April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Ganglion Cell Desensitization To Repetitive Stimulation Correlates With Brightness Fading In Human Subjects
Author Affiliations & Notes
  • Daniel K. Freeman
    Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Somerville, Massachusetts
    Center for Innovative Visual Rehabilitation, Boston VA Healthcare System, Boston, Massachusetts
  • Shelley I. Fried
    Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Somerville, Massachusetts
    Center for Innovative Visual Rehabilitation, Boston VA Healthcare System, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Daniel K. Freeman, None; Shelley I. Fried, None
  • Footnotes
    Support  Career Development Award CDA-1
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4583. doi:
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      Daniel K. Freeman, Shelley I. Fried; Ganglion Cell Desensitization To Repetitive Stimulation Correlates With Brightness Fading In Human Subjects. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4583.

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Abstract

Purpose: : In response to repetitive electrical stimulation of the retina, blind subjects report that brightness fades rapidly, within several hundreds of milliseconds, as well as over many seconds. The objective here is to determine whether this perceptual phenomenon may be retinal in origin. We do this by comparing the time course of ganglion cell desensitization due to repetitive stimulation of the retina to the reported time course of brightness fading seen in blind human subjects implanted with a retinal prosthetic.

Methods: : Cell-attached patch clamping was used to record spike trains from rabbit retinal ganglion cells in response to electrical stimulation from a small stimulating electrode (10kOhm, Pt-Ir) positioned directly over the soma. Pulse trains were delivered at 2-16Hz (pulse duration, 1ms) for up to 20sec. The number of synaptically mediated spikes was examined over time for the duration of stimulation.

Results: : In response to repetitive electrical stimulation of the retina, ganglion cells exhibit two phases of desensitization, one occurring rapidly and acting within hundreds of milliseconds (tau = 176.4 ± 8.8ms), the other acting much slower, over many seconds (tau = 14.0 ± 1.1sec). Desensitization persists in the presence of inhibitory blockers (strychnine and picrotoxin), indicating amacrine cell inhibition is not required for desensitization. The threshold for direct activation of the ganglion cell changes little during the simultaneous desensitization of the synaptically mediated response, indicating that (1) desensitization likely occurs upstream of the spike generator, and (2) stimulation targeting the ganglion cell directly can still be achieved even during suppression of the synaptically mediated response.

Conclusions: : The two phases of ganglion cell desensitization match the two phases of brightness fading seen in human subjects. This suggests that the fading of visual percepts over time in human subjects may be a direct result of reduced ganglion cell firing, and may not involve saccadic eye movements or aberrant processing in higher visual centers.

Keywords: retina • electrophysiology: non-clinical • ganglion cells 
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