Electric stimulus duration alters network-mediated responses depending on retinal ganglion cell type

Maesoon Im,Shelley I Fried,Paul Werginz

doi:10.1088/1741-2552/aaadc1

Abstract

Objective. To improve the quality of artificial vision that arises from retinal prostheses, it is important to bring electrically-elicited neural activity more in line with the physiological signaling patterns that arise normally in the healthy retina. Our previous study reported that indirect activation produces a closer match to physiological responses in ON retinal ganglion cells (RGCs) than in OFF cells (Im and Fried 2015 J. Physiol. 593 3677–96). This suggests that a preferential activation of ON RGCs would shape the overall retinal response closer to natural signaling. Recently, we found that changes to the rate at which stimulation was delivered could bias responses towards a stronger ON component (Im and Fried 2016a J. Neural Eng. 13 025002), raising the possibility that changes to other stimulus parameters can similarly bias towards stronger ON responses. Here, we explore the effects of changing stimulus duration on the responses in ON and OFF types of brisk transient (BT) and brisk sustained (BS) RGCs. Approach. We used cell-attached patch clamp to record RGC spiking in the isolated rabbit retina. Targeted RGCs were first classified as ON or OFF type by their light responses, and further sub-classified as BT or BS types by their responses to both light and electric stimuli. Spiking in targeted RGCs was recorded in response to electric pulses with durations varying from 5 to100 ms. Stimulus amplitude was adjusted at each duration to hold total charge constant for all experiments. Main results. We found that varying stimulus durations modulated responses differentially for ON versus OFF cells: in ON cells, spike counts decreased significantly with increasing stimulus duration while in OFF cells the changes were more modest. The maximum ratio of ON versus OFF responses occurred at a duration of ~10 ms. The difference in response strength for BT versus BS cells was much larger in ON cells than in OFF cells. Significance. The stimulation rates preferred by subjects during clinical trials are similar to the rates that maximize the ON/OFF response ratio in in vitro testing (Im and Fried 2016a J. Neural Eng. 13 025002). Here, we determine the stimulus duration that produces the strongest bias towards ON responses and speculate that it will further enhance clinical effectiveness.

Highlights

Outer retinal degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) can cause profound dysfunction of retinal neurons, and lead to blindness
Targeted cells were classified into known types using a combination of light and electrical responses; only cells identified as ON or OFF versions of brisk transient (BT) and brisk sustained (BS) cells were targeted for subsequent investigation
The total spike counts in ON BT cells were much larger than those of OFF BT cells across a wide range of stimulus durations (Fig. 3a)

Summary

Introduction

Outer retinal degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) can cause profound dysfunction of retinal neurons, and lead to blindness. Implants with a large number of densely packed electrodes provide only a modest improvement in visual acuity or in the ability to recognize objects, as compared to devices that have fewer and more widelyspaced electrodes (Zrenner et al 2011; Stingl et al 2013; da Cruz et al 2013). This suggests that further improvements in the quality of elicited vision will require advances beyond mere increases to the quantity and/or density of independent stimulating channels

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