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Archana Jalligampala, Eberhart Zrenner, Daniel Llewellyn Rathbun; Spatial aspects of electrical desensitization in mouse retina. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3722.
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© ARVO (1962-2015); The Authors (2016-present)
Repetitive electrical stimulation of the retina causes desensitization during which retinal network responses to further stimulation are reduced. This has been shown to be a potential neural correlate of visual percept fading often reported by human visual prosthesis subjects. Earlier studies have investigated the temporal aspects of desensitization however the lesser known spatial component is poorly understood. Here we further investigate the above in healthy mouse retinas
Retinal ganglion cell (RGC) spiking responses were recorded invitro from adult wt mouse retinas (c57BL/6,P56-100) using multi-electrode array(MEA).Cathodal-first, biphasic,rectangular current pulses with varying stimulus amplitude (0.5-10µA at 1ms) were delivered epiretinally to obtain RGC thresholds.On obtaining the average threshold(mean ± SD) a series of pulse pairs (at 2x threshold) with different interpulse intervals(10-600ms) and varied spatial separation(200-1000µm) between the two pulses were presented to study the spatiotemporal effects of desensitization on RGC responses.Additionally, a high-density MEA(60 electrodes, 40µm pitch, 10µmØ) were used for dense spatial sampling(40-200µm).To examine multiple stimulus pulse effect, trains of ten stimuli(2- 62.5Hz) were also applied.
We found that the pulse paradigms required for effective stimulation of the retinal network werein agreement with previously published studies (n=20). Additionally,the RGC responses exhibited paired-pulse depression with decreasing interpulse interval and decreased responses with increasing frequency (n=15)suggesting quick adaption of the RGC responses.No desensitization was observed at interpulse distances>800µm.With decreasing distances the response of the second pulse with respect to first(priming) pulse decreased significantly until 100µm (n=14). For distances<100µm the responses to the second pulse were indiscernible.
Desensitization follows a nonlinear interaction of time and distance.This nonlinearity may be caused by various mechanisms (receptor desensitization, inhibitory feedback) which could discern the spatial spread of desensitization into local and global component, thereby providing a better understanding of fading. The minimal interelectrode distance to avoid desensitizing interactions is 800µm.Therefore a strategy of interleaved activation of electrodes separated by at least 800µm is recommended to avoid desensitization effects.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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