This project proposes to study mechanisms of synaptic processing within specific ganglion cell types in the mammalian retina, both by direct neurophysiological recording and through the use of realistic computer models. Our visual system functions under a wide range of light conditions from night to day, and the retina adapts to prevent saturation, so that the output is largely invariant to changes in the illumination level. The synaptic mechanisms that accomplish adaptation and signal transmission introduce noise, which, coupled with the limited dynamic range of neurons, reduces the fidelity of the visual signal. To cope with this problem, the retina segments the visual world using different types of ganglion cells that each code specific visual features with high fidelity. This project focuses on a specific type of retinal ganglion cell that signals directional motion, called the direction-selective ganglion cell (DSGC). Using a live in-vitro isolated rabbit retina, we will record responses of neurons to light stimuli, and construct computational models of the responses to determine the biophysical mechanisms present. The study comprises three sections.
Aim 1 examines the function of the starburst amacrine cell (SBAC), essential for generating the direction selective signal for the DSGC.
This aim tests several hypotheses relating to specific biophysical mechanisms intrinsic to the cell, such as voltage-gated channels, that generate its directional output. A realistic computer model of the SBAC will help to determine which mechanisms are present.
Aim 2 tests the hypothesis that inhibition between adjacent cells within the network of SBACs is crucial for amplifying directional signals. The experimental results will be used to develop and test a computational model, derived from the results of Aim 1 that contains several SBACs with their network interactions.
Aim 3 examines noise and precision in the spiking output of the direction-selective ganglion cell, and will account for its spiking properties using a computational model based on physiological results from all three Aims. The final model will represent a detailed and essentially complete representation of directional signaling in the mammalian retina. Overall, the proposed research will improve our understanding of the complex circuitry of the adult retina;the knowledge gained will inform continuing efforts to develop treatments and visual prosthetic devices that restore vision loss from a range of eye diseases.

Public Health Relevance

The overall goal of this research project is to understand how specific nerve cells in the eye, the retinal ganglion cells, detect motion in our environment and relay that information to the brain. Improving our understanding of the healthy eye will inform and facilitate the continued development of novel therapeutic treatments for human eye disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY022070-02
Application #
8383102
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
2011-12-01
Project End
2015-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
2
Fiscal Year
2013
Total Cost
$372,875
Indirect Cost
$64,125
Name
Oregon Health and Science University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Trenholm, Stuart; McLaughlin, Amanda J; Schwab, David J et al. (2014) Nonlinear dendritic integration of electrical and chemical synaptic inputs drives fine-scale correlations. Nat Neurosci 17:1759-66