Electrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons

PLoS Comput Biol. 2018 Feb 12;14(2):e1005997. doi: 10.1371/journal.pcbi.1005997. eCollection 2018 Feb.

Abstract

Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases. Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation. Due to these complexities, most existing implants activate only a few electrodes at a time, limiting the repertoire of available stimulation patterns. Measuring the spatiotemporal interactions between electrodes and retinal cells, and incorporating them into a model may lead to improved stimulation algorithms that exploit the interactions. Here, we present a computational model that accurately predicts both the spatial and temporal nonlinear interactions of multi-electrode stimulation of rat retinal ganglion cells (RGCs). The model was verified using in vitro recordings of ON, OFF, and ON-OFF RGCs in response to subretinal multi-electrode stimulation with biphasic pulses at three stimulation frequencies (10, 20, 30 Hz). The model gives an estimate of each cell's spatiotemporal electrical receptive fields (ERFs); i.e., the pattern of stimulation leading to excitation or suppression in the neuron. All cells had excitatory ERFs and many also had suppressive sub-regions of their ERFs. We show that the nonlinearities in observed responses arise largely from activation of presynaptic interneurons. When synaptic transmission was blocked, the number of sub-regions of the ERF was reduced, usually to a single excitatory ERF. This suggests that direct cell activation can be modeled accurately by a one-dimensional model with linear interactions between electrodes, whereas indirect stimulation due to summated presynaptic responses is nonlinear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Algorithms
  • Animals
  • Computer Simulation*
  • Electric Stimulation
  • Electrodes
  • Light
  • Models, Neurological
  • Neurons / physiology*
  • Presynaptic Terminals / physiology*
  • Rats
  • Reproducibility of Results
  • Retina / physiology
  • Retinal Ganglion Cells / physiology*
  • Signal-To-Noise Ratio
  • Software
  • Synapses / physiology
  • Vision, Ocular
  • Visual Cortex / physiology

Grants and funding

This research was supported by the National Health and Medical Research Council, Project Grant (https://www.nhmrc.gov.au/). HM and MRI acknowledge supported through the Australian Research Council, Centre of Excellence for Integrative Brain Function (CE140100007, http://www.arc.gov.au/arc-centre-excellence-integrative-brain-function). ANB and TK acknowledge support through the Australian Research Council Discovery Projects funding scheme (DP140104533; http://www.arc.gov.au/). DJG and NVP are supported by National Health and Medical Research Council grant (GNT1101717, https://www.nhmrc.gov.au/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.