The sodium channel band shapes the response to electric stimulation in retinal ganglion cells

Abstract

To improve the quality of prosthetic vision, it is desirable to understand how targeted retinal neurons respond to stimulation. Unfortunately, the factors that shape the response of a single neuron to stimulation are not well understood. A dense band of voltage gated sodium channels within the proximal axon of retinal ganglion cells is the site most sensitive to electric stimulation, suggesting that band properties are likely to influence the response to stimulation. Here, we examined how three band properties influence sensitivity using a morphologically realistic ganglion cell model in NEURON. Longer bands were more sensitive to short-duration pulses than shorter bands and increasing the distance between band and soma also increased sensitivity. Simulations using the known limits of band length and location resulted in a sensitivity difference of approximately two. Additional simulations tested how changes to sodium channel conductance within the band influenced threshold and found that the sensitivity difference increased to a factor of nearly three. This is close to the factor of 5 difference measured in physiological studies suggesting that band properties contribute significantly to the sensitivity differences found between different types of retinal neurons.

Responses of Retinal Ganglion Cells to Extracellular Electrical Stimulation, from Single Cell to Population: Model-Based Analysis

“…boxed region in Figure 1D1 and 1E1) and the axons also formed a low threshold corridor. These results are consistent with experimental observations [32] and recent theoretical predictions [33]. Less well understood is the RGC threshold around the dendro-somatic axis.…”

“…Our threshold maps (e.g. Figure 1) are consistent with experimental findings of Fried [32] and simulation work of Jeng et al [33]. An earlier threshold mapping study by Jensen [17] reported a more fragmented map, which is reminiscent of our results on midget RGCs stimulated with large electrodes.…”

The effect of morphology upon electrophysiological responses of retinal ganglion cells: simulation results

“…This is supported by recent evidence showing the existence of a low threshold region consisting of a dense band of voltage-gated sodium channels in the initial portion of the RGC axon (Fried et al 2009; Jeng et al 2011). This band is located 38.8 ±10 μ m from the soma, with a mean length of 36.8 ± 5.6 μ m. The exact concentration of sodium in the SOCB in RGCs is unclear.…”

Influence of the sodium channel band on retinal ganglion cell excitation during electric stimulation – A modeling study

“…B.2A and methods section ’Three-layer model vs. Seven-layer model’). The electrode was embedded in an ames solution which had an isotropic electric resistivity of 1.1Ω·m (Jeng et al (2011)). As electrode material we chose Platinum (electric resistivity: 1.05·10 −7 Ω·m (Comsol Multiphysics Material Library)), the modeled electrode geometry was the same as used by Fried et al: a cone shaped electrode, 30μm in base diameter and 35μm in height.…”

“…Jensen et al (2003); Sekirnjak et al (2006, 2008); Cai et al (2011); Eickenscheidt et al (2012)) but only few modeling studies (e.g. Jeng et al (2011); Tsai et al (2012)) have been performed to enlighten the recruitment order of the electrically stimulated retinal circuitry.…”