Selectivity of direct and network-mediated stimulation of the retinal ganglion cells with epi-, sub- and intraretinal electrodes

Abstract

Objective Intra-retinal placement of stimulating electrodes can provide close and stable proximity to target neurons. We assessed improvement in stimulation thresholds and selectivity of the direct and network-mediated retinal stimulation with intraretinal electrodes, compared to epiretinal and subretinal placements. Approach Stimulation thresholds of the retinal ganglion cells (RGCs) in wild-type rat retina were measured using patch-clamp technique. Direct and network-mediated responses were discriminated using various synaptic blockers. Main results Three types of RGC responses were identified: short latency (SL, τ<5ms) originating in RGCs, medium latency (ML, 3<τ<70ms) originating in the inner nuclear layer and long latency (LL, τ>40ms) originating in photoreceptors. Cathodic epiretinal stimulation exhibited the lowest threshold for direct RGC response and the highest direct selectivity (network/direct thresholds ratio), exceeding a factor of 3 with pulse durations below 0.5ms. For network-mediated stimulation, the lowest threshold was obtained with anodic pulses in OPL position, and its network selectivity (direct/network thresholds ratio) increased with pulse duration, exceeding a factor of 4 at 10ms. Latency of all three types of responses decreased with increasing strength of the stimulus. Significance These results define optimal range of pulse durations, pulse polarities and electrode placement for the retinal prostheses aiming at direct or network-mediated stimulation of RGCs.

Stimulation of a Suprachoroidal Retinal Prosthesis Drives Cortical Responses in a Feline Model of Retinal Degeneration

“…Our previous studies acknowledged the possibility that photoreceptive responses to stimulation may have confounded analyses. 16,18 Based on recent data by Boinagrov et al 33 and our present data including the short response latencies and lack of any correlation between residual outer nuclear layer thickness and cortical thresholds, we can confirm that photoreceptors are not the primary target cell population with suprachoroidal stimulation.…”

“…2C). A 3-to 20-ms window was chosen in order to capture most of the retinal ganglion cell (short latency) and inner retinal-mediated (medium latency) activities as reported by Boinagrov et al, 33 while reducing the possibility that cortical feedback might confound spike analysis, and maintaining a consistent analysis window with previous studies. A preliminary analysis of longer windows, up to 400 ms, did not reveal activity beyond 20 ms that had the capacity to significantly contribute to cortical threshold.…”

“…12 Although we believe our analysis window accounts for the majority of ganglion cell and inner retinal mediated activity, 33 a more thorough analysis of later window activity would be very useful to further tease out the contribution of various surviving or degenerated cell types in the retina. Given that the response latencies triggered by activation of different cell types have significant overlap, perhaps a study involving the application of retinal blockers in degenerated retina in a manner similar to Boinagrov et al 33 would be the logical next step to further examine retinal contributions independently.…”

Interactions of Prosthetic and Natural Vision in Animals With Local Retinal Degeneration

“…Indeed, anodic-first pulses elicit network-mediated responses of ganglion cells with thresholds three to four times lower than cathodic-first pulses. 14 Photovoltaic arrays consisted of 1-mm-diameter and 30-lm-thick structures (Fig. 1A) composed of 140-lm pixels, separated by 5-lm-wide trenches (Fig.…”

The Spatial Extent of Epiretinal Electrical Stimulation in the Healthy Mouse Retina

“…Likewise, a spontaneous rate, chosen to best characterize the baseline firing rate within the context of ongoing electrical stimulation, was calculated from the 1 s of recording time before each pulse and averaged across all samples. The response integration window of 10 to 100 was chosen to exclude spikes generated by either direct RGC stimulation which have a latency <10 ms [12, 16, 17] or spontaneous spikes which make a significant contribution at latencies >100 ms [18, 19]. …”