The goal of the proposal is to exploit advanced optical recording methods to study the basic properties of retinal dendrites and the role they play in the collection, integration and processing of visual information. Dendrites are the most dominant feature of a retinal neuron; they cover more surface area and are functional more complex than any other neuronal component, yet they are the least understood. They are too small for routine electrical recording, but it is possible to record from dendrites optically using two-photon laser scanning fluorescent microscopy to excite a Ca2+ -dependent fluorophore and measure changes in the fluorescence signal in response to visual stimulation. The investigator is a pioneer in the use of this method and has demonstrated its unique ability to monitor signals from dendritic compartments too small to be recorded form in any other way. In this research optical recording will be used to study the mechanisms responsible for the generation of light-evoked dendritic Ca2+ signals and their spatio-temporal spread through the dendritic arbor. This includes determining the relationship between the properties of the Ca2+ signal and visual stimulus that evoked it under dark and light adapted conditions. The retina is an image processor that is made up of neurons whose function as computational units depends on their dendrites. Hence in order to replace an eye lost to disease or trauma with a prosthetic devise it is necessary to first know how the neurons work and this requires knowing how their dendrites work. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY002048-28A1
Application #
7382700
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
1977-09-01
Project End
2012-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
28
Fiscal Year
2008
Total Cost
$342,135
Indirect Cost
Name
University of Washington
Department
Psychiatry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Newkirk, G S; Hoon, M; Wong, R O et al. (2015) Response Properties of a Newly Identified Tristratified Narrow Field Amacrine Cell in the Mouse Retina. PLoS One 10:e0137702
Margolis, David J; Gartland, Andrew J; Singer, Joshua H et al. (2014) Network oscillations drive correlated spiking of ON and OFF ganglion cells in the rd1 mouse model of retinal degeneration. PLoS One 9:e86253
Newkirk, G S; Hoon, M; Wong, R O et al. (2013) Inhibitory inputs tune the light response properties of dopaminergic amacrine cells in mouse retina. J Neurophysiol 110:536-52
Theer, Patrick; Denk, Winfried; Sheves, Mordechai et al. (2011) Second-harmonic generation imaging of membrane potential with retinal analogues. Biophys J 100:232-42
Gartland, Andrew J; Detwiler, Peter B (2011) Correlated variations in the parameters that regulate dendritic calcium signaling in mouse retinal ganglion cells. J Neurosci 31:18353-63
Margolis, David J; Gartland, Andrew J; Euler, Thomas et al. (2010) Dendritic calcium signaling in ON and OFF mouse retinal ganglion cells. J Neurosci 30:7127-38
Crook, Joanna D; Davenport, Christopher M; Peterson, Beth B et al. (2009) Parallel ON and OFF cone bipolar inputs establish spatially coextensive receptive field structure of blue-yellow ganglion cells in primate retina. J Neurosci 29:8372-87
Euler, Thomas; Hausselt, Susanne E; Margolis, David J et al. (2009) Eyecup scope--optical recordings of light stimulus-evoked fluorescence signals in the retina. Pflugers Arch 457:1393-414
Margolis, David J; Newkirk, Gregory; Euler, Thomas et al. (2008) Functional stability of retinal ganglion cells after degeneration-induced changes in synaptic input. J Neurosci 28:6526-36
Davenport, Christopher M; Detwiler, Peter B; Dacey, Dennis M (2008) Effects of pH buffering on horizontal and ganglion cell light responses in primate retina: evidence for the proton hypothesis of surround formation. J Neurosci 28:456-64

Showing the most recent 10 out of 37 publications