双极耳蜗内电刺激诱发的听觉脑干中Fos样免疫反应:电流水平和脉冲持续时间的影响。
Fos-like immunoreactivity in the auditory brainstem evoked by bipolar intracochlear electrical stimulation: effects of current level and pulse duration.
作者信息
Saito H, Miller J M, Pfingst B E, Altschuler R A
机构信息
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan Medical Center, Ann Arbor 48109-0506, USA.
出版信息
Neuroscience. 1999;91(1):139-61. doi: 10.1016/s0306-4522(98)00581-8.
Fos-like immunoreactivity was used to compare the auditory brain stem excitation elicited by bipolar electrical stimulation of the cochlea at various current levels relative to the electrically evoked auditory brain stem response threshold for a 50-micros/phase monophasic pulse. Fos-like immunoreactive cells were labeled in primary auditory brain stem regions. The distribution of labeled cells was restricted to regions known to be cochleotopically related to the stimulated region of the scala tympani. Some labeled cells were observed at 2x electrically evoked auditory brain stem response threshold. The number, density and spatial distribution of labeled cells were quantified in the dorsal cochlear nucleus and inferior colliculus, and found to increase with increasing level of stimulation. For 50-micros pulses, the location of labeled neurons remained reasonably restricted to narrow bands within each region until the 1Ox level of stimulation (20 dB above electrically evoked auditory brain stem response threshold) was reached. While a monotonic increase in Fos-like immunoreactivity with increasing stimulus level was observed in most nuclei, for cells of the superficial layer of the dorsal cochlear nucleus, a non-monotonic change with increasing stimulus level was seen. This dorsal cochlear nucleus non-monotonicity may indicate that, at higher levels of stimulation, a secondary indirect inhibitory input, probably associated with activation of deep layer dorsal cochlear nucleus cells, reduces excitatory responses at the superficial layer of the dorsal cochlear nucleus. Electrically evoked auditory brain stem response and Fos expression showed parallel changes as a function of stimulus level and pulse duration. The data indicate that discrete activation of cell populations within the central auditory pathways can occur with bipolar electrical stimulation to the highest levels of stimulation typically useful in humans. The data also indicate a close, but not identical, quantitative relationship between Fos-like immunoreactivity and electrophysiological response amplitude. These findings support the view that a study of Fos-like immunoreactivity can provide a powerful and quantitative tool for study of the dynamic response characteristics of cells of the central auditory system to electrical stimulation at suprathreshold levels. The data suggest that there is a monotonic increase in the number of neurons responsive to intracochlear electrical stimulation as a function of stimulus level, at least through the upper half of the dynamic range, but that this increase does not result in a complete loss of spatial selectivity. Coupled with previous psychophysical studies, these results suggest that the increase in the number of activated neurons is functionally beneficial, resulting in improved discrimination of changes in the electrical signals.
采用Fos样免疫反应性,比较在不同电流水平下,相对于50微秒/相位单相脉冲的电诱发听性脑干反应阈值,耳蜗双极电刺激所引发的听性脑干兴奋情况。在听性脑干的主要区域标记出Fos样免疫反应性细胞。标记细胞的分布局限于已知与鼓阶受刺激区域呈耳蜗拓扑学相关的区域。在2倍电诱发听性脑干反应阈值时观察到一些标记细胞。对背侧耳蜗核和下丘中标记细胞的数量、密度及空间分布进行量化,发现其随刺激水平的升高而增加。对于50微秒的脉冲,在达到10倍刺激水平(比电诱发听性脑干反应阈值高20分贝)之前,标记神经元的位置合理地局限于每个区域内的窄带。虽然在大多数核中观察到Fos样免疫反应性随刺激水平升高呈单调增加,但对于背侧耳蜗核浅层的细胞,可见其随刺激水平升高呈非单调变化。背侧耳蜗核的这种非单调性可能表明,在较高刺激水平时,一种可能与深层背侧耳蜗核细胞激活相关的继发性间接抑制性输入,会降低背侧耳蜗核浅层的兴奋性反应。电诱发听性脑干反应和Fos表达随刺激水平和脉冲持续时间呈现平行变化。数据表明,对人类通常有用的最高刺激水平进行双极电刺激时,可在中枢听觉通路内发生细胞群的离散激活。数据还表明Fos样免疫反应性与电生理反应幅度之间存在密切但不完全相同的定量关系。这些发现支持这样一种观点,即对Fos样免疫反应性的研究可为研究中枢听觉系统细胞对阈上水平电刺激的动态反应特性提供一种强大的定量工具。数据表明,至少在动态范围的上半部分,对蜗内电刺激有反应的神经元数量随刺激水平呈单调增加,但这种增加不会导致空间选择性完全丧失。结合先前的心理物理学研究,这些结果表明激活神经元数量的增加在功能上是有益的,可改善对电信号变化的辨别。