title: Temporal properties of network-mediated responses to repetitive stimuli are dependent upon retinal ganglion cell type.
abstract: OBJECTIVE
  To provide artificially-elicited vision that is temporally dynamic, retinal prosthetic devices will need to repeatedly stimulate retinal neurons. However, given the diversity of physiological types of retinal ganglion cells (RGCs) as well as the heterogeneity of their responses to electric stimulation, temporal properties of RGC responses have not been adequately investigated. Here, we explored the cell type dependence of network-mediated RGC responses to repetitive electric stimulation at various stimulation rates.
  
  
  METHODS
  We examined responses of ON and OFF types of RGCs in the rabbit retinal explant to five consecutive stimuli with varying inter-stimulus intervals (10-1000 ms). Each stimulus was a 4 ms long monophasic sinusoidal cathodal current, which was applied epiretinally via a conical electrode. Spiking activity of targeted RGCs was recorded using a cell-attached patch electrode.
  
  
  RESULTS
  ON and OFF cells had distinct responses to repetitive stimuli. Consistent with earlier studies, OFF cells always generated reduced responses to subsequent stimuli compared to responses to the first stimulus. In contrast, a new stimulus to ON cells suppressed all pending/ongoing responses from previous stimuli and initiated its own response that was remarkably similar to the response from a single stimulus in isolation. This previously unreported 'reset' behavior was observed exclusively and consistently in ON cells. These contrasts between ON and OFF cells created a range of stimulation rates (4-7 Hz) that maximized the ratio of the responses arising in ON versus OFF cells.
  
  
  CONCLUSIONS
  Previous clinical testing reported that subjects perceive bright phosphenes (ON responses) and also prefer stimulation rates of 5-7 Hz. Our results suggest that responses of ON cells are weak at high rates of stimulation (> ∼7 Hz) due to the reset while responses of OFF cells are strong at low rates (< ∼4 Hz) due to reduced desensitization, both reducing the ratio of ON to OFF responses. In combination with previous results indicating that responses in ON cells more closely match physiological patterns (Im and Fried 2015 J. Physiol. 593 3577-96), our results offer a potential reason for the user preference of intermediate rates (5-7 Hz).
authors.affiliation: VA Boston Healthcare System, 150 South Huntington Avenue, Boston, MA 02130, USA. Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, 50 Blossom Street, Boston, MA 02114, USA. Present address: Department of Ophthalmology, Henry Ford Hospital, 1 Ford Place, Detroit, MI 48202, USA.
authors.forename: Maesoon
authors.initials: M
authors.lastname: Im
authors.forename: Shelley I
authors.initials: SI
authors.lastname: Fried
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D009415:Nerve Net / Q000502:physiology*; D010775:Photic Stimulation / Q000379:methods*; D011817:Rabbits; D011930:Reaction Time / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology*