Department of Physiology, China Medical University, and Department of Rheuatology and Immunology, First Affiliated Hospital, Shenyang 110001, PR China.
Neuroscience. 2011 Jan 13;172:232-45. doi: 10.1016/j.neuroscience.2010.10.073. Epub 2010 Oct 31.
Systemic administration of salicylate at high doses can induce reversible tinnitus and hyperacusis in humans and animals. For this reason, a number of studies have investigated the salicylate-induced changes of neural activity in the auditory cortex (AC); however, most previous studies of the AC were conducted on brain slices or anesthetized animals, which cannot completely represent the actual conditions. Few efforts have been made to examine the neural activity of awake animals, and only recorded the local field potential (LFP) of the AC. In this study, we recorded neural spike activities from chronically implanted electrodes in the primary AC (A1) of awake cats, and investigated the changes of neural responses to pure-tone and click-train stimuli after systemic injection of 200 mg/kg salicylate. We found that sound-evoked spike activities were significantly increased from 1 h after salicylate administration, and the increase of neural responses lasted longer than 3 days with a peak at 12 h. Salicylate not only increased the amplitude of transient responses at the onset and offset of pure-tone stimuli, but also induced a sustained response during the prolonged stimulus period and a late response at ∼100 ms after stimulus offset. The significant enhancement of neural responses was observed over the entire tested frequency range (0.1-16 kHz) with a relative peak in the band of 3.2-9.6 kHz. The capability of exhibiting spikes synchronizing with successive clicks was also enhanced. All these effects were more apparent when the neurons were driven by high intensity sounds. Salicylate-administration also decreased the mean spontaneous rate in A1 units, and the decrease of spontaneous rate was larger in the units with a high initial spontaneous rate. Our data confirm that salicylate can modulate the neural activity at the cortical level and provide more information for understanding the mechanism of salicylate-induced tinnitus.
大剂量水杨酸盐全身给药可诱导人类和动物出现可逆性耳鸣和听觉过敏。出于这个原因，许多研究已经调查了水杨酸盐诱导的听觉皮层（AC）神经活动的变化；然而，以前对 AC 的大多数研究都是在脑切片或麻醉动物上进行的，这并不能完全代表实际情况。很少有研究致力于检查清醒动物的神经活动，并且仅记录了 AC 的局部场电位（LFP）。在这项研究中，我们从清醒猫的初级听觉皮层（A1）中慢性植入的电极记录神经尖峰活动，并研究了全身注射 200mg/kg 水杨酸盐后对纯音和 click-train 刺激的神经反应变化。我们发现，水杨酸盐给药后 1 小时，声音诱发的尖峰活动显著增加，神经反应的增加持续时间超过 3 天，在 12 小时达到峰值。水杨酸盐不仅增加了纯音刺激起始和结束时瞬态反应的幅度，而且在延长的刺激期间诱导了持续反应，并在刺激结束后约 100ms 时产生了晚期反应。在整个测试频率范围内（0.1-16kHz）都观察到了神经反应的显著增强，相对峰值出现在 3.2-9.6kHz 的频段。与连续 click 同步显示尖峰的能力也得到了增强。当神经元受到高强度声音的驱动时，所有这些效应都更加明显。水杨酸盐给药还降低了 A1 单位的平均自发率，并且初始自发率较高的单位的自发率下降更大。我们的数据证实水杨酸盐可以调节皮层水平的神经活动，并为理解水杨酸盐诱导的耳鸣机制提供了更多信息。
