Studies in several species have shown that a number of visual phenomena are regulated by circadian mechanisms. For example, synaptic ribbons in photoreceptor terminals in larval zebrafish undergo dramatic diurnal alterations. The ribbons are very prominent during day, but are almost completely absent at night. The implications of this circadian driven process on visual function are not well understood. The proposed experiments are aimed at investigating how plasticity of synaptic ribbons in the eye relates to visual responsiveness in larval zebrafish. Preliminary studies show that larval fish at 5 days of age have normal electroretinograms (ERGs) during the day, but fail to respond to illumination at night. Two behavioral tests, the optokinetic response (OKR) and the visual-motor response (VMR), indicate that fluctuations in visual responsiveness in the day and night are not only profound in larval zebrafish, but that vision may be completely lost at night.
In Specific Aim 1, I will determine how the changes in ERG and visual behavioral sensitivity alter as a function of time of day and light exposure in larval zebrafish. Single-unit and ERG recordings will be used to determine the changes in the functional properties of retinal cells in the inner and outer retina. The OKR and the VMR tests will be used to determine how time of day and light exposure affects visual responsiveness and behavior of zebrafish.
In Specific Aim 2, I will characterize and quantitate changes in ribbon structure in the retina under physiological conditions as well as under various light and dark conditions. The structural changes of synaptic ribbons will be studied by electron microscopy or immunohistochemistry using antibodies against synaptic ribbon proteins.

Public Health Relevance

Zebrafish have emerged as a powerful model system to study processes underlying visual system development and differentiation. Ultrastructural analysis on larval zebrafish have shown that synaptic ribbons in photoreceptor terminals undergo structural changes over the course of the day and that this process is circadian driven. The implications of this circadian driven process on visual function are not well understood. Further analysis of synaptic ribbons may help identify its role in normal vision and in disease states.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32EY018044-01A2
Application #
7608775
Study Section
Special Emphasis Panel (ZRG1-F02B-Y (20))
Program Officer
Greenwell, Thomas
Project Start
2008-12-01
Project End
2010-11-30
Budget Start
2008-12-01
Budget End
2009-11-30
Support Year
1
Fiscal Year
2009
Total Cost
$53,354
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Hensley, Monica R; Emran, Farida; Bonilla, Sylvia et al. (2011) Cellular expression of Smarca4 (Brg1)-regulated genes in zebrafish retinas. BMC Dev Biol 11:45
Stujenske, Joseph M; Dowling, John E; Emran, Farida (2011) The bugeye mutant zebrafish exhibits visual deficits that arise with the onset of an enlarged eye phenotype. Invest Ophthalmol Vis Sci 52:4200-7
Emran, Farida; Rihel, Jason; Adolph, Alan R et al. (2010) Zebrafish larvae lose vision at night. Proc Natl Acad Sci U S A 107:6034-9
Emran, Farida; Rihel, Jason; Dowling, John E (2008) A behavioral assay to measure responsiveness of zebrafish to changes in light intensities. J Vis Exp :