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

Abstract

Electric stimulation using retinal implants allows blind people to re-experience a rudimentary kind of vision. The elicited percepts or so called ’phosphenes’ are highly inconstant and therefore do not restore vision properly. The better knowledge of how retinal neurons, especially retinal ganglion cells, respond to electric stimulation will help to develop more sophisticated stimulation strategies. Special anatomic and physiologic properties like a band of highly dense sodium channels in retinal ganglion cells may help to achieve a focal activation of target cells and as a result better restoration of vision. A portion of retinal ganglion cell axons, about 40 μm from the soma and between 25 and 40μm in length, shows a specific biophysical property. Electrode locations close to a band of highly dense sodium channels which was identified immunochemically show lowest thresholds during electric stimulation. The (modeled) thresholds for this kind of structure result in lowest thresholds as well. The influence on the location where action potentials are generated within the axon is far reaching. When a stimulating electrode is positioned far outside the actual band region the site of spike initiation still remains within the sodium channel band. These findings suggest to further examine the key mechanisms of activation for retinal ganglion cells because focal activation without influencing passing axons of neurons located far away can improve the outcome of electric stimulation and therefore the development of retinal implants.

High-Resolution Multi-Scale Computational Model for Non-Invasive Cervical Vagus Nerve Stimulation

“…We developed an approach whereby we modeled rheobase thresholds, namely the response to a long duration pulse. This allowed us, as a first approximation, to remove considerations of neuron dynamics and stimulation train parameters such a number, pulse shape, frequency, and duty‐cycle which while important would incur a large set of additional fiber specific parameterizations —whereas our focus was to address the role of tissue modeling. The assumption also supports future efforts to optimize stimulation approaches leveraging linearity (see “Discussion” section).…”

Minimizing activation of overlying axons with epiretinal stimulation: The role of fiber orientation and electrode configuration

“…As a result of this structure, epiretinal electrical stimulation faces the challenge of stimulating the deeper, favourably-organized GCL while minimizing activation of axons of passage (AOPs) in the NFL. Irregular visual percept shapes are commonly described by recipients of epiretinal implants due to stimulation of axons of passage [13,15,20,21]. This effect has been confirmed experimentally and in simulations, and results in a reduction in the spatial selectivity of epiretinal stimulation [11,[15][16][17][20][21][22].…”

“…7 shows that by recruiting more stimulating electrodes the induced area activated becomes greater, it should be noted that this will not necessarily reduce perceived resolution. Previously, recipients of epiretinal implants have reported elongated and line-like phosphenes, thought to be caused by stimulation of passing axons in the NFL that originate from distant regions of the GCL [1,[11][12][13][14][15][16][17][18][19]. Hence, despite an increase in the region of activation in the GCL when using a four-electrode stimulation strategy, the overall resolution is expected to increase due to the elimination of activation of the NFL.…”

“…In previous models, the low threshold of the AIS has only been incorporated into active, conductance-based models of RGCs. In these models, the threshold is reduced at the AIS by increasing the sodium channel density by a factor ranging from 2 to 40, generally chosen to reproduce desired physiological responses [15,19,51].…”

“…Although progress to date is highly encouraging, many aspects of the performance of retinal prostheses remain limited, hinging on the ability of these devices to target either specific retinal cell types [9,10] or more precise retinal volumes [1,3,11]. In the case of epiretinal stimulation, a factor limiting performance is the inability of electrical stimulation to preferentially activate target neuronal structures in the ganglion cell layer (GCL) while avoiding activation of overlying axons in the nerve fiber layer (NFL) [1,[11][12][13][14][15][16][17][18][19], illustrated in Fig. 1.…”