title: Retinal ganglion cells: mechanisms underlying depolarization block and differential responses to high frequency electrical stimulation of ON and OFF cells.
abstract: OBJECTIVE
  ON and OFF retinal ganglion cells (RGCs) are known to have non-monotonic responses to increasing amplitudes of high frequency (2 kHz) biphasic electrical stimulation. That is, an increase in stimulation amplitude causes an increase in the cell's spike rate up to a peak value above which further increases in stimulation amplitude cause the cell to decrease its activity. The peak response for ON and OFF cells occurs at different stimulation amplitudes, which allows differential stimulation of these functional cell types. In this study, we investigate the mechanisms underlying the non-monotonic responses of ON and OFF brisk-transient RGCs and the mechanisms underlying their differential responses.
  
  
  METHODS
  Using in vitro patch-clamp recordings from rat RGCs, together with simulations of single and multiple compartment Hodgkin-Huxley models, we show that the non-monotonic response to increasing amplitudes of stimulation is due to depolarization block, a change in the membrane potential that prevents the cell from generating action potentials.
  
  
  RESULTS
  We show that the onset for depolarization block depends on the amplitude and frequency of stimulation and reveal the biophysical mechanisms that lead to depolarization block during high frequency stimulation. Our results indicate that differences in transmembrane potassium conductance lead to shifts of the stimulus currents that generate peak spike rates, suggesting that the differential responses of ON and OFF cells may be due to differences in the expression of this current type. We also show that the length of the axon's high sodium channel band (SOCB) affects non-monotonic responses and the stimulation amplitude that leads to the peak spike rate, suggesting that the length of the SOCB is shorter in ON cells.
  
  
  CONCLUSIONS
  This may have important implications for stimulation strategies in visual prostheses.
authors.affiliation: NeuroEngineering Laboratory, Department of Electrical and Electronic Engineering, The University of Melbourne, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Kameneva
authors.forename: M I
authors.initials: MI
authors.lastname: Maturana
authors.forename: A E
authors.initials: AE
authors.lastname: Hadjinicolaou
authors.forename: S L
authors.initials: SL
authors.lastname: Cloherty
authors.forename: M R
authors.initials: MR
authors.lastname: Ibbotson
authors.forename: D B
authors.initials: DB
authors.lastname: Grayden
authors.forename: A N
authors.initials: AN
authors.lastname: Burkitt
authors.forename: H
authors.initials: H
authors.lastname: Meffin
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D003198:Computer Simulation; D004056:Differential Threshold / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods*; D008564:Membrane Potentials / Q000502:physiology*; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D015203:Reproducibility of Results; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D012680:Sensitivity and Specificity