gms | German Medical Science

The selective activation of major retinal ganglion cell (RGC) types constitutes a key goal of the stimulation paradigms used by retinal prosthetics as it can greatly enhance the quality of visual perception that can be restored to the blind. Recent work demonstrated that ON and OFF RGC spike rates can be modulated in opposing directions by high-frequency (2 kHz) pulsatile stimulation, suggesting a possible means for selective activation of individual types. We want to better understand the neural mechanisms that underlie this differential activation and hypothesize that they arise from differential expression of voltage-gated sodium channels (Nav) within the sodium channel band (SCB) on the initial segment, e.g. each type of ganglion cell has a unique configuration of sodium channels. Within the ganglion cell there are two major types of Nav that are spatially segregated: Nav1.1 channels are located on the proximal portion of the SCB while Nav1.6 are on the distal portion. The two types are known to play distinct roles in the generation of neuronal activity and have differing sensitivity to electrical stimulation. In the present work we investigate the properties of the SCB by a high-resolution mapping of the RGC sensitivity to low-frequency (10 Hz) pulse trains, e.g. how threshold varies with the position of the stimulating electrode. The boundaries of the “threshold maps” are coextensive with the SCB and reveal details of the SCB sub-components. We then compare the properties of the SCB with the ability to sustain electrical stimulation at high frequencies (1–5 kHz). This work will ultimately be aimed at determining the nature of surviving RGC types in the diseased retina to inform a more effective stimulation paradigm for next-generation retinal prostheses.