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S. I. Fried, A. C. Lasker, D. K. Eddington, J. F. Rizzo; Two Different Parts of the Ganglion Cell Axon Are Activated by Epi-Retinal Electrical Stimulation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3034.
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© ARVO (1962-2015); The Authors (2016-present)
In blind patients, electric stimulation of the retina generates visual percepts called phosphenes. In order to better understand the neural response that underlies these percepts, we determined which part(s) of the retinal ganglion cell (axon, soma, etc.) is activated by stimulation. Our results provide fundamental information for the design of retinal prostheses for the blind.
We measured the ganglion cell response to electric stimulation in the flat-mount rabbit retina. Electric stimulation was delivered using a small-tipped Pt-Ir electrode with short duration (200 µs) cathodic pulses. Threshold levels for spike initiation were measured as a function of the stimulating electrode position as it was moved in 10 µm steps along the retinal surface. Fluorescent imaging and immunochemistry were used to correlate electrode position to specific anatomical features of the stimulated cells.
Two regions of low threshold were discovered. The position of the first, which was on the axon close to where it emerged from the soma, was somewhat variable but always corresponded to a small region that contained a high-density of sodium channels - presumably the initial segment. The second region of low threshold was also on the axon but at distances >~200 µm from the soma. The exact position was highly variable in this region and not correlated with a high density of sodium channels; rather this region was found to be associated with a migration of the axon toward the inner surface of the retina (i.e. closer to the stimulating electrode). Threshold levels were comparable in the two regions.
Our results indicate that electric stimulation targets two different regions of ganglion cells - one at the initial segment (near the soma) and the other at the axon but only for distances >~200 µm from the soma. This suggests that stimulation can activate local ganglion cells (i.e. those whose initial segments are close to the stimulating electrode) as well as distal ganglion cells (i.e. those whose axons pass close to the stimulating electrode). Activation of distal ganglion cells is not desirable as it presumably would create larger, less well-defined percepts. Since ‘focal’ percepts have been reported in many clinical trials, it is possible that ganglion cells were not being directly excited; instead neurons presynaptic to ganglion cells (i.e. bipolar cells) were activated.
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