Axonal Sodium-Channel Bands Shape the Response to Electric Stimulation in Retinal Ganglion Cells
Axonal Sodium-Channel Bands Shape the Response to Electric Stimulation in Retinal Ganglion Cells
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DOI：
10.1152/jn.91081.2008
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发表时间：
2009-04-01
影响因子：
2.5
通讯作者：
Rizzo, Joseph F., III
中科院分区：
文献类型：
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作者：
Fried, Shelley I.;Lasker, Aaron C. W.;Rizzo, Joseph F., III
3 . Fried SI, Lasker ACW, Desai NJ, Eddington DK, Rizzo JF。轴突钠通道带形成视网膜神经节细胞对电刺激的反应。中国生物医学工程学报（英文版），2009。2009年2月4日首次发表；doi: 10.1152 / jn.91081.2008。视网膜的电刺激可靠地引起了因视网膜外疾病致盲的患者的光感知。然而，个体感知是高度可变的，不容易组合成更复杂的视觉图像。因此，传达给患者的视觉信息质量相当有限。为了开发更有效的刺激方法，从而改善心理物理结果，我们正在研究视网膜神经元如何对电刺激作出反应。视网膜的情况类似于其他神经义肢的应用，其中更好地了解潜在的神经反应可能会导致改善的临床结果。在这里，我们确定了视网膜神经节细胞中哪个元素具有启动动作电位的最低阈值。先前的研究提出了多种可能性，尽管所有可能性都在体细胞/近端轴突区域。为了确定实际位置，我们在兔神经节细胞的体细胞/近端轴突区域周围的密集二维网格中测量阈值。在定向选择性（DS）神经节细胞中，最低阈值位于轴突的一小部分，距离体细胞约40 μ m。免疫化学染色显示以同一位置为中心的密集电压门控钠通道带，表明刺激电极离钠通道带最近时阈值最低。低阈区域的大小和位置在DS细胞内是一致的，但在其他神经节细胞类型中有所不同。类似地，钠离子通道带的长度和位置也因细胞类型而异。与波段性质的差异一致，我们发现不同细胞类型的绝对（最低）阈值也不同。综上所述，我们的研究结果表明，钠通道带是对电刺激最敏感的部位，而这些带的差异是我们观察到的阈值差异的基础。
Fried SI, Lasker ACW, Desai NJ, Eddington DK, Rizzo JF 3rd. Axonal sodium-channel bands shape the response to electric stimulation in retinal ganglion cells. J Neurophysiol 101: 1972-1987, 2009. First published February 4, 2009; doi:10.1152/jn.91081.2008. Electric stimulation of the retina reliably elicits light percepts in patients blinded by outer retinal diseases. However, individual percepts are highly variable and do not readily assemble into more complex visual images. As a result, the quality of visual information conveyed to patients has been quite limited. To develop more effective stimulation methods that will lead to improved psychophysical outcomes, we are studying how retinal neurons respond to electric stimulation. The situation in the retina is analogous to other neural prosthetic applications in which a better understanding of the underlying neural response may lead to improved clinical outcomes. Here, we determined which element in retinal ganglion cells has the lowest threshold for initiating action potentials. Previous studies suggest multiple possibilities, although all were within the soma/proximal axon region. To determine the actual site, we measured thresholds in a dense two-dimensional grid around the soma/proximal axon region of rabbit ganglion cells in the flat mount preparation. In directionally selective (DS) ganglion cells, the lowest thresholds were found along a small section of the axon, about 40 mu m from the soma. Immunochemical staining revealed a dense band of voltage-gated sodium channels centered at the same location, suggesting that thresholds are lowest when the stimulating electrode is closest to the sodium-channel band. The size and location of the low-threshold region was consistent within DS cells, but varied for other ganglion cell types. Analogously, the length and location of sodium channel bands also varied by cell type. Consistent with the differences in band properties, we found that the absolute (lowest) thresholds were also different for different cell types. Taken together, our results suggest that the sodium-channel band is the site that is most responsive to electric stimulation and that differences in the bands underlie the threshold differences we observed.