Journal
IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
Volume 28, Issue 9, Pages 1921-1930Publisher
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
DOI: 10.1109/TNSRE.2020.3003345
Keywords
Retinal prosthesis; electrical stimulation; electrophysiology; retinal ganglion cell; variability
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Funding
- Korea Institute of Science and Technology (KIST) [2E30080, 2E30140]
- National Research Foundation of Korea (NRF) - Korean Government (MSIT) [2020R1C1C1006065]
- VA Boston Healthcare System [1I01RX001663]
- National Eye Institute [R01EY023651]
- National Institute of Neurological Disorders and Stroke [R01NS110575]
- National Research Foundation of Korea [2020R1C1C1006065, 2E30140] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Retinal prostheses use periodic repetition of electrical stimuli to form artificial vision. To enhance the reliability of evoked visual percepts, repeating stimuli need to evoke consistent spiking activity in individual retinal ganglion cells (RGCs). However, it is not well known whether outer retinal degeneration alters the consistency of RGC responses. Hence, here we systematically investigated the trial-to-trial variability in network-mediated responses as a function of the degeneration level. We patch-clamp recorded spikes in ON and OFF types of alpha RGCs from r d10 mice at four different postnatal days (P15, P19, P31, and P60), representing distinct stages of degeneration. To assess the consistency of responses, we analyzed variances in spike count and timing across repeats of the same stimulus delivered multiple times. We found the trial-to-trial variability of network-mediated responses increased considerably as the disease progressed. Compared to responses taken before degeneration onset, those of degenerate retinas showed up to similar to 70% higher variability (Fano Factor) in spike counts (p < 0.001) and similar to 95% lower correlation level in spike timing (p < 0.001). These results indicate consistency weakens significantly in electrically-evoked network-mediated responses and therefore raise concerns about the ability of microelectronic retinal implants to elicit consistent visual percepts at advanced stages of retinal degeneration.
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