Multiple components of ganglion cell desensitization in response to prosthetic stimulation.

Multiple components of ganglion cell desensitization in response to prosthetic stimulation.
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DOI:
10.1088/1741-2560/8/1/016008
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发表时间:
2011-02
影响因子:
4
通讯作者:
Fried SI
Fried SI
中科院分区:
工程技术2区
文献类型:
--
作者:
Freeman DK;Fried SI

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视网膜假体旨在通过电刺激存活的神经元来恢复那些因视网膜外部疾病而失明的人的功能视力。以前的工作表明,重复刺激激活突触网络的刺激降低了视网膜神经元对进一步刺激的敏感性。这种脱敏可能会导致人类受试者报告的视觉知觉随着时间的推移而褪色。在这里,我们表明脱敏可能比以前认为的更复杂。我们记录了兔视网膜神经节细胞的棘波序列,发现在抑制性阻滞剂(士的宁和印防己毒素)存在的情况下,脱敏现象持续存在,这表明无长突细胞的抑制不仅仅是降低对电刺激的敏感性的唯一原因。在突触介导的反应的同时脱敏过程中,神经节细胞直接激活的阈值变化不大,表明脱敏可能发生在棘波发生器的上游。除了快速脱敏作用超过几百毫秒(τ=176.4±8.8ms)外,我们还报告了时间为数秒的缓慢作用脱敏(τ=14.0±1.1秒)。我们发现的这两个脱敏成分的时间过程类似于人类受试者的两个亮度衰退阶段。这表明,由于脱敏导致的神经节细胞放电的减少可能是假体刺激引起的视觉感觉随时间的消退的原因。
Retinal prostheses aim to restore functional vision to those blinded by outer retinal diseases using electric stimulation of surviving neurons. Previous work indicates that repetitive stimulation with stimuli that activate the synaptic network reduces the sensitivity of retinal neurons to further stimulation. Such desensitization may contribute to the fading of visual percepts over time reported by human subjects. Here, we show that desensitization may be more complex than previously considered. We recorded spike trains from rabbit retinal ganglion cells and found that desensitization persists in the presence of inhibitory blockers (strychnine and picrotoxin), indicating amacrine cell inhibition is not solely responsible for reducing sensitivity in response to electric stimulation. The threshold for direct activation of the ganglion cell changes little during the simultaneous desensitization of the synaptically mediated response, indicating that desensitization likely occurs upstream of the spike generator. In addition to the rapid desensitization acting over hundreds of milliseconds (τ = 176.4 ± 8.8ms), we report the presence of a slow acting desensitization with a time course of seconds (τ = 14.0 ± 1.1sec). The time course of the two components of desensitization that we found are similar to the two phases of brightness fading seen in human subjects. This suggests that the reduction in ganglion cell firing due to desensitization may be responsible for the fading of visual percepts over time in response to prosthetic stimulation.
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