This research application represents a broad investigation into the mechanisms of cell communication in the vertebrate retina. Our objectives are centered on three main issues. These include (1) the mechanisms in the inner retina which are subserved by the release of glutamate and the different types of glutamate receptors, both ionotropic and metabotropic, which interact to regulate the excitability of ganglion cells; (2) the identification and biophysical characterization of voltage-gated Ca2+ channels in ganglion cells with special emphasis on T-type Ca2+ channels, their pharmacological properties and cellular distribution in the dendrites and soma. We plan to evaluate how T-type Ca2+ channels contribute to nerve impulse generation and whether these ion channels play a role in amplifying synaptic currents which are generated on the dendrites. The third broad mission of this application is dedicated to a better understanding of dendritic physiology by recording from dendrites and isolated dendrosomes to further define the physiological properties of AMPA, NMDA and KA receptors. The methods used in this study will include electrophysiology, Ca2+ imaging and the use of photolysis to introduce chemical agents quickly and apply them locally at visually targeted dendritic regions. These experiments will be carried out in the amphibian retina and are designed to enhance our understanding about the mechanisms by which cells interact with one another and contribute to the excitability of retinal ganglion cells. The health-related implications of this research are extensive and relate to the mechanisms which control cellular functions of ganglion cells and how these mechanisms may help or hinder the stability of these cells when confronted with the stress of several different disease states, including glaucoma and diabetic retinopathy.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003014-26
Application #
6635558
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Hunter, Chyren
Project Start
1978-09-30
Project End
2005-08-31
Budget Start
2003-04-01
Budget End
2005-08-31
Support Year
26
Fiscal Year
2003
Total Cost
$316,350
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Neurosciences
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Gustafson, Eric G; Stevens, Eric S; Miller, Robert F (2015) Dynamic regulation of D-serine release in the vertebrate retina. J Physiol 593:843-56
Romero, Gabriel E; Lockridge, Amber D; Morgans, Catherine W et al. (2014) The postnatal development of D-serine in the retinas of two mouse strains, including a mutant mouse with a deficiency in D-amino acid oxidase and a serine racemase knockout mouse. ACS Chem Neurosci 5:848-54
Gustafson, Eric C; Morgans, Catherine W; Tekmen, Merve et al. (2013) Retinal NMDA receptor function and expression are altered in a mouse lacking D-amino acid oxidase. J Neurophysiol 110:2718-26
Sullivan, Steve J; Miller, Robert F (2012) AMPA receptor-dependent, light-evoked D-serine release acts on retinal ganglion cell NMDA receptors. J Neurophysiol 108:1044-51
Stevens, Eric R; Gustafson, Eric C; Miller, Robert F (2010) Glycine transport accounts for the differential role of glycine vs. D-serine at NMDA receptor coagonist sites in the salamander retina. Eur J Neurosci 31:808-16
Stevens, Eric R; Gustafson, Eric C; Sullivan, Steven J et al. (2010) Light-evoked NMDA receptor-mediated currents are reduced by blocking D-serine synthesis in the salamander retina. Neuroreport 21:239-44
Sullivan, Steve J; Miller, Robert F (2010) AMPA receptor mediated D-serine release from retinal glial cells. J Neurochem 115:1681-9
Reed, Brian T; Sullivan, Steven J; Tsai, Guochuan et al. (2009) The glycine transporter GlyT1 controls N-methyl-D-aspartic acid receptor coagonist occupancy in the mouse retina. Eur J Neurosci 30:2308-17
Perge, János A; Koch, Kristin; Miller, Robert et al. (2009) How the optic nerve allocates space, energy capacity, and information. J Neurosci 29:7917-28
Balasubramanian, Vijay; Sterling, Peter (2009) Receptive fields and functional architecture in the retina. J Physiol 587:2753-67

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