Noga Vardi, Ph.D. Research Associate Professor, Department of Neuroscience 122B Anatomy/Chemistry Building/6058 (215) 898-4520 FAX: (215) 898-6228 email: email@example.com More information on Noga's research: http://retina.anatomy.upenn.edu/%7Enoga/noga.html RESEARCH INTERESTS Retinal processing with focus on chemical architecture and principles of signal processing. RESEARCH TECHNIQUES Immunocytochemistry; dye injection; electron microscopy; molecular biology; yeast two hybrid systems; patch clamp from bipolar cells, and two electrode voltage clamp of oocytes. RESEARCH SUMMARY General Description: the retina can serve as an excellent model system for signal processing because the input (visual image) is well defined, the output (i.e. ganglion cell responses) has been thoroughly studied, and circuits of parallel pathways from photoreceptor to ganglion cells were described. Consequently, in retina one can address questions at all levels and integrate molecular and biochemical information with high percepts of vision. To reliably transfer the signal from photoreceptor to ganglion cells through these pathways under a large range of luminances the retina employs gain control and noise removal mechanisms. Gain is adjusted by GABAergic and glycinergic feedback circuits in the outer and inner plexiform layers. These circuits tune photoreceptor, bipolar and ganglion cells' responses by averaging and feeding back ambient light information. Noise in retina is reduced by convergence, thresholding mechanisms, feedback circuits, and gap junction modulation. Our goal is to investigate exactly how these mechanisms operate. We therefore study the anatomical and chemical details of the circuit design. Currently we are focusing on the second messenger cascade in ON bipolar cells. The ON bipolar cells express the metabotropic glutamate receptor mGluR6. We have recently found that mGluR6 activates the G-protein Go, and this eventually closes a nonspecific cation channel. Much effort is now devoted to identify the bipolar transduction channel. Tangent to this, we have recently discovered that mGluR6 is present in epithelial cells. This was surprising because mGluR6 was thought to be retina-specific. Using calcium and chloride imaging, we are now trying to investigate the broad function of mGluR6. KEY WORDS: MGluR6, glutamate; G-protein; calcium channel, GABA; feedback; cation chloride cotransporters; second messenger cascades; calcium imaging, chloride imaging. KEY REFERENCES Shoshan-Barmatz V, Orr I, Martin C, Vardi N. (2005) Novel ryanodine-binding properties in mammalian retina. Int J Biochem Cell Biol. 37:1681-95 Kao YH, Lassová L, Bar-Yehuda T, Edwards RH, Sterling P, Vardi N (2004) Evidence that certain retinal bipolar cells use both glutamate and GABA. J Comp Neurol 478:207-218. Norton AW, Hosier S, Terew JM, Li N, Dhingra A, Vardi N, Baehr W, Cote RH (2004) Evaluation of the 17 kDa prenyl binding protein as a regulatory protein for phototransduction in retinal photoreceptors. JBC 280:1248-56. Dhingra Anuradha, Eva Faurobert, Peter Sterling, Nathan Dascal, and Noga Vardi. (2004) RetRGS1 modulates the ON bipolar’s mGluR6 transduction cascade. J Neurosci 24: 5684-93. Dhingra A, Jiang M, Wang TL, Lyubarsky A, Savchenko A, Bar-Yehuda T, Sterling P, Birnbaumer L, and Vardi N. (2002) Ligh response of retinal ON bipolar cells requires a specific splice variant of Gao J. Neurosci. 22:4878-4884. Dhingra, A.; Lyubarsky, A.; Jiang, M.; Pugh, E.N. Jr.; Birnbaumer, L.; Sterling, P.; N. Vardi (2000) The light response of ON bipolar neurons requires Gao. J. Neurosci. 20(24):9053-9058. Vardi, N.; Zhang, L.-L.; Payne, J.A.; P. Sterling (2000) Evidence that different cation chloride cotransporters in retinal neurons allow opposite responses to GABA. J. Neurosci. 20(20):76577663. Vardi, N., Duvoisin R., Wu, G., and Sterling P. (2000) Localization of mGluR6 to dendrites of ON bipolar cells in primate retina. J. Comp. Neurol: 423. Wang, T.-L., Sterling, P. and Vardi, N. (1999) Localization of type I IP3 receptor in the outer segments of mammalian cones. J. of Neurosci. 19(11): 4221-4228. Vardi N., Morigiwa, K., Wang, T-L., Shi, Y-J., and Sterling P. (1998) Neurochemistry of the photoreceptor synaptic complex. Vision Research 38 (10): 1359-1369. Vardi, N. (1998) ON bipolar dendrites in mammalian retina express Go. J. Comp. Neurol. 385:43-52. Vardi, N. and Smith, R. G. (1996) The AII amacrine network: Coupling can increase correlated activity. Vision Res., 36: 3743-3757.