inferior colliculus (IC). Tinnitus was associated with increased spontaneous activity and altered response properties of fusiform cells, the major output neurons of DCN. Coincident with these physiologic alterations were changes in glycine receptor (GlyR) subunit composition, its anchoring/trafficking protein, gephyrin and the number and affinity of membrane GlyRs revealed by receptor binding. In the IC, the primary afferent target of DCN fusiform cells, multi-dimensional alterations in unit-spontaneous activity (rate, burst rate, bursting pattern) were found in animals with behavioral evidence of chronic tinnitus more than 9 months following the acoustic/cochlear insult. In contrast, immediately following an intense sound exposure, acute alterations in IC spontaneous activity resembled chronic tinnitus-related changes but were not identical. This suggests that long-term neuroplastic changes responsible for chronic tinnitus are likely to be responsible for its persistance. A clear understanding of tinnitus-related plasticity in the central auditory system and its associated neurochemistry may help define unique targets for therapeutic drug development.
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