Focal activation of retinal ganglion cells with epiretinal implants: The AIS as a key component

Abstract

Purpose : A modeling study was conducted to examine how the low-threshold region of axon initial segments (AIS) can be utilized to focally stimulate the ganglion cell (GC) layer with epiretinal implants.

Methods : The model neuron was derived from the morphology of a mouse OFF GC. Transmembrane currents were computed with a Hodgkin-Huxley type model using a backward Euler integrator. Low- and high-threshold sodium channels were incorporated with specific distributions along the axon. External potentials evoked by a monopolar disc electrode were calculated by the method of finite elements.

Results : The response of multiple closely neighbored GCs elicited by 0.1ms cathodic pulses was computed. Activation thresholds were compared to the threshold of a passing axon from a GC located 400μm away. Thresholds for multiple neurons having their AIS close to the stimulating electrode were lower than threshold for the passing axon (3.18μA for a 20μm disc electrode diameter variation of passing axon (0.5,1,2μm caused 30,18,11 focally activated GCs). In contrast, the region which can be focally activated is rather independent of size of small electrodes (10,20,40μm disc diameter resulted in 18,19,20 focally activated GCs).

Conclusions : According to the model assumption of about 2500 GCs per mm² the low-threshold region in the proximity of the AIS can be utilized for direct stimulation of about 20 GCs close to the electrode without eliciting spikes in bypassing axons. Focal stimulation is not sensitive to electrode size but rather to the GC’s axon diameter. Further investigations of GC properties will be needed to explore how threshold variations depend on different GC types.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

A: Top view of multiple densely packed GCs and one far distant GC are activated at different thresholds by a disc electrode (diameter 20μm,filled red circle). Spacing between the cells was 20μm in x-direction and GC columns were shifted in 5μm steps vertically. Inset: Model GC in 3D view. B: Activation threshold for each GC location is marked in the somas of the GCs. One passing axon with its soma 400μm distant to the electrode has a spiking threshold of 3.18μA. 18 GCs (red) have lower thresholds than the passing axon and can therefore be focally activated. The grey shaded region indicates GC locations with thresholds lower than of the passing axon. The AIS region is indicated by purple bars. Pulse length: 0.1ms; electrode 30μm above the axon.