This project addresses a basic research priority of the NEI, which is to understand how retinal networks process visual images. The mammalian retina contains about 20 different types of retinal ganglion cell each having characteristic receptive field properties. Most ganglion cell types are image- forming in that they comprise an array of essentially identical neurons that completely sample the visual field. Our approach has been to target specific, anatomically and physiologically identified ganglion cells, and perform quantitative analyses of the light-evoked inputs in order to gain insights into the connectivity and neural pathways that mediate physiological responses. In this proposal we will address three aims.
Aim 1 proposes to test the hypothesis that selective expression of AMPA and kainate receptors in the outer plexiform layer contribute to temporal tuning in the ganglion cells.
Aim 2 proposes to examine the role of NMDA receptors in generating the receptive field properties of direction-selective ganglion cells, and ON brisk-sustained ganglion cells. We will use subunit-specific antagonists to probe differences in NMDA receptor function in the ON and OFF pathways.
Aim 3, in collaboration with Robert Smith at University of Pennsylvania, will use realistic computational models to predict the synaptic conductances, and estimate the magnitude of voltage-clamp errors in the ganglion cell recordings.

Public Health Relevance

The goal of this research is to understand how specific types of nerve cells in the retina transmit information about the visual scene to the brain. This information will advance our understanding of the neurobiological function of the healthy retina. The knowledge gained will help us to understand pathology in the diseased eye thus contribute to the development of therapies for human eye disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014888-11
Application #
8655865
Study Section
Biology and Diseases of the Posterior Eye (BDPE)
Program Officer
Greenwell, Thomas
Project Start
2003-07-01
Project End
2016-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
11
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Portland
State
OR
Country
United States
Zip Code
97239
Stincic, Todd L; Keeley, Patrick W; Reese, Benjamin E et al. (2018) Bistratified starburst amacrine cells in Sox2 conditional knockout mouse retina display ON and OFF responses. J Neurophysiol 120:2121-2129
Venkataramani, Sowmya; Taylor, W Rowland (2016) Synaptic Mechanisms Generating Orientation Selectivity in the ON Pathway of the Rabbit Retina. J Neurosci 36:3336-49
Taxidis, Jiannis; Anastassiou, Costas A; Diba, Kamran et al. (2015) Local Field Potentials Encode Place Cell Ensemble Activation during Hippocampal Sharp Wave Ripples. Neuron 87:590-604
Murphy-Baum, Benjamin L; Taylor, W Rowland (2015) The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal Amacrine Cell of the Rabbit Retina. J Neurosci 35:13336-50
Balakrishnan, Veeramuthu; Puthussery, Theresa; Kim, Mean-Hwan et al. (2015) Synaptic Vesicle Exocytosis at the Dendritic Lobules of an Inhibitory Interneuron in the Mammalian Retina. Neuron 87:563-75
Puthussery, Theresa; Percival, Kumiko A; Venkataramani, Sowmya et al. (2014) Kainate receptors mediate synaptic input to transient and sustained OFF visual pathways in primate retina. J Neurosci 34:7611-21
Venkataramani, Sowmya; Van Wyk, Michiel; Buldyrev, Ilya et al. (2014) Distinct roles for inhibition in spatial and temporal tuning of local edge detectors in the rabbit retina. PLoS One 9:e88560
Puthussery, Theresa; Venkataramani, Sowmya; Gayet-Primo, Jacqueline et al. (2013) NaV1.1 channels in axon initial segments of bipolar cells augment input to magnocellular visual pathways in the primate retina. J Neurosci 33:16045-59
Buldyrev, Ilya; Taylor, W Rowland (2013) Inhibitory mechanisms that generate centre and surround properties in ON and OFF brisk-sustained ganglion cells in the rabbit retina. J Physiol 591:303-25
Buldyrev, Ilya; Puthussery, Theresa; Taylor, W Rowland (2012) Synaptic pathways that shape the excitatory drive in an OFF retinal ganglion cell. J Neurophysiol 107:1795-807

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