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Ethan D Cohen, Esra Neufeld, Hazael Montanaro, Maria I Iacono, Leonardo M Angelone, Wolfgang Kainz; Development of an alpha retinal ganglion cell model for epiretinal electrode stimulation.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3716.
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© ARVO (1962-2015); The Authors (2016-present)
Using whole-cell recording and an epiretinal stimulus electrode similar in size to clinical electrodes, we investigated how the action potential thresholds of OFF-alpha retinal ganglion cells varied with stimulus electrode distance from the cell body, to develop a NEURON computational model of the alpha ganglion cell.
Under anesthesia, the retina from rabbits was isolated and perfused in Ames Ringer. Large ganglion cells were selected for whole-cell recording using dim red or IR Nomarski illumination. A small hole was made in the inner limiting membrane to allow pipette access. The frequency vs. current firing properties of the ganglion cell were studied using 100pA current steps. Next, a thin insulated 100µm diameter Pt stimulus electrode was positioned at a 30 degree angle near the axon hillock/soma approximately 50µm above the retina. A series of 0.5msec ascending cathodic, followed by anodic current pulses (20msec apart) were used to examine how firing threshold varied laterally with soma proximity in 100µm steps. After recording, the morphology of the dye-filled ganglion cell was imaged and processed with anti-lucifer yellow antibodies for confocal microscopic reconstruction. The morphology of selected cells were entered into Neurolucida for segmentation, fitted with ion channels in NEURON, and imported into a novel electromagnetic-neuronal dynamics modeling program to simulate extracellular stimulation.
When current steps were injected into the alpha cell body, a large pipette current was needed to elicit action potential threshold averaging 500±170pA (n=5 cells; mean ± std. dev). Some spike adaptation to firing was observed. Using epiretinal stimulus electrodes, action potentials were only generated by cathodic current pulses. When the electrode was placed adjacent to the cell body at the axon hillock region, thresholds for activation averaged 10.8±11.3nC (n= 5 cells; mean ± std. dev.). The spatial threshold for extracellular stimulation of the ganglion cells by the Pt electrode was localized to a region ~100µm around the initial segment/axon hillock of the cell body.
Large thinly insulated epiretinal stimulus electrodes activate action potentials in alpha ganglion cells in a spatially localized manner near the initial segment/soma region of the retinal ganglion cell. Synaptic activity may alter spike threshold.
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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