Affiliation:
1. Neuroretinal Electrophysiology and Imaging, Institute for Ophthalmic Research, Eberhard-Karls-Universität Tübingen, 72076 Tübingen, Germany
Abstract
Background: The electrical stimulation (stim) of retinal neurons enables blind patients to experience limited artificial vision. A rapid response outage of the stimulated ganglion cells (GCs) allows for a low visual sensation rate. Hence, to elucidate the underlying mechanism, we investigated different stim parameters and the role of the neuromodulator calcium (Ca2+). Methods: Subretinal stim was applied on retinal explants (blind rd1 mouse) using multielectrode arrays (MEAs) or single metal electrodes, and the GC activity was recorded using Ca2+ imaging or MEA, respectively. Stim parameters, including voltage, phase polarity, and frequency, were investigated using specific blockers. Results: At lower stim frequencies (<5 Hz), GCs responded synaptically according to the stim pulses (stim: biphasic, cathodic-first, −1.6/+1.5 V). In contrast, higher stim frequencies (≥5 Hz) also activated GCs directly and induced a rapid GC spike response outage (<500 ms, MEA recordings), while in Ca2+ imaging at the same frequencies, increased intracellular Ca2+ levels were observed. Conclusions: Our study elucidated the mechanisms involved in stim-dependent GC spike response outage: sustained high-frequency stim-induced spike outage, accompanied by electrogenically clamped intracellular Ca2+ levels at elevated levels. These findings will guide future studies optimizing stim paradigms for electrical implant applications for interfacing neurons.
Funder
Hector Fellow Academy
Tistou and Charlotte Kerstan Foundation
Deutsche Forschungsgemeinschaft and the Open Access Publishing Fund of the University of Tübingen
Cited by
1 articles.
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