Schaette Roland, Kempter Richard
Department of Biology, Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Invalidenstr. 43, 10115 Berlin, Germany.
Eur J Neurosci. 2006 Jun;23(11):3124-38. doi: 10.1111/j.1460-9568.2006.04774.x.
Tinnitus, the perception of a sound in the absence of acoustic stimulation, is often associated with hearing loss. Animal studies indicate that hearing loss through cochlear damage can lead to behavioral signs of tinnitus that are correlated with pathologically increased spontaneous firing rates, or hyperactivity, of neurons in the auditory pathway. Mechanisms that lead to the development of this hyperactivity, however, have remained unclear. We address this question by using a computational model of auditory nerve fibers and downstream auditory neurons. The key idea is that mean firing rates of these neurons are stabilized through a homeostatic plasticity mechanism. This homeostatic compensation can give rise to hyperactivity in the model neurons if the healthy ratio between mean and spontaneous firing rate of the auditory nerve is decreased, for example through a loss of outer hair cells or damage to hair cell stereocilia. Homeostasis can also amplify non-auditory inputs, which then contribute to hyperactivity. Our computational model predicts how appropriate additional acoustic stimulation can reverse the development of such hyperactivity, which could provide a new basis for treatment strategies.
耳鸣，即在没有声音刺激时感觉到声音，通常与听力损失有关。动物研究表明，耳蜗损伤导致的听力损失会引发耳鸣的行为迹象，这与听觉通路中神经元病理性增加的自发放电率或活动亢进有关。然而，导致这种活动亢进发展的机制仍不清楚。我们通过使用听觉神经纤维和下游听觉神经元的计算模型来解决这个问题。关键思想是这些神经元的平均放电率通过一种稳态可塑性机制得以稳定。如果听觉神经的平均放电率与自发放电率之间的健康比例降低，例如通过外毛细胞损失或毛细胞静纤毛损伤，这种稳态补偿会导致模型神经元出现活动亢进。稳态还可以放大非听觉输入，进而导致活动亢进。我们的计算模型预测了适当的额外声音刺激如何能够逆转这种活动亢进的发展，这可能为治疗策略提供新的基础。
