Hockley Adam, Berger Joel I, Palmer Alan R, Wallace Mark N
Medical Research Council Institute of Hearing Research, School of Medicine, University of Nottingham, Nottingham, UK.
School of Life Sciences, University of Nottingham, Nottingham, UK.
Eur J Neurosci. 2020 Nov;52(9):4057-4080. doi: 10.1111/ejn.14913. Epub 2020 Aug 1.
Previous work has led to the hypothesis that, during the production of noise-induced tinnitus, higher levels of nitric oxide (NO), in the ventral cochlear nucleus (VCN), increase the gain applied to a reduced input from the cochlea. To test this hypothesis, we noise-exposed 26 guinea pigs, identified evidence of tinnitus in 12 of them and then compared the effects of an iontophoretically applied NO donor or production inhibitor on VCN single unit activity. We confirmed that the mean driven firing rate for the tinnitus and control groups was the same while it had fallen in the non-tinnitus group. By contrast, the mean spontaneous rate had increased for the tinnitus group relative to the control group, while it remained the same for the non-tinnitus group. A greater proportion of units responded to exogenously applied NO in the tinnitus (56%) and non-tinnitus groups (71%) than a control population (24%). In the tinnitus group, endogenous NO facilitated the driven firing rate in 37% (7/19) of neurons and appeared to bring the mean driven rate back up to control levels by a mechanism involving N-methyl-D-aspartic acid (NMDA) receptors. By contrast, in the non-tinnitus group, endogenous NO only facilitated the driven firing rate in 5% (1/22) of neurons and there was no facilitation of driven rate in the control group. The effects of endogenous NO on spontaneous activity were unclear. These results suggest that NO is involved in increasing the gain applied to driven activity, but other factors are also involved in the increase in spontaneous activity.
在噪声性耳鸣产生过程中，耳蜗腹侧核（VCN）中较高水平的一氧化氮（NO）会增加对来自耳蜗减少的输入所施加的增益。为了验证这一假设，我们让26只豚鼠暴露于噪声环境中，在其中12只中确定了耳鸣的证据，然后比较了离子电渗法应用的NO供体或产生抑制剂对VCN单个单位活动的影响。我们证实，耳鸣组和对照组的平均驱动放电率相同，而非耳鸣组的平均驱动放电率下降。相比之下，耳鸣组的平均自发率相对于对照组有所增加，而非耳鸣组的平均自发率保持不变。与对照组（24%）相比，耳鸣组（56%）和非耳鸣组（71%）中有更大比例的单位对外源性应用的NO有反应。在耳鸣组中，内源性NO促进了37%（7/19）神经元的驱动放电率，并且似乎通过一种涉及N-甲基-D-天冬氨酸（NMDA）受体的机制使平均驱动率恢复到对照水平。相比之下，在非耳鸣组中，内源性NO仅促进了5%（1/22）神经元的驱动放电率，而对照组中驱动率没有促进作用。内源性NO对自发活动的影响尚不清楚。这些结果表明，NO参与增加对驱动活动所施加的增益，但其他因素也参与了自发活动的增加。
