Sekhar S, Jalligampala A, Zrenner E, Rathbun D L
Institute for Ophthalmic Research, Eberhard Karls University, D-72076 Tübingen, Germany. Werner Reichardt Centre for Integrative Neuroscience (CIN), D-72076 Tübingen, Germany. Graduate Training Center of Neuroscience/International Max Planck Research School, D-72074 Tübingen, Germany. Bernstein Center for Computational Neuroscience Tübingen, D-72076 Tübingen, Germany.
J Neural Eng. 2016 Aug;13(4):046004. doi: 10.1088/1741-2560/13/4/046004. Epub 2016 May 17.
The field of retinal prosthetics has made major progress over the last decade, restoring visual percepts to people suffering from retinitis pigmentosa. The stimulation pulses used by present implants are suprathreshold, meaning individual pulses are designed to activate the retina. In this paper we explore subthreshold pulse sequences as an alternate stimulation paradigm. Subthreshold pulses have the potential to address important open problems such as fading of visual percepts when patients are stimulated at moderate pulse repetition rates and the difficulty in preferentially stimulating different retinal pathways.
As a first step in addressing these issues we used Gaussian white noise electrical stimulation combined with spike-triggered averaging to interrogate whether a subthreshold sequence of pulses can be used to activate the mouse retina.
We demonstrate that the retinal network can integrate multiple subthreshold electrical stimuli under an experimental paradigm immediately relevant to retinal prostheses. Furthermore, these characteristic stimulus sequences varied in their shape and integration window length across the population of retinal ganglion cells.
Because the subthreshold sequences activate the retina at stimulation rates that would typically induce strong fading (25 Hz), such retinal 'tickling' has the potential to minimize the fading problem. Furthermore, the diversity found across the cell population in characteristic pulse sequences suggests that these sequences could be used to selectively address the different retinal pathways (e.g. ON versus OFF). Both of these outcomes may significantly improve visual perception in retinal implant patients.
在过去十年中,视网膜假体领域取得了重大进展,为患有色素性视网膜炎的患者恢复了视觉感知。目前植入物使用的刺激脉冲是阈上的,这意味着单个脉冲旨在激活视网膜。在本文中,我们探索阈下脉冲序列作为一种替代刺激模式。阈下脉冲有可能解决一些重要的未解决问题,例如当以中等脉冲重复率刺激患者时视觉感知的消退,以及优先刺激不同视网膜通路的困难。
作为解决这些问题的第一步,我们使用高斯白噪声电刺激结合触发尖峰平均法来探究阈下脉冲序列是否可用于激活小鼠视网膜。
我们证明,在与视网膜假体直接相关的实验范式下,视网膜网络可以整合多个阈下电刺激。此外,这些特征性刺激序列在视网膜神经节细胞群体中的形状和整合窗口长度各不相同。
由于阈下序列以通常会导致强烈消退的刺激率(25赫兹)激活视网膜,这种视网膜“挠痒”有可能将消退问题降至最低。此外,在细胞群体中发现的特征脉冲序列的多样性表明,这些序列可用于选择性地作用于不同的视网膜通路(例如开与关)。这两个结果都可能显著改善视网膜植入患者的视觉感知。