Optimal waveform parameters for extracellular activation of RGCs

Abstract

Purpose: Retinal prostheses seek to restore visual perception in the blind through electrical stimulation of surviving retinal ganglion cells (RGCs). While increased stimulus amplitude often results in greater neural activity, the influence of other waveform parameters such as phase duration on efficacy is unclear. We wished to determine the waveform parameters most effective in activating RGCs using planar electrodes fabricated from nitrogen-doped diamond.

Methods: We made whole-cell patch-clamp recordings from 40 A2-type RGCs in retinal whole mount preparations from 26 Sprague-Dawley rats. Membrane potential recordings were amplified (NPI, BA-1S), sampled at 50kHz and stored in digital form. Cells were stimulated using a 200μm square diamond electrode positioned epiretinally over the soma and driven by current injection (Multichannel Systems, MCS-4004). Stimuli were delivered against a distant monopolar return electrode.

Results: Phase duration and polarity had the largest effect on activation thresholds - cells were most responsive to cathodic pulses of short phase duration. Waveform asymmetry and increases in interphase interval affected lower thresholds. Efficacy for 20Hz and 200Hz stimulation dropped to ~65% and ~30% of efficacy at 1Hz respectively by the 20th pulse. Interestingly, cell size was found to correlate with temporal frequency tuning characteristics. Smaller A2 cells were better capable of following frequencies greater than 50Hz.

Conclusions: These results suggest that a careful choice of electrical waveform parameters can significantly improve prosthesis efficacy.

Keywords: 508 electrophysiology: non-clinical • 688 retina