The goal of the laboratory is to better understand the molecular mechanisms of neural processing in the retina. It is known that the segregation of light stimuli into ON and OFF pathways is done at the level of the bipolar cells. Since it is thought that photoreceptor cells release glutamate as a neurotransmitter, the functional difference between ON and OFF bipolar cells is proposed to be the result of their expressing distinct glutamate receptors. Specifically this proposal aims to explore the relationship between the expression of different glutamate receptors and the diversity of bipolar cells in the mouse retina. 1.Glutmate receptors in OFF bipolar cells. The diversity and distribution of glutamate receptor subunits will be examined in OFF bipolar cells by in situ hybridization and immunonohistochemical analyses of horizontal and vertical retinal sections and dissociated retinal cells. Glutamate receptor subunit expression in electrophysiologically identified individual OFF bipolar cells will be determined using the PCR technique. 2.Glutamate receptors in ON bipolar cells. The APB-type glutamate receptor, which is thought to mediate the sign inversion in ON bipolar cells, will be cloned. Antibodies will be raised against fragments of the APB receptor expressed in bacteria. The diversity and distribution of glutamate receptors will be examined in ON bipolar cells by in situ hybridization and immunohistochemical analyses of horizontal and vertical retinal sections and dissociated retinal cells. Glutamate receptor expression in electrophysiologically identified individual ON bipolar cells will be analyzed using the PCR technique. 3.Glutamate receptors during development. Studies have shown an early exrpession of neurotransmitter receptors in the developing brain, suggesting some role in the establishment of neural circuitry. The regulation of glutamate receptor expression in relation to the differentiation of bipolar cells will be analyzed using in situ hybridization and immunohistochemistry. The research proposed here will provide the basis with which to analyze the expression of glutamte receptors in mice with retinal degenerations and to assess the effects of receptor alterations during development and in the adult retina using transgenic mice.
| 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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