Plastic changes along auditory pathway during salicylate-induced ototoxicity: Hyperactivity and CF shifts.
Plastic changes along auditory pathway during salicylate-induced ototoxicity: Hyperactivity and CF shifts.
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DOI：
10.1016/j.heares.2016.10.021
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发表时间：
2017-04
期刊：
影响因子：
2.8
通讯作者：
Salvi R
中科院分区：
文献类型：
--
作者：
Jiang C;Luo B;Manohar S;Chen GD;Salvi R
高剂量的水杨酸，阿司匹林的活性成分，长期以来一直被认为会导致短暂性听力丧失，耳鸣和听觉亢进，这使它成为一个强有力的实验工具。这些水杨酸引起的知觉障碍与耳蜗神经输出的大量减少有关。矛盾的是，耳蜗神经输出的减少伴随着听觉皮层（AC）和中枢神经系统其他部分的声音诱发活动的急剧增加。神经活动的增加究竟是从哪里开始的，并沿着中央听觉通路积累起来的，目前还不完全清楚。为了解决这个问题，我们测量了高剂量水杨酸钠（SS, 300 mg/kg）前后耳蜗、耳蜗核（CN）、下丘（IC）和耳蜗AC的声诱发神经活动。ss处理消除了沿听觉通路的低水平声音诱发反应，导致20-30 dB阈值移位。虽然在高强度下耳蜗的神经输出量明显减少，但神经中枢的神经反应仅轻微减少；中枢性脑区几乎正常或略有增强，而中枢性脑区明显增强，表明中央增益进展增加。ss引起的中音区和中音区中枢反应的增加与频率有关，其中最大的增加发生在中频范围内，即ss引起耳鸣的假定音高。这种频率依赖性的过度活跃似乎是由频率接受野（FRF）的移位引起的，这样许多FRF的响应区域向中频移动/扩展。我们的结果表明，ss诱导的阈值移位起源于耳蜗。相反，中枢增益的增强并不局限于一个区域，而是通过抑制的丧失和/或兴奋的增加，在听觉通路的连续更高阶段逐步建立起来。
High dose of salicylate, the active ingredient in aspirin, has long been known to induce transient hearing loss, tinnitus and hyperacusis making it a powerful experimental tool. These salicylate-induced perceptual disturbances are associated with a massive reduction in the neural output of the cochlea. Paradoxically, the diminished neural output of the cochlea is accompanied by a dramatic increase in sound-evoked activity in the auditory cortex (AC) and several other parts of the central nervous system. Exactly where the increase in neural activity begins and builds up along the central auditory pathway are not fully understood. To address this issue, we measured sound-evoked neural activity in the cochlea, cochlear nucleus (CN), inferior colliculus (IC), and AC before and after administering a high dose of sodium salicylate (SS, 300 mg/kg). The SS-treatment abolished low-level sound-evoked responses along the auditory pathway resulting in a 20–30 dB threshold shift. While the neural output of the cochlea was substantially reduced at high intensities, the neural responses in the CN were only slightly reduced; those in the IC were nearly normal or slightly enhanced while those in the AC considerably enhanced, indicative of a progress increase in central gain. The SS-induced increase in central response in the IC and AC was frequency-dependent with the greatest increase occurring in the mid-frequency range the putative pitch of SS-induced tinnitus. This frequency-dependent hyperactivity appeared to result from shifts in the frequency receptive fields (FRF) such that the response areas of many FRF shifted/expanded toward the mid-frequencies. Our results suggest that the SS-induced threshold shift originates in the cochlea. In contrast, enhanced central gain is not localized to one region, but progressively builds up at successively higher stage of the auditory pathway either through a loss of inhibition and/or increased excitation.