Encoding visual information in retinal ganglion cells with prosthetic stimulation

Abstract

Retinal prostheses aim to restore functional vision to those blinded by outer retinal diseases using electric stimulation of surviving retinal neurons. The ability to replicate the spatiotemporal pattern of ganglion cell spike trains present under normal viewing conditions is presumably an important factor for restoring high-quality vision. In order to replicate such activity with a retinal prosthesis, it is important to consider both how visual information is encoded in ganglion cell spike trains, and how retinal neurons respond to electric stimulation. The goal of the current review is to bring together these two concepts in order to guide the development of more effective stimulation strategies. We review the experiments to date that have studied how retinal neurons respond to electric stimulation and discuss these findings in the context of known retinal signaling strategies. The results from such in vitro studies reveal the advantages and disadvantages of activating the ganglion cell directly with the electric stimulus (direct activation) as compared to activation of neurons that are presynaptic to the ganglion cell (indirect activation). While direct activation allows high temporal but low spatial resolution, indirect activation yields improved spatial resolution but poor temporal resolution. Finally, we use knowledge gained from in vitro experiments to infer the patterns of elicited activity in ongoing human trials, providing insights into some of the factors limiting the quality of prosthetic vision.

A Treatise of the Physical Aspects of Phosphenes and Single-Cell Selectivity in Retinal Stimulation

“…Experimental findings by Jepson [73] indicated similar thresholds for electrical stimulation of the five numerically dominant retinal ganglion cell types previously mentioned. These findings indicate that ON and OFF type cells fire temporally in phase [74]. ON and OFF type cells can be stimulated with arrays of electrodes with small diameter at comparable threshold levels [71].…”

“…The brightness or darkness of the elicited phosphene may be involved as to whether the ON or OFF pathways are being stimulated. Freeman et al, [74] suggested the possibility that the OFF pathway is outweighed by the signal from the ON pathway when both are activated identically by electric stimulation. Another possibility is that a bright phosphene results from preferential activation of ON versus OFF type ganglion cells.…”

“…This is because ON and OFF type cells are spatially intermixed [78] and the bright response of ON type cells overshadows the response of OFF cells and their activation is more preferred [74]. While the stimulus is delivered to the cells, the activation area can indicate the stimulation of RGCs regardless of the type and class because they have similar activation thresholds [71][72][73].…”

Emerging Gene Therapies for Retinal Degenerations

“…An exciting possibility building upon this strategy is being developed by several groups (Nirenberg, 2010;Freeman et al, 2011). They are delivering ChR2 to retinal ganglion cells, also via AAV, but hope to make the signals from these transduced retinal ganglion cells more informative to the brain by using the normal coding mechanisms of retinal ganglion cells.…”

Flexible Polyimide Microelectrodes Array for Transcorneal Electrical Stimulation

“…We believe that this strategy supposes to stimulate with different stimulation parameters, as well as to evaluate the effect of a mixture of several stimulation waveforms. There are two ways in which ganglion cell spiking can be elicited: either through direct activation, where the electric stimulus acts directly on the ganglion cell, or through indirect activation, where presynaptic neurons are activated by the electric stimulus and this results in a modulation of synaptic input to the ganglion cell [13].…”