Retinal dopamine appears involved in light adaptation in all vertebrates, including human. Dopamine depletion in goldfish retina causes a chronic 100-fold increase in light sensitivity. When the retina is reinnervated with a sparse plexus of dopamine processes, synaptic contact is reestablished with horizontal cells but not with ON bipolar cells. It is hypothesized that synaptic contact is necessary for dopamine control of bipolar cells that are responsible for a normal transition from light-to dark-adaptation. It is predicted that horizontal cell responses to dopamine are independent of direct dopamine innervation, whereas bipolar cells depend upon direct dopamine input. These predictions will be tested in electrophysiological and immunocytochemical studies in control, dopamine-depleted (depleted by intraocular injection of 6-hydroxydopamine) and partially reinnervated retinas.
Specific aim 1 is to determine electrophysiological properties (voltage- and ligand-gated) of bipolar cells (using whole-dell recording) and horizontal cells (by intracellular recording) in the retinal slice. Initial focus will be on K+ currents, effects of ascorbate, dopamine D1 ligands and GABA.
Specific aim 2 proposes to use immunocytochemistry to determine the content and distribution of transmitter- and channel-specific markers by light and electron microscopy. Initial focus will be on K+ channels, glutamate-, dopamine D1- and GABAc-receptors. In addition, it is proposed to use antibodies against agmatine, a selective permeant of cation channels gated by AMPA/NMDA receptors, to determine the relative activity of horizontal cells and OFF bipolar cells.
Specific aim 3 is to test the hypothesis that color opponency of bipolar cells is due to direct input from photoreceptors, rather than feedback from horizontal cells, by determining the chromatically-induced intracellular responses of bipolar and horizontal cells in the retinal slice. This project will provide data regarding: (1) the cellular basis of the acute, chronic and recovery phase of dopamine depletion on luminosity coding, (2) elucidation of a dual mechanism for the control of retinal processes by dopamine, i.e., volume and wiring transmission, and (3) the relative contribution of horizontal cells and bipolar cells to luminosity and color coding.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY001682-26
Application #
6384274
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Hunter, Chyren
Project Start
1979-05-01
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
26
Fiscal Year
2001
Total Cost
$390,828
Indirect Cost
Name
State University New York Stony Brook
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Klooster, Jan; Yazulla, Stephen; Kamermans, Maarten (2009) Ultrastructural analysis of the glutamatergic system in the outer plexiform layer of zebrafish retina. J Chem Neuroanat 37:254-65
Yazulla, Stephen (2008) Endocannabinoids in the retina: from marijuana to neuroprotection. Prog Retin Eye Res 27:501-26
Zimov, Sarah; Yazulla, Stephen (2008) Novel processes invaginate the pre-synaptic terminal of retinal bipolar cells. Cell Tissue Res 333:1-16
Zimov, Sarah; Yazulla, Stephen (2007) Vanilloid receptor 1 (TRPV1/VR1) co-localizes with fatty acid amide hydrolase (FAAH) in retinal amacrine cells. Vis Neurosci 24:581-91
Fan, Shih-Fang; Yazulla, Stephen (2007) Retrograde endocannabinoid inhibition of goldfish retinal cones is mediated by 2-arachidonoyl glycerol. Vis Neurosci 24:257-67
Hull, Court; Studholme, Keith; Yazulla, Stephen et al. (2006) Diurnal changes in exocytosis and the number of synaptic ribbons at active zones of an ON-type bipolar cell terminal. J Neurophysiol 96:2025-33
Struik, Mieke L; Yazulla, Stephen; Kamermans, Maarten (2006) Cannabinoid agonist WIN 55212-2 speeds up the cone response to light offset in goldfish retina. Vis Neurosci 23:285-93
Glaser, Sherrye T; Deutsch, Dale G; Studholme, Keith M et al. (2005) Endocannabinoids in the intact retina: 3 H-anandamide uptake, fatty acid amide hydrolase immunoreactivity and hydrolysis of anandamide. Vis Neurosci 22:693-705
Fan, Shih-Fang; Yazulla, Stephen (2005) Reciprocal inhibition of voltage-gated potassium currents (I K(V)) by activation of cannabinoid CB1 and dopamine D1 receptors in ON bipolar cells of goldfish retina. Vis Neurosci 22:55-63
Fan, Shih-Fang; Yazulla, Stephen (2004) Inhibitory interaction of cannabinoid CB1 receptor and dopamine D2 receptor agonists on voltage-gated currents of goldfish cones. Vis Neurosci 21:69-77

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