Inferring light responses of primate retinal ganglion cells using intrinsic electrical signatures.

Objective. Retinal implants are designed to stimulate retinal ganglion cells (RGCs) in a way that restores sight to individuals blinded by photoreceptor degeneration. Reproducing high-acuity vision with these devices will likely require inferring the natural light responses of diverse RGC types in the implanted retina, without being able to measure them directly. Here we demonstrate an inference approach that exploits intrinsic electrophysiological features of primate RGCs.Approach.First, ON-parasol and OFF-parasol RGC types were identified using their intrinsic electrical features in large-scale multi-electrode recordings from macaque retina. Then, the electrically inferred somatic location, inferred cell type, and average linear-nonlinear-Poisson model parameters of each cell type were used to infer a light response model for each cell. The accuracy of the cell type classification and of reproducing measured light responses with the model were evaluated.Main results.A cell-type classifier trained on 246 large-scale multi-electrode recordings from 148 retinas achieved 95% mean accuracy on 29 test retinas. In five retinas tested, the inferred models achieved an average correlation with measured firing rates of 0.49 for white noise visual stimuli and 0.50 for natural scenes stimuli, compared to 0.65 and 0.58 respectively for models fitted to recorded light responses (an upper bound). Linear decoding of natural images from predicted RGC activity in one retina showed a mean correlation of 0.55 between decoded and true images, compared to an upper bound of 0.81 using models fitted to light response data.Significance.These results suggest that inference of RGC light response properties from intrinsic features of their electrical activity may be a useful approach for high-fidelity sight restoration. The overall strategy of first inferring cell type from electrical features and then exploiting cell type to help infer natural cell function may also prove broadly useful to neural interfaces.

Focal electrical stimulation of human retinal ganglion cells for vision restoration.

Objective. Vision restoration with retinal implants is limited by indiscriminate simultaneous activation of many cells and cell types, which is incompatible with reproducing the neural code of the retina. Recent work has shown that primate retinal ganglion cells (RGCs), which transmit visual information to the brain, can be directly electrically activated with single-cell, single-spike, cell-type precision - however, this possibility has never been tested in the human retina. In this study we aim to characterize, for the first time, direct in situ extracellular electrical stimulation of individual human RGCs.Approach. Extracellular electrical stimulation of individual human RGCs was conducted in three human retinas ex vivo using a custom large-scale, multi-electrode array capable of simultaneous recording and stimulation. Measured activation properties were compared directly to extensive results from macaque.Main results. Precise activation was in many cases possible without activating overlying axon bundles, at low stimulation current levels similar to those used in macaque. The major RGC types could be identified and targeted based on their distinctive electrical signatures. The measured electrical activation properties of RGCs, combined with a dynamic stimulation algorithm, was sufficient to produce an evoked visual signal that was nearly optimal given the constraints of the interface.Significance. These results suggest the possibility of high-fidelity vision restoration in humans using bi-directional epiretinal implants.