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P. Werginz, J. Encke, A. Jalligampala, D. Rathbun, F. Rattay:
"Modeled direct and indirect activation of retinal ganglion cells during subretinal stimulation";
Poster: ARVO Meeting 2015, Denver, Colorado; 2015-05-02 - 2015-05-07; in: "Investigative Ophthalmology & Visual Science", 56 (2015).

Purpose:
Although several experimental studies have been performed, it is still unclear how an applied electric potential activates retinal ganglion cells (GC) in detail. This modeling study tries to reveal how direct and indirect (synaptic) activation of GCs can be achieved during subretinal stimulation.

Methods:
We combined models of a bipolar cell (BC), a GC and a connecting ribbon synapse. Cell geometry data was either extracted from 2D depictions from the literature and converted into 3D cell models or taken from a database (www.neuromorpho.org) and further modified. Hodgkin-Huxley-like membrane kinetics were incorporated into the multi-compartment models. Calculations of the membrane potential, synaptic activity, ionic currents etc. were performed in MatLab. External potentials evoked by a monopolar disc electrode were modeled using finite element software COMSOL Multiphysics.

Results:
Responses of the model neurons to 1ms and 5ms pulses were computed for 3 different electrode locations (directly under the somas (Fig); 100um and 300um shifted in x-direction). Both pulse durations were able to trigger direct and indirect spikes. Because of the kinetic characteristics of the ribbon synapse longer pulses preferably activate the BC. For electrode positions closer to the soma, indirect stimulation thresholds are lower than direct activation thresholds. Depending on electrode location either cathodic or anodic pulses result in lower thresholds.

Conclusions:
Modeled activation thresholds are comparable to actual applied stimuli in current retinal implants (0.2-1.5V). Furthermore, the site of spike initiation is heavily depending on the GC morphology. Up to now, no general assumptions can be made how each activation mechanism can be triggered by specific stimulus protocols. Further investigations and more detailed cell models will help to gain deeper insight into activation characteristics.

Retinal implant, Electric stimulation, Computer simulation