Relating spontaneous activity to electrical stimulation properties of primate retinal ganglion cells

项目摘要/摘要 最有希望的光感受器退化的治疗选择，这是导致失明的主要原因 在美国，视网膜假体是通过手术植入前部视网膜以获得 电进入视网膜神经节细胞(RGC)，绕过受损的光感受器细胞层。尽管 由于市场上有少数FDA批准的视网膜前假体，表面高密度的RGC 使得从电极传输电流变得足够精确，从而很难概括自然 神经节细胞活动的模式，因此对盲人患者有用的视觉感知。这是由于粗略 电刺激引起视网膜前表面细胞和轴突不必要的活动，特别是在视网膜前表面 中央视网膜，细胞密度最大。这项研究的目的是使用来自自然RGC的信息 记录在多电极阵列上的活动，以便指导精确的、空间定向的电刺激。 仔细应用在组织中传播的电场特性来校准刺激电流将 允许视网膜前植入物在盲人患者中产生有意义的视觉感知。 给定RGC活动在阵列上的记录签名与其​电像之间的关系 (EI)-它对单电极或多电极刺激的敏感性-其​电感受野-将是 下定决心。首先，将在外围灵长类动物的视网膜上进行实验，以收集RGC激活的数据 响应于从阵列上的~500个电极中的每个电极输送电流的特性。接下来，我们将 将该模型扩展到在中缝中心较小、密集分布的RGC上收集的实验数据 视网膜的区域。尽管密集的电极间距，阵列在其精确传输的能力方面是有限的 靶向刺激由电极之间的距离决定。这可以通过弱刺激来解决。 多个相邻电极同时作用，推动交叉口刺激电流强度 多个产生的电场超过目标RGC激活所需的阈值。我们将刺激 用两到七个相邻的六边形排列的电极的组合来收集RGC ERF 外周和中央视网膜。一种用于模拟神经元放电的级联线性-非线性模型，将 将EIS作为输入，以预测整个阵列中的ERF。全面了解EI与ERF之间的关系 视网膜将实现设计高保真所需的闭合循环、精确的空间定位刺激 视网膜前装置，并揭示在中枢神经系统其他地方适用的一般原理。

Project Summary / Abstract The most promising treatment option for photoreceptor degeneration, which is the leading cause of blindness in the United States, are retinal prostheses that are surgically implanted on the anterior retina in order to gain electrical access to the retinal ganglion cells (RGCs), bypassing the damaged photoreceptor cell layer. Despite there being a few FDA approved epiretinal prostheses on the market, the high density of RGCs at the surface of the retina makes it difficult to deliver current from electrodes with enough precision to recapitulate the natural patterns of ganglion cell activity, and thus useful visual perception for blind patients. This is due to coarse electrical stimulation that evokes unwanted activity in cells and axons at the epiretinal surface, especially in the central retina where cells are the densest. The goal of this research is to use information from the natural RGC activity recorded on the multi-electrode array in order to guide precise, spatially targeted electrical stimulation. Careful application of the properties of electric fields propagating in tissue to calibrate stimulation currents will allow epiretinal implants to produce meaningful visual perception in blind patients. The relationship between the recorded signature of a given RGC’s activity on the array—its ​Electrical Image (EI)—and its sensitivity to single or multi-electrode stimulation—its ​Electrical Receptive Field (ERF)—will be determined. First, experiments will be conducted in peripheral primate retina to collect data on RGC activation characteristics in response to delivering current from each of the ~500 electrodes on the array. Next, we will extend this model to experimental data collected on the smaller, densely-packed RGCs in the central Raphe region of the retina. Despite dense electrode spacing, arrays are limited in their ability to deliver precisely targeted stimulation by the distance between electrodes. This can be addressed by weakly stimulating with multiple neighboring electrodes at the time same, pushing the strength of stimulation current at the intersection of the multiple generated electric fields over the threshold required for target RGC activation. We will stimulate with combinations of two to seven neighboring hexagonally arranged electrodes to collect RGC ERFs in the peripheral and central retina. An cascading linear-nonlinear model, popular for modeling neuronal spiking, will be fit with EIs as input to predict ERFs across the array. A thorough understanding of the EI-ERF relation in the retina will enable the closed-loop, precise, spatially localized stimulation necessary for designing a high-fidelity epiretinal device, and uncover general principles applicable elsewhere in the central nervous system.