title: Differential targeting of optical neuromodulators to ganglion cell soma and dendrites allows dynamic control of center-surround antagonism.
abstract: Retinal degenerative diseases cause photoreceptor loss and often result in remodeling and deafferentation of the inner retina. Fortunately, ganglion cell morphology appears to remain intact long after photoreceptors and distal retinal circuitry have degenerated. We have introduced the optical neuromodulators channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR) differentially into the soma and dendrites of ganglion cells to recreate antagonistic center-surround receptive field interactions. We then reestablished the physiological receptive field dimensions of primate parafoveal ganglion cells by convolving Gaussian-blurred versions of the visual scene at the appropriate wavelength for each neuromodulator with the Gaussians inherent in the soma and dendrites. These Gaussian-modified ganglion cells responded with physiologically relevant antagonistic receptive field components and encoded edges with parafoveal resolution. This approach bypasses the degenerated areas of the distal retina and could provide a first step in restoring sight to individuals suffering from retinal disease.
authors.affiliation: Department of Molecular and Cell Biology, Division of Neurobiology, University of California, Berkeley, Berkeley, CA 94720-3200, USA. kgreenb@berkeley.edu
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Greenberg
authors.forename: Aaron
authors.initials: A
authors.lastname: Pham
authors.forename: Frank S
authors.initials: FS
authors.lastname: Werblin
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D025602:Halorhodopsins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D010775:Photic Stimulation / Q000379:methods; D011817:Rabbits; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism
chemical_list: D017487:Ankyrins; D018691:Excitatory Amino Acid Antagonists; D025602:Halorhodopsins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C485184:enhanced green fluorescent protein; C033652:postsynaptic density proteins; D049452:Green Fluorescent Proteins; D012243:Rhodopsin