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.
| 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 |
| Guimarães-Souza, E M; Perche, O; Morgans, C W et al. (2016) Fragile X Mental Retardation Protein expression in the retina is regulated by light. Exp Eye Res 146:72-82 |
| Brown, R Lane; Xiong, Wei-Hong; Peters, James H et al. (2015) TRPM3 expression in mouse retina. PLoS One 10:e0117615 |
| 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 |
| 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 |
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