Efficient Inference of Sensitivity to Electrical Stimulation from Intrinsic Electrical Properties of Primate Retinal Ganglion Cells

Madugula, S. S.; Grosberg, L. E.; Shah, N. P.; Kling, A.; Goglietino, A. R.; Hottowy, P.; Sher, A.; Litke, A. M.; Chichilnisky, E. J.

doi:10.1101/2021.10.22.465478

bioRxiv · 10.1101/2021.10.22.465478

Efficient Inference of Sensitivity to Electrical Stimulation from Intrinsic Electrical Properties of Primate Retinal Ganglion Cells

Madugula, S. S.·Grosberg, L. E.·Shah, N. P.·Kling, A.·Goglietino, A. R.·Hottowy, P.·Sher, A.·Litke, A. M.·Chichilnisky, E. J.

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Abstract

High-fidelity electronic implants can in principle restore the function of neural circuits by precisely activating neurons via extracellular stimulation. However, direct characterization of the individual electrical responses of a large population of target neurons, in order to precisely control their activity, is often difficult or impossible. A potential solution is to leverage biophysical principles to infer sensitivity to electrical stimulation from features of spontaneous electrical activity, which can be recorded relatively easily. Here, this approach is developed and its potential value for vision restoration is tested quantitatively using large-scale high-density stimulation and recording from primate retinal ganglion cells (RGCs) ex vivo. Electrodes recording larger spikes from a given cell exhibited lower stimulation thresholds, with distinct trends for somas and axons, across cell types, retinas, and eccentricities. Thresholds for somatic stimulation increased with distance from the axon initial segment. The dependence of spike probability on injected current was inversely related to threshold, and was substantially steeper for axonal than somatic compartments, which could be identified by recorded electrical signatures. Dendritic stimulation was largely ineffective for eliciting spikes. These findings were quantitatively reproduced with biophysical simulations, and confirmed in tests on human RGCs. The inference of stimulation sensitivity from recorded electrical features was tested in simulated visual reconstruction, and revealed that the approach could significantly improve the function of future high-fidelity retinal implants.

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Madugula, S. S., Grosberg, L. E., Shah, N. P., Kling, A., Goglietino, A. R., Hottowy, P., Sher, A., Litke, A. M., Chichilnisky, E. J.. 2021-10-27. Efficient Inference of Sensitivity to Electrical Stimulation from Intrinsic Electrical Properties of Primate Retinal Ganglion Cells. https://doi.org/10.1101/2021.10.22.465478

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