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.
Highlights
Extracellular electrical stimulation is extensively used in electroneural interfaces for the central and peripheral nervous systems (Gybels, 1981; Deep-Brain Stimulation for Parkinson’s Disease Study Group et al, 2001; Kilgore and Bhadra, 2004; Guenther et al, 2012)
Considerable research into high-frequency electrical stimulation (HFS) is underway to understand the extent to which neuronal activity can be quantitatively controlled with greater spatiotemporal precision, in order to improve the performance of neuroprostheses
We began by stimulating the model retinal ganglion cell (RGC) with conventional 2-kHz extracellular biphasic pulse trains
Summary
Extracellular electrical stimulation is extensively used in electroneural interfaces for the central and peripheral nervous systems (Gybels, 1981; Deep-Brain Stimulation for Parkinson’s Disease Study Group et al, 2001; Kilgore and Bhadra, 2004; Guenther et al, 2012). Retinal prosthesis aims to restore functional visual percepts to those suffering from retinal degenerative diseases, by electrically stimulating the surviving neural tissue of the retina (Rizzo and Wyatt, 1997; Palanker et al, 2005; Weiland et al, 2005). In such cases, the aim is to elicit visual percepts by activating the remaining retinal neuronal populations in a controlled spatiotemporal pattern. Recent clinical studies have begun to assess how HFS might affect the efficacy of neural implants for the cochlear (up to 2.4 kHz) (McKay et al, 2013), the retina (up to 3.33 kHz) (Horsager et al, 2009), and the spinal cord (up to 10 kHz) (Tiede et al, 2013; Van Buyten et al, 2013)
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