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Related Experiment Video

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Transfection of Mouse Retinal Ganglion Cells by in vivo Electroporation
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Mediating Retinal Ganglion Cell Spike Rates Using High-Frequency Electrical Stimulation.

Tianruo Guo1, David Tsai1,2,3, Chih Yu Yang1

  • 1Graduate School of Biomedical Engineering, UNSW Sydney, Sydney, NSW, Australia.

Frontiers in Neuroscience
|May 23, 2019
PubMed
Summary

High-frequency electrical stimulation (HFS) shows promise for retinal prosthetics. This study reveals HFS-induced spike inhibition in retinal ganglion cells (RGCs) is linked to membrane hyperpolarization and sodium current properties.

Keywords:
computational modelinghigh-frequency electrical stimulationin vitro patch-clampneuromodulationretinal ganglion cellretinal implant

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Area of Science:

  • Neuroscience
  • Biophysics
  • Biomedical Engineering

Background:

  • Recent retinal studies focus on high-frequency electrical stimulation (>1.0 kHz) for retinal prosthetics.
  • Retinal ganglion cell (RGC) type-specific responses to HFS offer potential for targeted neural stimulation.
  • Ionic mechanisms influencing RGC responses to HFS are not fully understood.

Purpose of the Study:

  • Investigate the ionic mechanisms underlying RGC responses to HFS.
  • Understand how these mechanisms affect RGCs during high-frequency electrical stimulation.
  • Explore the possibility of focally targeting retinal neurons for visual prosthetics.

Main Methods:

  • Developed and utilized an in silico model of RGCs.
  • Calibrated and validated the RGC model using in vitro retinal preparations.
  • Employed a biophysically accurate RGC model with realistic cell morphology.

Main Results:

  • The model successfully replicated stimulus-strength-dependent suppression of RGC action potentials observed experimentally.
  • HFS-induced spike inhibition is attributed to local membrane hyperpolarization from outward currents.
  • Inward sodium current properties significantly alter HFS-induced inhibition.
  • Stimulus-strength-dependent suppression is tunable across various frequencies and electrode placements.

Conclusions:

  • HFS-induced spike inhibition in RGCs is primarily driven by membrane hyperpolarization and influenced by sodium current dynamics.
  • Computational modeling validated by in vitro experiments provides insights into HFS effects on RGCs.
  • This approach can advance understanding of novel stimulation strategies for retinal prosthetics.