ins.Vardi

advertisement
Noga Vardi, Ph.D.
Research Associate Professor,
Department of Neuroscience
122B Anatomy/Chemistry Building/6058 (215) 898-4520 FAX: (215) 898-6228
email: noga@retina.anatomy.upenn.edu
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.
Download