Functional Connectivity Map of Retinal Ganglion Cells for Retinal Prosthesis

  • Ye, Jang-Hee (Department of Physiology, Chungbuk National University School of Medicine) ;
  • Ryu, Sang-Baek (Department of Biomedical Engineering, College of Health Science, Yonsei University) ;
  • Kim, Kyung-Hwan (Department of Biomedical Engineering, College of Health Science, Yonsei University) ;
  • Goo, Yong-Sook (Department of Physiology, Chungbuk National University School of Medicine)
  • Published : 2008.12.31

Abstract

Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Among the many issues for prosthesis development, stimulation encoding strategy is one of the most essential electrophysiological issues. The more we understand the retinal circuitry how it encodes and processes visual information, the greater it could help decide stimulation encoding strategy for retinal prosthesis. Therefore, we examined how retinal ganglion cells (RGCs) in in-vitro retinal preparation act together to encode a visual scene with multielectrode array (MEA). Simultaneous recording of many RGCs with MEA showed that nearby neurons often fired synchronously, with spike delays mostly within 1 ms range. This synchronized firing - narrow correlation - was blocked by gap junction blocker, heptanol, but not by glutamatergic synapse blocker, kynurenic acid. By tracking down all the RGC pairs which showed narrow correlation, we could harvest 40 functional connectivity maps of RGCs which showed the cell cluster firing together. We suggest that finding functional connectivity map would be useful in stimulation encoding strategy for the retinal prosthesis since stimulating the cluster of RGCs would be more efficient than separately stimulating each individual RGC.

Keywords

References

  1. Amthor FR, Takahashi ES, Oyster CW. Morphologies of rabbit retinal ganglion cells with concentric receptive fields. J Comp Neurol 280: 72-96, 1989a https://doi.org/10.1002/cne.902800107
  2. Amthor FR, Takahashi ES, Oyster CW. Morphologies of rabbit retinal ganglion cells with complex receptive fields. J Comp Neurol 280: 97-121, 1989b https://doi.org/10.1002/cne.902800108
  3. Arnett D, Spraker TE. Cross-correlation analysis of the maintained discharge of rabbit retinal ganglion cells. J Physiol (London) 317: 29-47, 1981 https://doi.org/10.1113/jphysiol.1981.sp013812
  4. Brivanlou IH, Warland DK, Meister M. Mechanisms of concerted firing among retinal ganglion cells. Neuron 20: 527-539, 1998 https://doi.org/10.1016/S0896-6273(00)80992-7
  5. Brown SP, He S, Masland RH. Receptive field microstructure and dendritic geometry of retinal ganglion cells. Neuron 27: 371-383, 2000 https://doi.org/10.1016/S0896-6273(00)00044-1
  6. Caldwell JH, Daw NW. New properties of rabbit retinal ganglion cells. J Physiol (Lond.) 276: 257-276, 1978 https://doi.org/10.1113/jphysiol.1978.sp012232
  7. DeVries SH, Baylor DA. Mosaic arrangement of ganglion cell receptive fields in rabbit retina. J Neurophysiol 78: 2048-2060, 1997 https://doi.org/10.1152/jn.1997.78.4.2048
  8. DeVries SH. Correlated firing in rabbit retinal ganglion cells. J Neurophysiol 81: 908-920, 1999 https://doi.org/10.1152/jn.1999.81.2.908
  9. Egert U, Schlosshauer B, Fennrich S, Nisch W, Fejtl M, Knott T, Muller T, Hammerle H. A novel organotypic long-term culture of the rat hippocampus on substrate-integrated multielectrode arrays. Brain Res Protoc 2: 229-242, 1998 https://doi.org/10.1016/S1385-299X(98)00013-0
  10. Guenther E, Herrmann T, Stett A. The retina sensor: An in vitro tool to study drug effects on retinal signaling. In: Taketani M, Baudry M, ed, Advances in Network Electrophysiology Using Multi-electrode Arrays. 1st ed. Springer, New York, p 321-331, 2006
  11. Humayun MS, Weiland JD, Fujii GY, Greenberg R, Williamson R, Little J, Mech G, Cimmarusti V, Boemel GV, Dagnelie G, de Juan Jr E. Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vis Res 43: 2573-2581, 2003 https://doi.org/10.1016/S0042-6989(03)00457-7
  12. Lowenstein JI, Montezuma SR, Rizzo III JF. Outer retinal degeneration: an electronic retinal prosthesis as a treatment strategy. Archives of Ophthalmology 122: 588-596, 2004
  13. Margolis DJ, Detwilder PB. Different mechanisms generate maintained activity in ON and OFF retinal ganglion cells. J Neurosci 27: 5994-6005, 2007 https://doi.org/10.1523/JNEUROSCI.0130-07.2007
  14. Mastronarde DN. Interactions between ganglion cells in cat retina. J Neurophysiol 49:350-365, 1983 https://doi.org/10.1152/jn.1983.49.2.350
  15. Meister M, Pine J, Baylor DA. Multi-neuronal signals from the retina: acquisition and analysis. J Neurosci Methods 51: 95-106, 1994 https://doi.org/10.1016/0165-0270(94)90030-2
  16. Meister M, Lagnado L, Baylor DA. Concerted signaling by retinal ganglion cells. Science 270: 1207-1210, 1995 https://doi.org/10.1126/science.270.5239.1207
  17. Meister M. Multineuronal codes in retinal signaling. Proc Natl Acad Sci USA 93: 609-614, 1996
  18. Meister M, Berry MJ 2nd. The neural code of the retina. Neuron 22: 435-450, 1999 https://doi.org/10.1016/S0896-6273(00)80700-X
  19. Nakatani K, Tamura T, Yau KW. Light adaptation in retinal rods of the rabbit and two other nonprimate mammals. J Gen Physiol 97: 413-435, 1991 https://doi.org/10.1085/jgp.97.3.413
  20. Rizzo JF III, Wyatt J, Lowenstein J, Kelly S, Shire D. Perceptual efficacy of electrical stimulation of human retina with a microelectrode array during short-term surgical trials. Invest Ophthalmol Vis Sci 44: 5362-5369, 2003 https://doi.org/10.1167/iovs.02-0817
  21. Seo J, Zhou J, Kim E, Koo K, Ye JH, Kim SJ, Chung H, Cho DD, Goo YS, Yu YS. A retinal implant system based on flexible polymer microelectrode array for electrical stimulation. In: Tombran-Tink J, Barnstable C, Rizzo JF ed, Visual Prosthesis and Ophthalmic Devices: New Hope in Sight. 1st ed. Humana Press Inc, New Jersey, p 107-119, 2007
  22. Stett A, Barth W, Weiss S, Haemmerle H, Zrenner E. Electrical multisite stimulation of isolated chicken retina. Vis Res 40: 1785-1795, 2000 https://doi.org/10.1016/S0042-6989(00)00005-5
  23. Zrenner E, Besch D, Bartz-Schmidt KU, Gekeler F, Gabriel VP, Kuttenkeuler C, Sachs H, Saier H, Wilhelm B, Wilke R. Subretinal chronic multi-electrode arrays implanted in blind patients. Invest Ophthalmol Vis Sci 47: E-Abstract 1538, 2006