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Inner and outer retinal mechanisms engaged by epiretinal stimulation in normal and rd mice

Published online by Cambridge University Press:  04 April 2011

EYAL MARGALIT ,
NORBERT BABAI ,
JIANMIN LUO  and
WALLACE B. THORESON
EYAL MARGALIT*
Affiliation:
VA Nebraska-Western Iowa Health Care System Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska
NORBERT BABAI
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska
JIANMIN LUO
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska
WALLACE B. THORESON
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska
*
†Address correspondence and reprint requests to: Dr. Eyal Margalit, Retina Service, Department of Ophthalmology and Visual Sciences, 985540 Nebraska Medical Center, Omaha, NE 68198-5540. E-mail: [email protected]
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Abstract

Retinal prosthetic devices are being developed to bypass degenerated retinal photoreceptors by directly activating retinal neurons with electrical stimulation. However, the retinal circuitry that is activated by epiretinal stimulation is not well characterized. Whole-cell patch clamp recordings were obtained from ganglion cells in normal and rd mice using flat-mount and retinal slice preparations. A stimulating electrode was positioned along the ganglion cell side of the preparation at different distances from the stimulated tissue. Pulses of cathodic current evoked action potentials in ganglion cells and less frequently evoked sustained inward currents that appeared synaptic in origin. Sustained currents reversed around ECl and were inhibited by blockade of α-amino-3-hydroxyl-5-methyl-4-isoxazole-proprionate (AMPA)-type glutamate receptors with 2,3-dihydroxy-6-nitro-sulfamoyl-benzo(f)-quinoxaline-2,3-dione (NBQX), γ aminobutyric acid a/c (GABAa/c) receptors with picrotoxinin, or glycine receptors with strychnine. This suggests that epiretinal stimulation activates glutamate release from bipolar cell terminals, which in turn evokes release of GABA and glycine from amacrine cells. Synaptic current thresholds were lower in ON ganglion cells than OFF cells, but the modest difference did not attain statistical significance. Synaptic currents were rarely observed in rd mice lacking photoreceptors compared to normal retina. In addition, confocal calcium imaging experiments in normal mice retina slices revealed that epiretinal stimulation evoked calcium increases in the outer plexiform layer. These results imply a contribution from photoreceptor inputs to the synaptic currents observed in ganglion cells. The paucity of synaptic responses in rd mice retina slices suggests that it is better to target retinal ganglion cells directly rather than to attempt to engage the inner retinal circuitry.

Keywords

RetinaElectrical stimulationRetinal prosthesisrd mouseGanglion cell
Type
Research Articles
Information
Visual Neuroscience , Volume 28 , Issue 2 , March 2011 , pp. 145 - 154
Copyright
Copyright © Cambridge University Press 2011

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References

Besch, D., Sachs, H., Szurman, P., Gulicher, D., Wilke, R., Reinert, S., Zrenner, E., Bartz-Schmidt, K.U. & Gekeler, F. (2008). Extraocular surgery for implantation of an active subretinal visual prosthesis with external connections: Feasibility and outcome in seven patients. The British Journal of Ophthalmology 92, 1361–1368.CrossRefGoogle ScholarPubMed
Chen, S.J., Mahadevappa, M., Roizenblatt, R., Weiland, J. & Humayun, M. (2006). Neural responses elicited by electrical stimulation of the retina. Transactions of the American Ophthalmological Society 104, 252–259.Google ScholarPubMed
Cogan, S.F., Guzelian, A.A., Agnew, W.F., Yuen, T.G. & McCreery, D.B. (2004). Over-pulsing degrades activated iridium oxide films used for intracortical neural stimulation. Journal of Neuroscience Methods 137, 141–150.CrossRefGoogle ScholarPubMed
Fried, S.I., Hsueh, H.A. & Werblin, F.S. (2006). A method for generating precise temporal patterns of retinal spiking using prosthetic stimulation. Journal of Neurophysiology 95, 970–978.CrossRefGoogle ScholarPubMed
Fried, S.I., Lasker, A.C., Desai, N.J., Eddington, D.K. & Rizzo, J.F. III (2009). Axonal sodium-channel bands shape the response to electric stimulation in retinal ganglion cells. Journal of Neurophysiology 101, 1972–1987.CrossRefGoogle ScholarPubMed
Greenberg, R.J. (1998). Analysis of electrical stimulation of the vertebrate retina—work towards a retinal prosthesis. Doctoral Thesis, The Johns Hopkins University, Baltimore, MD.Google Scholar
Grumet, A.E., Wyatt, J.L. & Rizzo, J.F. (2000). Multi-electrode stimulation and recording in the isolated retina. Journal of Neuroscience Methods 101, 31–42.CrossRefGoogle ScholarPubMed
Humayun, M., Propst, R., de Juan, E. Jr, McCormick, K. & Hickingbotham, D. (1994). Bipolar surface electrical stimulation of the vertebrate retina. Archives of Ophthalmology 112, 110–116.CrossRefGoogle ScholarPubMed
Jensen, R.J. & Rizzo, J.F. III (2006). Thresholds for activation of rabbit retinal ganglion cells with a subretinal electrode. Experimental Eye Research 83, 367–373.CrossRefGoogle ScholarPubMed
Jensen, R.J. & Rizzo, J.F. III (2008). Activation of retinal ganglion cells in wild-type and rd1 mice through electrical stimulation of the retinal neural network. Vision Research 48, 1562–1568.CrossRefGoogle ScholarPubMed
Jensen, R.J. & Rizzo, J.F. III (2009). Activation of ganglion cells in wild-type and rd1 mouse retinas with monophasic and biphasic current pulses. Journal of Neural Engineering 6, 035004.CrossRefGoogle ScholarPubMed
Jensen, R.J., Ziv, O.R. & Rizzo, J.F. (2005 a). Responses of rabbit retinal ganglion cells to electrical stimulation with an epiretinal electrode. Journal of Neural Engineering 2, S16–S21.CrossRefGoogle ScholarPubMed
Jensen, R.J., Ziv, O.R. & Rizzo, J.F. III (2005 b). Thresholds for activation of rabbit retinal ganglion cells with relatively large, extracellular microelectrodes. Investigative Ophthalmology & Visual Science 46, 1486–1496.CrossRefGoogle ScholarPubMed
Jeon, C.J., Strettoi, E. & Masland, R.H. (1998). The major cell populations of the mouse retina. The Journal of Neuroscience 18, 8936–8946.CrossRefGoogle ScholarPubMed
Jones, B.W. & Marc, R.E. (2005). Retinal remodeling during retinal degeneration. Experimental Eye Research 81, 123–137.CrossRefGoogle ScholarPubMed
Knighton, R.W. (1975 a). An electrically evoked slow potential of the frog’s retina. I. Properties of response. Journal of Neurophysiology 38, 185–197.CrossRefGoogle ScholarPubMed
Knighton, R.W. (1975 b). An electrically evoked slow potential of the frog’s retina. II. Identification with PII component of electroretinogram. Journal of Neurophysiology 38, 198–209.CrossRefGoogle ScholarPubMed
Margalit, E., Maia, M., Weiland, J.D., Greenberg, R.J., Fujii, G.Y., Torres, G., Piyathaisere, D.V., O’Hearn, T.M., Liu, W., Lazzi, G., Dagnelie, G., Scribner, D.A., de Juan, E. Jr. & Humayun, M.S. (2002). Retinal prosthesis for the blind. Survey of Ophthalmology 47, 335–356.CrossRefGoogle ScholarPubMed
Margalit, E. & Thoreson, W.B. (2006). Inner retinal mechanisms engaged by retinal electrical stimulation. Investigative Ophthalmology & Visual Science 47, 2606–2612.CrossRefGoogle ScholarPubMed
Margolis, D.J., Newkirk, G., Euler, T. & Detwiler, P.B. (2008). Functional stability of retinal ganglion cells after degeneration-induced changes in synaptic input. The Journal of Neuroscience 28, 6526–6536.CrossRefGoogle ScholarPubMed
Murashima, Y.L., Ishikawa, T. & Kato, T. (1990). gamma-Aminobutyric acid system in developing and degenerating mouse retina. Journal of Neurochemistry 54, 893–898.CrossRefGoogle ScholarPubMed
O’Hearn, T.M., Sadda, S.R., Weiland, J.D., Maia, M., Margalit, E. & Humayun, M.S. (2006). Electrical stimulation in normal and retinal degeneration (rd1) isolated mouse retina. Vision Research 46, 3198–3204.CrossRefGoogle ScholarPubMed
Pang, J.J., Gao, F. & Wu, S.M. (2002). Relative contributions of bipolar cell and amacrine cell inputs to light responses of ON, OFF and ON-OFF retinal ganglion cells. Vision Research 42, 19–27.CrossRefGoogle Scholar
Ranck, J.B. Jr. (1975). Which elements are excited in electrical stimulation of mammalian central nervous system: A review. Brain Research 98, 417–440.CrossRefGoogle ScholarPubMed
Sekirnjak, C., Hottowy, P., Sher, A., Dabrowski, W., Litke, A.M. & Chichilnisky, E.J. (2006). Electrical stimulation of mammalian retinal ganglion cells with multielectrode arrays. Journal of Neurophysiology 95, 3311–3327.CrossRefGoogle ScholarPubMed
Shah, H.A., Montezuma, S.R. & Rizzo, J.F. III (2006). In vivo electrical stimulation of rabbit retina: Effect of stimulus duration and electrical field orientation. Experimental Eye Research 83, 247–254.CrossRefGoogle ScholarPubMed
Stasheff, S.F. (2008). Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse. Journal of Neurophysiology 99, 1408–1421.CrossRefGoogle ScholarPubMed
Stett, A., Barth, W., Weiss, S., Haemmerle, H. & Zrenner, E. (2000). Electrical multisite stimulation of the isolated chicken retina. Vision Research 40, 1785–1795.CrossRefGoogle ScholarPubMed
Suzuki, S., Humayun, M.S., Weiland, J.D., Chen, S.J., Margalit, E., Piyathaisere, D.V. & de Juan, E. Jr. (2004). Comparison of electrical stimulation thresholds in normal and retinal degenerated mouse retina. Japanese Journal of Ophthalmology 48, 345–349.CrossRefGoogle ScholarPubMed
Thoreson, W.B. & Miller, R.F. (1993). Membrane currents evoked by excitatory amino acid agonists in ON bipolar cells of the mudpuppy retina. Journal of Neurophysiology 70, 1326–1338.CrossRefGoogle Scholar
Tsai, D., Morley, J.W., Suaning, G.J. & Lovell, N.H. (2009). Direct activation of retinal ganglion cells with subretinal stimulation. Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society 2009, 618–621.Google ScholarPubMed
Wang, P. & Slaughter, M.M. (2005). Effects of GABA receptor antagonists on retinal glycine receptors and on homomeric glycine receptor alpha subunits. Journal of Neurophysiology 93, 3120–3126.CrossRefGoogle ScholarPubMed
Werblin, F.S. (1978). Transmission along and between rods in the tiger salamander retina. The Journal of Physiology 280, 449–470.CrossRefGoogle ScholarPubMed
Wu, S.M. (1987). Synaptic connections between neurons in living slices of the larval tiger salamander retina. Journal of Neuroscience Methods 20, 139–149.CrossRefGoogle ScholarPubMed
Yanai, D., Weiland, J.D., Mahadevappa, M., Greenberg, R.J., Fine, I. & Humayun, M.S. (2007). Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa. American Journal of Ophthalmology 143, 820–827.CrossRefGoogle ScholarPubMed
Yazulla, S., Studholme, K.M. & Pinto, L.H. (1997). Differences in the retinal GABA system among control, spastic mutant and retinal degeneration mutant mice. Vision Research 37, 3471–3482.CrossRefGoogle ScholarPubMed
Ye, J.H. & Goo, Y.S. (2007 a). Comparison of voltage parameters for the stimulation of normal and degenerate retina. Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society 2007, 5783–5786.Google ScholarPubMed
Ye, J.H. & Goo, Y.S. (2007 b). The slow wave component of retinal activity in rd/rd mice recorded with a multi-electrode array. Physiological Measurement 28, 1079–1088.CrossRefGoogle ScholarPubMed