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.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Schools of Medicine
United States
Zip Code
Duvoisin, Robert M; Haley, Tammie L; Ren, Gaoying et al. (2017) Autoantibodies in Melanoma-Associated Retinopathy Recognize an Epitope Conserved Between TRPM1 and TRPM3. Invest Ophthalmol Vis Sci 58:2732-2738
Neuillé, Marion; Morgans, Catherine W; Cao, Yan et al. (2015) LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation. Eur J Neurosci 42:1966-75
Brown, R Lane; Xiong, Wei-Hong; Peters, James H et al. (2015) TRPM3 expression in mouse retina. PLoS One 10:e0117615
Reed, Brian T; Morgans, Catherine W; Duvoisin, Robert M (2013) Differential modulation of retinal ganglion cell light responses by orthosteric and allosteric metabotropic glutamate receptor 8 compounds. Neuropharmacology 67:88-94
Fendt, M; Bürki, H; Imobersteg, S et al. (2010) The effect of mGlu8 deficiency in animal models of psychiatric diseases. Genes Brain Behav 9:33-44
Jeffrey, Brett G; Morgans, Catherine W; Puthussery, Theresa et al. (2010) R9AP stabilizes RGS11-G beta5 and accelerates the early light response of ON-bipolar cells. Vis Neurosci 27:9-17
Zhang, Jianmei; Jeffrey, Brett G; Morgans, Catherine W et al. (2010) RGS7 and -11 complexes accelerate the ON-bipolar cell light response. Invest Ophthalmol Vis Sci 51:1121-9
Quraishi, S; Reed, B T; Duvoisin, R M et al. (2010) Selective activation of mGluR8 receptors modulates retinal ganglion cell light responses. Neuroscience 166:935-41
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

Showing the most recent 10 out of 36 publications