Neural activity of functionally different retinal ganglion cells can be robustly modulated by high-rate electrical pulse trains

Objective. This study focused on characterising the response of four major functionally-different retinal ganglion cells (RGCs) to a high frequency stimulus (HFS) paradigm. Approach. We used in vitro patch clamp experiments to assess the viability of evoking a differential response between different RGC types - OFF-Sustained, OFF-Transient, ON-Sustained and ON-Transient - under a wide range of HFS and stimulation amplitude combinations. Main results. Of the four types, we found that the OFF-Sustained, OFF-Transient and ON-Transient RGCs could be differentially activated at various frequency and amplitude combinations, in particular, OFF-Sustained cells can be differentially targeted between 20-100 µA at all frequencies, OFF-Transient cells between 150-240 µA at 1 kHz and ON-Transient between 180-240 µA and 4-6 kHz. We further found that this differential activation held true when the stimulus duration was reduced from 300 ms to 50 ms. Finally, we found that the cell spiking response was not primarily dependent on total charge contained in the pulse train or current amplitude alone, but a combination of amplitude and frequency. Significance. These results indicate that HFS may be a promising method to target functionally-distinct neural pathways in the retina in an effort to improve the vision quality with retinal prostheses.