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Daniel Llewellyn Rathbun, Archana Jalligampala, Eberhart Zrenner; Characterization of indirect ganglion cell responses to electrical stimulation in the mouse retina.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):775.
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© ARVO (1962-2015); The Authors (2016-present)
The most successful approach for vision restoration following retinal degeneration-induced blindness so far has been electrical stimulation of the retina via neuroprosthetic devices. Such stimulation restores visual perception by creating a pattern of action potentials (spikes) in the optic nerve that approximates that found during healthy vision. While some prostheses seek to control the spike pattern through direct stimulation of retinal ganglion cells (RGCs), we target the underlying retinal network. This indirect stimulation of RGCs via electrical stimulation of second order neurons (e.g. bipolar cells), however, results in complex spike patterns that remain poorly understood. Here we present our efforts to demystify these spike patterns.
Spiking responses of adult mouse RGCs were recorded in vitro with a planar multielectrode array. Monophasic voltage pulses with 114 unique voltage-duration combinations (+ 2.5 V to -2.5 V, 0.06 to 5 ms, 5 repetitions each, interpulse interval ≥5 s) were delivered from the ganglion cell side of the retina (epiretinal configuration). A full-field white flash stimulus (2 s ON, 2 s OFF) was cycled 20x without pause in each of 6 stimulus blocks, interleaved with the electrical stimulation. To quantify the preference of RGCs for either positive or negative voltage pulses, a voltage polarity index was created. To quantify how much RGC responses decreased above the voltage that produced a maximal response, a suppression index was created.
The polarity index revealed that although all cells responded to negative voltages, only a subset of cells also responded to positive voltages. The suppression index revealed that the majority of RGCs did not have significant response suppression above the voltage required for a peak response. Simple visual response characteristics (amplitude, latency, and duration of ON and OFF responses) had only weak correspondence to the polarity index and suppression index.
Electrical response patterns resulting from indirect RGC stimulation are diverse. Although we were unable to demonstrate strong correlations between the electrical and visual response properties examined here, we continue to search for appropriate methods to distinguish the ~20 distinct RGC types that have been identified using morphological analysis.
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