Department of Electrical and Computer Engineering, University of Southern California, Los Angeles, CA, United States of America.
Institute for Technology and Medical Systems (ITEMS), Keck School of Medicine, University of Southern California, Los Angeles, CA, United States of America.
J Neural Eng. 2021 Dec 15;18(6). doi: 10.1088/1741-2552/ac3dd8.
. Retinal implants have been developed to electrically stimulate healthy retinal neurons in the progressively degenerated retina. Several stimulation approaches have been proposed to improve the visual percept induced in patients with retinal prostheses. We introduce a computational model capable of simulating the effects of electrical stimulation on retinal neurons. Leveraging this computational platform, we delve into the underlying mechanisms influencing the sensitivity of retinal neurons' response to various stimulus waveforms.. We implemented a model of spiking bipolar cells (BCs) in the magnocellular pathway of the primate retina, diffuse BC subtypes (DB4), and utilized our multiscale admittance method (AM)-NEURON computational platform to characterize the response of BCs to epiretinal electrical stimulation with monophasic, symmetric, and asymmetric biphasic pulses.. Our investigations yielded four notable results: (a) the latency of BCs increases as stimulation pulse duration lengthens; conversely, this latency decreases as the current amplitude increases. (b) Stimulation with a long anodic-first symmetric biphasic pulse (duration > 8 ms) results in a significant decrease in spiking threshold compared to stimulation with similar cathodic-first pulses (from 98.2 to 57.5A). (c) The hyperpolarization-activated cyclic nucleotide-gated channel was a prominent contributor to the reduced threshold of BCs in response to long anodic-first stimulus pulses. (d) Finally, extending the study to asymmetric waveforms, our results predict a lower BCs threshold using asymmetric long anodic-first pulses compared to that of asymmetric short cathodic-first stimulation.. This study predicts the effects of several stimulation parameters on spiking BCs response to electrical stimulation. Of importance, our findings shed light on mechanisms underlying the experimental observations from the literature, thus highlighting the capability of the methodology to predict and guide the development of electrical stimulation protocols to generate a desired biological response, thereby constituting an ideal testbed for the development of electroceutical devices.
视网膜植入物已被开发用于电刺激逐渐退化的视网膜中的健康视网膜神经元。已经提出了几种刺激方法来改善视网膜假体患者的视觉感知。我们引入了一种能够模拟电刺激对视网膜神经元影响的计算模型。利用这个计算平台，我们深入研究了影响视网膜神经元对各种刺激波形的响应灵敏度的潜在机制。我们在灵长类动物视网膜大细胞通路中实现了一个尖峰双极细胞（BC）模型，扩散 BC 亚型（DB4），并利用我们的多尺度导纳方法（AM）-NEURON 计算平台来表征 BC 对视网膜电刺激的反应，使用单相、对称和非对称双相脉冲。我们的研究得出了四个显著结果：（a）BC 的潜伏期随着刺激脉冲持续时间的延长而增加；相反，随着电流幅度的增加，潜伏期减小。（b）与类似的阴极首先脉冲（从 98.2 到 57.5A）相比，用长阳极首先对称双相脉冲（持续时间>8ms）刺激会导致尖峰阈值显著降低。（c）超极化激活环核苷酸门控通道是导致 BC 对长阳极首先刺激脉冲响应阈值降低的主要因素。（d）最后，将研究扩展到非对称波形，我们的结果预测使用非对称长阳极首先脉冲比使用非对称短阴极首先刺激时，BC 的阈值更低。这项研究预测了几种刺激参数对电刺激时尖峰 BC 响应的影响。重要的是，我们的发现阐明了文献中实验观察结果的潜在机制，从而突出了该方法预测和指导电刺激方案开发以产生所需生物学反应的能力，因此构成了电治疗设备开发的理想试验台。
