Grosberg Lauren E, Ganesan Karthik, Goetz Georges A, Madugula Sasidhar S, Bhaskhar Nandita, Fan Victoria, Li Peter, Hottowy Pawel, Dabrowski Wladyslaw, Sher Alexander, Litke Alan M, Mitra Subhasish, Chichilnisky E J
Department of Neurosurgery and Hansen Experimental Physics Laboratory, Stanford University, Stanford, California;
Departments of Electrical Engineering and Computer Science, Stanford University, Stanford, California.
J Neurophysiol. 2017 Sep 1;118(3):1457-1471. doi: 10.1152/jn.00750.2016. Epub 2017 May 31.
Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses. Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.
用于治疗失明的视网膜外假体激活轴突束,产生大的弧形视觉感知,限制了人工视觉的质量。因此,改善视网膜外假体的功能需要了解并避免轴突束激活。本研究介绍了一种基于轴突束电信号特征来检测其激活的方法,并使用该方法测试视网膜外刺激是否能在不激活附近轴突束的情况下直接诱发单个视网膜神经节细胞产生动作电位。使用定制的多电极系统(512个电极,直径10μm,间距60μm)对分离的灵长类动物视网膜进行联合电刺激和记录。轴突束信号通过其双向传播、速度以及作为刺激电流函数的振幅增加来识别。轴突束激活的阈值在不同电极和视网膜之间有所变化,且与在神经节细胞胞体附近激活它们的阈值处于同一范围。在周边视网膜中,45%能激活单个神经节细胞的电极(占所有电极的17%)在不激活轴突束的情况下做到了这一点。这使得在阵列上能选择性激活21%记录到的神经节细胞(占预期神经节细胞的7%)。在一次中央视网膜记录中,75%能激活单个神经节细胞的电极(占所有电极的16%)在不激活轴突束的情况下做到了这一点。在不激活轴突束的情况下选择性激活一部分视网膜神经节细胞的能力为未来的视网膜外假体提出了一种可能的新型架构。大规模多电极记录和刺激被用于测试在不激活轴突束的情况下视网膜神经节细胞能被电激活的选择性程度。开发了一种基于轴突独特电信号特征来识别轴突激活的新方法,并用于发现一部分神经节细胞能在单细胞、单动作电位分辨率下被激活,而在外周和中央视网膜中不产生轴突束活动。这些发现对先进视网膜假体的开发具有启示意义。