title: Indirect activation elicits strong correlations between light and electrical responses in ON but not OFF retinal ganglion cells.
abstract: CONCLUSIONS
  To improve the quality of vision elicited by retinal prosthetics, elicited neural activity should resemble physiological signalling patterns; here, we hypothesized that electric stimulation that activates the synaptic circuitry of the retina would lead to closer matches than that which activates ganglion cells directly. We evaluated this hypothesis by comparing light and electrical responses in different types of ganglion cells. In contrast to the similarity in their light responses, electrical responses in ON and OFF cells of the same type were quite distinct. Further, electrical and light responses in the same cell were much better correlated in ON vs. OFF ganglion cells. Stimuli that activated photoreceptors yielded better correlations than those which activated bipolar cells. Our results suggest that the closer match to physiology in the ON signal transmitted to the brain may help to explain preferential reports of 'bright' phosphenes during earlier clinical trials.
  To improve the efficacy of microelectronic retinal prosthetics it will be necessary to better understand the response of retinal neurons to electric stimulation. While stimulation that directly activates ganglion cells generally has the lowest threshold, the similarity in responsiveness across cells makes it extremely difficult for such an approach to re-create cell-type specific patterns of neural activity that arise normally in the healthy retina. In contrast, stimulation that activates neurons presynaptic to ganglion cells utilizes at least some of the existing retinal circuitry and therefore is thought to produce neural activity that better matches physiological signalling. Surprisingly, the actual benefit(s) of this approach remain unsubstantiated. Here, we recorded from ganglion cells in the rabbit retinal explant in response to electrical stimuli that activated the network. Targeted cells were first classified into known types via light responses so that the consistency of electrical responses within individual types could be evaluated. Both transient and sustained ON ganglion cells exhibited highly consistent electrical response patterns which were distinct from one another. Further, properties of the response (interspike interval, latency, peak firing rate, and spike count) in a given cell were well correlated to the corresponding properties of the light response for that same cell. Electric responses in OFF ganglion cells formed two groups, distinct from ON groups, and the correlation levels between electric and light responses were much weaker. The closer match in ON pathway responses may help to explain some preferential reporting of bright stimuli during psychophysical testing.
authors.affiliation: Veterans Affairs Boston Healthcare System, 150 South Huntington Avenue, Boston, MA, 02130, USA.|Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, MA, 02114, USA.
authors.forename: Maesoon
authors.initials: M
authors.lastname: Im
authors.affiliation: Veterans Affairs Boston Healthcare System, 150 South Huntington Avenue, Boston, MA, 02130, USA.|Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, 50 Blossom Street, Boston, MA, 02114, USA.
authors.forename: Shelley I
authors.initials: SI
authors.lastname: Fried
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D010775:Photic Stimulation; D011817:Rabbits; D012165:Retinal Ganglion Cells / Q000502:physiology*