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D. K. Freeman, D. K. Eddington, J. F. Rizzo, S. I. Fried; Individual Classes of Retinal Neurons Can Be Selectively Activated by Modulating the Frequency of Electric Stimulation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5181.
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© ARVO (1962-2015); The Authors (2016-present)
The healthy retina is commonly used as a model for retinal prostheses research, but such prostheses are used clinically only in degenerate retinas, whose photoreceptors are largely eliminated. We sought to determine the appropriateness of the healthy retina for retinal prostheses research by measuring the level of involvement of photoreceptors in the response to electric stimulation of the inner retina.
Cell-attached patch clamping was used to record spikes from rabbit retinal ganglion cells in the isolated rabbit retina. Electric stimulation was delivered using a 10kOhm metal electrode placed 25µm above the ganglion cell soma. Spikes were recorded in response to sinusoidal stimuli of 5 -100Hz.
Photoreceptors were found to be highly sensitive to sinusoidal stimulation of 5Hz, which was evident by the difference in spiking responses seen between ON and OFF ganglion cells. OFF cells elicited spikes during the cathodal phase while ON cells elicited spikes during the anodal phase. This is consistent with photoreceptors being activated by cathodal stimulation, which for the ON pathway results in a suppression of spiking due to the sign-inverting synapse in the ON pathway but not the OFF pathway. This was confirmed by applying the mGluR blocker APB, which eliminated the response to 5Hz in ON cells. Increasing stimulus frequency past 10Hz caused the responses occur at identical phases for ON and OFF cells, suggesting a neuronal target that is downstream of the photoreceptors.
Photoreceptors are recruited during electric stimulation of the inner retina, and their level of involvement depends on the stimulus waveform used, where stimuli with energy at low frequencies (e.g. long duration pulses) will most effectively activate photoreceptors.
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