The long-term objective is to understand the structure and function of the primate parallel visual pathways that originate at the first synapse in the retina, where signals from photoreceptors are transmitted to bipolar and horizontal cells. The major goals are to determine the structure of the trichromatic cone mosaic, the physiology of the cone photoreceptors, and how signals are transmitted from each cone type to a diverse array of morphologically distinct bipolar and horizontal cell types. New methods of photopigment imaging, intracellular physiology and electron microscopy will be applied to an in vitro preparation of the macaque monkey retina. The four specific aims are: (1) to determine the spatial distribution and synaptic connections of the long (L) and middle (M) wavelength-sensitive cone types using a new method of reflection densitometry and electron microscopy: the hypothesis that the L and M cone types form non-randomly distributed submosaics and are linked to synaptically distinct bipolar cells pathways to the inner retina will be tested; (2) to determine the spatial structure of the cone receptive field, testing the hypothesis that cones have a center-surround receptive field organization and that the surround confers color opponency to the light response; (3) to determine the cone connections and receptive field structure of morphologically identified cone bipolar cell types: the hypothesis that distinct cone bipolar cell types transmit both luminance and chromatically opponent signals in parallel to the inner retina will be tested; and (4) to determine the functional connections among horizontal, bipolar and cone cell types. The hypothesis that horizontal cells make feedback connections to cones and feedforward connections to bipolar cells, thereby generating the inhibitory receptive field surround in both cones and bipolar cells, will be tested. The resulting data will permit an exploration of the functional microcircuitry of the outer retina and its role in color vision, temporal sensitivity and light adaptation. Because the outer retina of the macaque is so similar to that of the human, it will provide the best and most detailed structure-function model of the human outer retina. The results are expected to contribute to a new foundation for understanding the cellular origins of human retinal disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009625-10
Application #
6384347
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Mariani, Andrew P
Project Start
1992-05-01
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
10
Fiscal Year
2001
Total Cost
$342,970
Indirect Cost
Name
University of Washington
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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
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
Smith, Vivianne C; Pokorny, Joel; Lee, Barry B et al. (2008) Sequential processing in vision: The interaction of sensitivity regulation and temporal dynamics. Vision Res 48:2649-56
Gamlin, Paul D R; McDougal, David H; Pokorny, Joel et al. (2007) Human and macaque pupil responses driven by melanopsin-containing retinal ganglion cells. Vision Res 47:946-54
Packer, Orin S; Dacey, Dennis M (2005) Synergistic center-surround receptive field model of monkey H1 horizontal cells. J Vis 5:1038-54
McMahon, Matthew J; Packer, Orin S; Dacey, Dennis M (2004) The classical receptive field surround of primate parasol ganglion cells is mediated primarily by a non-GABAergic pathway. J Neurosci 24:3736-45
Diller, Lisa; Packer, Orin S; Verweij, Jan et al. (2004) L and M cone contributions to the midget and parasol ganglion cell receptive fields of macaque monkey retina. J Neurosci 24:1079-88
Dacey, Dennis M; Packer, Orin S (2003) Colour coding in the primate retina: diverse cell types and cone-specific circuitry. Curr Opin Neurobiol 13:421-7

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