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Perry Twyford, Shelley Fried; High-Frequency Electrical Stimulation Produces Differential Responses in ON and OFF Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):351.
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© ARVO (1962-2015); The Authors (2016-present)
The performance of existing retinal prosthetics is likely limited by the inability of electrical stimuli to selectively activate particular retinal ganglion cell (RGC) types. As different RGC types each code for different aspects of the visual scene, they often have dissimilar or diametric activity patterns, and activating them simultaneously via prosthetic stimulation results in non-physiological input to the brain. Discovery of a stimulus pattern capable of producing differential patterns of activity in different RGC types has the potential to increase the clinical outcome of current generation retinal prosthetics.
Cell-attached patch clamping was used to record spikes from ganglion cells in the isolated rabbit retina. Ganglion cells were classified as ON or OFF Brisk Transient (BT) cells by their response to stationary light flashes. After cell type classification, electrical stimulation was applied via an external cone electrode (10 kΩ, Platinum-Iridium) centered over the axon initial segment. Stimulation consisted of a biphasic stimulus applied at 2000 pulses per second. This waveform was then convolved with an envelope which transiently modulated the stimulus amplitude. Elicited responses were recorded for all cells (ON-BT, n = 7; OFF-BT, n = 7).
For one stimulus envelope, ON-BT cells exhibited an increase in activity while OFF-BT cells showed a decrease in activity. For a different stimulus envelope, OFF-BT cells exhibited an increase in activity while ON-BT cells showed a decrease in activity. Thus we are able to more closely match electrical response patterns to physiological responses to light stimuli.
Our results demonstrate the ability of amplitude modulated high-frequency stimulation to produce differential activity patterns in different cell-types. This may allow prosthetic devices to more closely match physiological response patterns, thereby improving percept quality. Further testing is underway to determine stimulus parameters that maximize the differential responses between cell-types.
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