title: Selectivity of direct and network-mediated stimulation of the retinal ganglion cells with epi-, sub- and intraretinal electrodes.
abstract: OBJECTIVE
  Intra-retinal placement of stimulating electrodes can provide close and stable proximity to target neurons. We assessed improvement in stimulation thresholds and selectivity of the direct and network-mediated retinal stimulation with intraretinal electrodes, compared to epiretinal and subretinal placements.
  
  
  METHODS
  Stimulation thresholds of the retinal ganglion cells (RGCs) in wild-type rat retina were measured using the patch-clamp technique. Direct and network-mediated responses were discriminated using various synaptic blockers.
  
  
  RESULTS
  Three types of RGC responses were identified: short latency (SL, τ < 5 ms) originating in RGCs, medium latency (ML, 3 < τ < 70 ms) originating in the inner nuclear layer and long latency (LL, τ > 40 ms) originating in photoreceptors. Cathodic epiretinal stimulation exhibited the lowest threshold for direct RGC response and the highest direct selectivity (network/direct thresholds ratio), exceeding a factor of 3 with pulse durations below 0.5 ms. For network-mediated stimulation, the lowest threshold was obtained with anodic pulses in OPL position, and its network selectivity (direct/network thresholds ratio) increased with pulse duration, exceeding a factor of 4 at 10 ms. Latency of all three types of responses decreased with increasing strength of the stimulus.
  
  
  CONCLUSIONS
  These results define the optimal range of pulse durations, pulse polarities and electrode placement for the retinal prostheses aiming at direct or network-mediated stimulation of RGCs.
authors.affiliation: Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA 94305, USA. Department of Physics, Stanford University, Stanford, CA 94305, USA.
authors.forename: David
authors.initials: D
authors.lastname: Boinagrov
authors.forename: Susanne
authors.initials: S
authors.lastname: Pangratz-Fuehrer
authors.forename: Georges
authors.initials: G
authors.lastname: Goetz
authors.forename: Daniel
authors.initials: D
authors.lastname: Palanker
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004558:Electric Stimulation / Q000295:instrumentation / Q000379:methods; D004567:Electrodes, Implanted; D008297:Male; D008839:Microelectrodes; D009415:Nerve Net / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D012165:Retinal Ganglion Cells / Q000502:physiology*