Glutamate is the major excitatory neurotransmitter in the vertebrate CNS. In the retina it is the neurotransmitter used along the feed-forward pathway from photoreceptors, to bipolar cells, to ganglion cells. Glutamatergic transmission is mediated by glutamate receptors, of which there are two broad classes: lonotropic glutamate receptors are ligand-gated ion channels. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors and their function is mediated by second messenger pathways. The objective of this project is to determine the distribution and function of group-Ill mGluRs in the inner plexiform layer of the retina. Group-Ill mGluRs are selectively activated by L-2-amino-4-phosphonobutyric acid (APB, also abbreviated L-AP4) and consist of mGluR4, -R6, -R7, and -R8. mGluR6 is present in ON bipolar cell dendrites and mediates the depolarizing response of these cells to light, generating the ON visual pathway. While the other group-Ill mGluRs are known to be widely expressed in the brain, indicating that they may be involved in a number of pathologies, their precise distribution and function in the retina is poorly characterized. Group-Ill mGluRs are currently tested as targets for therapeutic drugs, and it is important to know what effects on vision these drugs may have. Moreover, because the expression of group-Ill mGluRs is not restricted to the retina, a better understanding of their function in the retina will have broader significance for our understanding of normal and pathological brain function. In the retina, we hypothesize that group-Ill mGluRs are present in bipolar cell terminals and in amacrine cells where they regulate neurotransmitter release.
The specific aims of this project are 1) to localize immunohistochemically group-Ill mGluRs in the rabbit retina;2) to determine the effects of mGluR4, -R7 and -R8 stimulation on the light responses of starburst amacrine and ganglion cells;and 3) to determine the role of group-Ill mGluRs in the generation of photopic ERG oscillatory potentials.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009534-16
Application #
7738471
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
1992-04-01
Project End
2012-11-30
Budget Start
2009-12-01
Budget End
2012-11-30
Support Year
16
Fiscal Year
2010
Total Cost
$344,641
Indirect Cost
Name
Oregon Health and Science University
Department
Physiology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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Morgans, Catherine W; Zhang, Jianmei; Jeffrey, Brett G et al. (2009) TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells. Proc Natl Acad Sci U S A 106:19174-8
Puthussery, Theresa; Gayet-Primo, Jacqueline; Pandey, Shilpi et al. (2009) Differential loss and preservation of glutamate receptor function in bipolar cells in the rd10 mouse model of retinitis pigmentosa. Eur J Neurosci 29:1533-42

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