Electrical stimulation precisely reproduces naturalistic spiking activity in complete and intermixed neural populations in the primate retina

Phillips, A. J.; Lotlikar, A.; Kling, A.; Hays, M.; Vasireddy, P.; Hofflich, B.; Sharon, A.; Sommeling, M. A.; Brown, J.; Baum, C.; Nguyen, H.; Lim, Y.-L.; Hottowy, P.; Sher, A.; Litke, A. M.; Chichilnisky, E. J.

doi:10.64898/2026.05.04.721188

bioRxiv · 10.64898/2026.05.04.721188

Electrical stimulation precisely reproduces naturalistic spiking activity in complete and intermixed neural populations in the primate retina

Phillips, A. J.·Lotlikar, A.·Kling, A.·Hays, M.·Vasireddy, P.·Hofflich, B.·Sharon, A.·Sommeling, M. A.·Brown, J.·Baum, C.·Nguyen, H.·Lim, Y.-L.·Hottowy, P.·Sher, A.·Litke, A. M.·Chichilnisky, E. J.

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Abstract

Neurostimulation technologies have the potential to restore complex brain functions by evoking naturalistic patterns of neural activity. However, faithfully mimicking the brains natural neural code in diverse neuron types remains an unsolved challenge. Here we exploit focal electrical stimulation and recording to reproduce natural visual signals at cellular resolution in two intermixed and oppositely-tuned neural populations in the isolated macaque retina. We calibrated and delivered electrical stimulation sequences to precisely mimic recorded visually-evoked responses to natural images in complete populations of ~50 ON and OFF parasol cells uniformly sampling ~4{degrees} x 4{degrees} of visual angle. Distinct and opposing visually-evoked response patterns in the two intermixed populations were closely replicated spike-by-spike in 5 retinal preparations using electrical stimulation, reproducing spike trains with 51 {+/-} 17% lower variability than repeated presentations of the same visual stimulus. Focal electrical stimulation also replicated traveling waves of neural activity in response to visual motion, and highly structured artificial response patterns. These findings demonstrate for the first time that neurostimulation can match or exceed biological signaling fidelity in large, complete and intermixed neural populations.

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Phillips, A. J., Lotlikar, A., Kling, A., Hays, M., Vasireddy, P., Hofflich, B., Sharon, A., Sommeling, M. A., Brown, J., Baum, C., Nguyen, H., Lim, Y.-L., Hottowy, P., Sher, A., Litke, A. M., Chichilnisky, E. J.. 2026-05-07. Electrical stimulation precisely reproduces naturalistic spiking activity in complete and intermixed neural populations in the primate retina. https://doi.org/10.64898/2026.05.04.721188

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