Subretinal electrical stimulation reveals intact network activity in the blind mouse retina.
Subretinal electrical stimulation reveals intact network activity in the blind mouse retina.
复制标题
视网膜下电刺激揭示了失明小鼠视网膜中完整的网络活动。
作者：
H. Stutzki;F. Helmhold;Max Eickenscheidt;G. Zeck
视网膜变性（rd）导致进行性感光细胞死亡，导致视力丧失。通过神经假体植入物刺激视网膜内神经元是临床上批准的视力恢复策略之一，为盲人提供基本的视觉感知。然而，很少有人知道退化的视网膜回路和由此产生的异常活动过度在多大程度上可以阻止生理电活动的刺激。因此，我们电刺激离体视网膜野生型（野生型; C57 BL/6 J）和盲（rd 10和rd 1）小鼠使用植入式视网膜下微芯片，同时记录和分析视网膜神经节细胞（RGC）输出与灵活的微电极阵列。我们发现，视网膜下阳极刺激的rd 10视网膜和野生型视网膜诱发类似的时空RGC尖峰模式。在这两个视网膜，电刺激ON和OFF RGC反应的一小部分被检测到。视网膜网络对电刺激的空间选择性揭示了一个完整的底层网络，在两个视网膜中的中值感受场中心为350 μm。通过大电极场的刺激激活拮抗性环绕。然而，在rd 10和更高的百分比，在rd 1视网膜，节奏和空间上不受限制的RGC模式引起的阳极或阴极电刺激。我们的研究结果表明，在光感受器退化的视网膜中，幸存的视网膜回路是以允许刺激时间多样性和空间受限的RGC活动的方式保存的。未来的视力恢复策略可以建立在这些结果的基础上，但需要避免在某些视网膜回路中引起容易诱导的节律活动。
Retinal degeneration (rd) leads to progressive photoreceptor cell death, resulting in vision loss. Stimulation of the inner-retinal neurons by neuroprosthetic implants is one of the clinically approved vision-restoration strategies, providing basic visual percepts to blind patients. However, little is understood as to what degree the degenerating retinal circuitry and the resulting aberrant hyperactivity may prevent the stimulation of physiological electrical activity. Therefore, we electrically stimulated ex vivo retinas from wild-type (wt; C57BL/6J) and blind (rd10 and rd1) mice using an implantable subretinal microchip and simultaneously recorded and analyzed the retinal ganglion cell (RGC) output with a flexible microelectrode array. We found that subretinal anodal stimulation of the rd10 retina and wt retina evoked similar spatiotemporal RGC-spiking patterns. In both retinas, electrically stimulated ON and a small percentage of OFF RGC responses were detected. The spatial selectivity of the retinal network to electrical stimuli reveals an intact underlying network with a median receptive-field center of 350 μm in both retinas. An antagonistic surround is activated by stimulation with large electrode fields. However, in rd10 and to a higher percentage, in rd1 retinas, rhythmic and spatially unconfined RGC patterns were evoked by anodal or by cathodal electrical stimuli. Our findings demonstrate that the surviving retinal circuitry in photoreceptor-degenerated retinas is preserved in a way allowing for the stimulation of temporally diverse and spatially confined RGC activity. Future vision restoration strategies can build on these results but need to avoid evoking the easily inducible rhythmic activity in some retinal circuits.
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影响因子：
--
作者：
Santos, A;Humayun, MS;Milam, AH
通讯作者：
Milam, AH
影响因子：
5.2
作者：
Santos-Ferreira, Tiago;Postel, Kai;Ader, Marius
通讯作者：
Ader, Marius
影响因子：
64.8
作者：
Baden T;Berens P;Franke K;Román Rosón M;Bethge M;Euler T
通讯作者：
Euler T
影响因子：
2.5
作者：
Stasheff, Steven F.
通讯作者：
Stasheff, Steven F.