The long-range goal is to identify, in a non-human primate model, the structure and physiology of diverse retinal cell types, and to understand how retinal circuitry creates the parallel pathways of the visual system. The broad goal for the next project period is to characterize the morphology, physiology and central connections of newly identified color-, motion- and intrinsically photosensitive ganglion cell types. To accomplish these goals we will first apply a new method termed 'retrograde photodynamics' to the macaque retina to link physiology, anatomy and central connectivity of novel ganglion cell types. Second, we will apply a new method of optical imaging of light-evoked dendritic calcium signals to ganglion cell types in vitro to determine how L-, M- and S-cone inputs to specialized dendritic structures signal color. The proposed research has 4 specific aims: 1) To determine the visual response properties of novel LGN-projecting ganglion cell types. We will test the hypothesis that newly identified large mono- and bistratified cells code for color. 2) To determine the visual response properties of novel ganglion cell types that project to the superior colliculus. We will test hypothesis that the recursive monostratified and bistratified types are the origin ON- and ON-OFF-direction selective signals in primate. 3) To determine the anatomy, physiology and central connections of a unique population of melanopsin-containing, photoreceptive ganglion cells. 4) To determine the cone specificity of light-evoked calcium signals in the dendrites of color opponent ganglion cells. We will test the hypothesis that cone-type selective input to dendritic tree components of the large bistratified cells is the key mechanism for 'red-green' color opponency. Many aspects of macaque visual pathway organization are comparable to human; our results therefore will contribute to the best and most detailed structure-function model of the cell types of the human retina and visual pathways. Until now the majority of diverse primate ganglion cell types have been inaccessible to detailed physiological and anatomical analysis and their function and relevance to human disease and visual disorders has remained unexplored. The proposed projects will clarify the retinal origins and circuits for color-, irradiance- and motion-sensitive pathways that underlie many aspects of visual performance, the cellular basis for psychophysical measures of vision and mechanisms by which retinal disease affects human vision.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY006678-19A1
Application #
6823581
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Hunter, Chyren
Project Start
1986-02-01
Project End
2009-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
19
Fiscal Year
2004
Total Cost
$516,174
Indirect Cost
Name
University of Washington
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Wool, Lauren E; Crook, Joanna D; Troy, John B et al. (2018) Nonselective Wiring Accounts for Red-Green Opponency in Midget Ganglion Cells of the Primate Retina. J Neurosci 38:1520-1540
Liao, Hsi-Wen; Ren, Xiaozhi; Peterson, Beth B et al. (2016) Melanopsin-expressing ganglion cells on macaque and human retinas form two morphologically distinct populations. J Comp Neurol 524:2845-72
Hannibal, J; Kankipati, L; Strang, C E et al. (2014) Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey. J Comp Neurol 522:2231-48
Dacey, Dennis M; Crook, Joanna D; Packer, Orin S (2014) Distinct synaptic mechanisms create parallel S-ON and S-OFF color opponent pathways in the primate retina. Vis Neurosci 31:139-51
Joo, Hannah R; Peterson, Beth B; Dacey, Dennis M et al. (2013) Recurrent axon collaterals of intrinsically photosensitive retinal ganglion cells. Vis Neurosci 30:175-82
Schmidt, Tiffany M; Do, Michael Tri H; Dacey, Dennis et al. (2011) Melanopsin-positive intrinsically photosensitive retinal ganglion cells: from form to function. J Neurosci 31:16094-101
Joo, Hannah R; Peterson, Beth B; Haun, Toni J et al. (2011) Characterization of a novel large-field cone bipolar cell type in the primate retina: evidence for selective cone connections. Vis Neurosci 28:29-37
Crook, Joanna D; Manookin, Michael B; Packer, Orin S et al. (2011) Horizontal cell feedback without cone type-selective inhibition mediates ""red-green"" color opponency in midget ganglion cells of the primate retina. J Neurosci 31:1762-72
Packer, Orin S; Verweij, Jan; Li, Peter H et al. (2010) Blue-yellow opponency in primate S cone photoreceptors. J Neurosci 30:568-72
Crook, Joanna D; Davenport, Christopher M; Peterson, Beth B et al. (2009) Parallel ON and OFF cone bipolar inputs establish spatially coextensive receptive field structure of blue-yellow ganglion cells in primate retina. J Neurosci 29:8372-87

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