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N. J. Desai, D. K. Eddington, J. F. Rizzo, III, S. Fried; Differences in Sodium Channel Bands Underlie Different Responses to Electrical Stimulation in Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1634.
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Electric stimulation of the retina of blind patients generates visual percepts called phosphenes. Eliciting complex visual detail has proven difficult however and we are therefore studying how retinal neurons respond to electric stimulation as a step towards improving clinical outcomes. We have recently shown that a dense band of sodium channels (SOC) located in the proximal axon has the lowest threshold in response to electric stimulation. Here, we explored whether the anatomical properties of the SOC vary across the ~12 types of ganglion cells. In addition, we explored whether the responses of each type vary.
We measured the ganglion cell response to light in order to classify targeted ganglion cells into known types. Once identified, we used immunochemical staining for voltage-gated sodium channels to identify the size and location of the bands within each type. Finally, we electrically stimulated ganglion cells of the flat mount rabbit retina using a small-tipped Pt-Ir electrode (far-field return) 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.
Different retinal ganglion cell types have distinct SOCs. The length and location were found to be different across the 6 different types we examined (brisk transients(G11, 2 types), G9’s, ON-OFF directionally selective (G7), ON-directionally selective (G10), and local edge detectors (G1)) For example, band lengths for G7’s were 28.9 +/- 6.7 um, while lengths for G11’s were 40.6 +/- 5.4 um. Responses to electrical stimulation were consistent with these band properties. For example, the lowest threshold regions varied across types but were consistent within a given ganglion cell type and always aligned with the SOC.
The SOC differences suggest that band differences may shape the light response of each type. Regions of low threshold were aligned with the SOCs suggesting that the band is a target for stimulation. As band properties vary according to type, the possibility is raised that methods for selective stimulation may be achievable. This would play an important role in improving the quality of elicited percepts during future clinical trials.
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