The main emphasis of the proposed research is to investigate the cellular and synaptic mechanisms underlying the processes of light and dark adaptation. The major tenet is that the hard wiring anatomically defines the physical synapses, but synaptic efficacy is modified by neuromodulators, such as dopamine, to accommodate the shift from rod- to cone-vision during dark and light adaptation. Studies are proposed to examine the dependency of light, voltage, Ca2+ and dopamine (D2 receptors) on glutamate release by photoreceptors in a """"""""reduced"""""""" retina preparation consisting of mostly photoreceptors, and by photoreceptor-derived synaptosomes. The effects of dopamine (D2) ligands on rod-cone coupling, as well as rod photovoltage and its flicker response will be examined with intracellular recordings and dye-coupling experiments. In addition, the kinetics of horizontal cell responses and coupling in the horizontal cell network will be studied during light/dark adaptation and during pharmacological manipulations. Recordings from isolated horizontal cells will be used to examine the modulatory effects of amino acid neurotransmitters on time- and voltage-dependent channels, and to assess the contribution each channel makes to sinusoidal modulation of the horizontal cell voltage within the physiological range. The role horizontal cells play in center-surround organization of ganglion cells and the variation of the surround strength as a consequence of light and dark adaptation will also be studied by passing current into horizontal cells while recording extracellular ganglion cell activity.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003570-19
Application #
2684477
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1980-04-01
Project End
2001-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
19
Fiscal Year
1998
Total Cost
Indirect Cost
Name
New York University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10016
Heidelberger, Ruth; Thoreson, Wallace B; Witkovsky, Paul (2005) Synaptic transmission at retinal ribbon synapses. Prog Retin Eye Res 24:682-720
Witkovsky, Paul; Arango-Gonzalez, Blanca; Haycock, John W et al. (2005) Rat retinal dopaminergic neurons: differential maturation of somatodendritic and axonal compartments. J Comp Neurol 481:352-62
Vigh, Jozsef; Witkovsky, Paul (2004) Neurotransmitter actions on transient amacrine and ganglion cells of the turtle retina. Vis Neurosci 21:1-11
Witkovsky, Paul (2004) Dopamine and retinal function. Doc Ophthalmol 108:17-40
Witkovsky, Paul; Veisenberger, Eleonora; Haycock, John W et al. (2004) Activity-dependent phosphorylation of tyrosine hydroxylase in dopaminergic neurons of the rat retina. J Neurosci 24:4242-9
Witkovsky, Paul; Veisenberger, Eleonora; LeSauter, Joseph et al. (2003) Cellular location and circadian rhythm of expression of the biological clock gene Period 1 in the mouse retina. J Neurosci 23:7670-6
Akopian, Abram; Witkovsky, Paul (2002) Calcium and retinal function. Mol Neurobiol 25:113-32
Gabriel, Robert; de Souza, Sunita; Ziff, Edward B et al. (2002) Association of the AMPA receptor-related postsynaptic density proteins GRIP and ABP with subsets of glutamate-sensitive neurons in the rat retina. J Comp Neurol 449:129-40
Thoreson, Wallace B; Stella Jr, Salvatore L; Bryson, Eric I et al. (2002) D2-like dopamine receptors promote interactions between calcium and chloride channels that diminish rod synaptic transfer in the salamander retina. Vis Neurosci 19:235-47
Witkovsky, P; Thoreson, W; Tranchina, D (2001) Transmission at the photoreceptor synapse. Prog Brain Res 131:145-59

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