Mediating Retinal Ganglion Cell Spike Rates Using High-Frequency Electrical Stimulation

Abstract

Recent retinal studies have directed more attention to sophisticated stimulation strategies based on high-frequency (>1.0 kHz) electrical stimulation (HFS). In these studies, each retinal ganglion cell (RGC) type demonstrated a characteristic stimulus-strength-dependent response to HFS, offering the intriguing possibility of focally targeting retinal neurons to provide useful visual information by retinal prosthetics. Ionic mechanisms are known to affect the responses of electrogenic cells during electrical stimulation. However, how these mechanisms affect RGC responses is not well understood at present, particularly when applying HFS. Here, we investigate this issue via an in silico model of the RGC. We calibrate and validate the model using an in vitro retinal preparation. An RGC model based on accurate biophysics and realistic representation of cell morphology, was used to investigate how RGCs respond to HFS. The model was able to closely replicate the stimulus-strength-dependent suppression of RGC action potentials observed experimentally. Our results suggest that spike inhibition during HFS is due to local membrane hyperpolarization caused by outward membrane currents near the stimulus electrode. In addition, the extent of HFS-induced inhibition can be largely altered by the intrinsic properties of the inward sodium current. Finally, stimulus-strength-dependent suppression can be modulated by a wide range of stimulation frequencies, under generalized electrode placement conditions. In vitro experiments verified the computational modeling data. This modeling and experimental approach can be extended to further our understanding on the effects of novel stimulus strategies by simulating RGC stimulus-response profiles over a wider range of stimulation frequencies and electrode locations than have previously been explored.

Scaling of the AIS and Somatodendritic Compartments in α S RGCs

“…The AIS size difference for ON vs. OFF RGCs could also explain earlier findings in which more complex patterns of electric stimulation were able to differentially activate the two populations (Cai et al, 2013; Twyford et al, 2014). While the mechanism underlying differential sensitivity of the two types has yet to be unequivocally identified (but see Kameneva et al, 2016; Guo et al, 2019), the sensitivity differences between ON and OFF cells persist in the presence of synaptic blockers, suggesting that the differences arise from features intrinsic to the two cell types, most likely within the AIS themselves. The improved understanding of the AIS anatomy found here may lead to a better understanding of the mechanism underlying preferential selectivity and may also help to identify stimulation paradigms that provide even higher levels of selectivity.…”

Intermittent KHz-frequency electrical stimulation selectively engages small unmyelinated vagal afferents

“…Given the reported contribution of voltage-gated sodium channels in KES-induced neural activities in the central and peripheral nervous systems [47][48][49][50] , we sought to determine whether sodium channels could be at least in part responsible for the obtained selectivity in this study.…”

Stimulation Strategies for Improving the Resolution of Retinal Prostheses

“…This indicates that, different from Meng et al (2018), the upper threshold phenomenon may also happen in the RGC axons by biphasic stimulation. The potential mechanisms for the upper threshold phenomenon have been discussed in detail by Guo et al (2019). According to their discussion, the sodium channel kinetics in RGCs may play the major role in the upper threshold phenomenon.…”