Novel mechanisms and roles of inhibition in retinal light adaptation
Abstract
The overall goal of the proposed research is to test the novel hypothesis that dopamine-mediated inhibition of OFF-bipolar cells is responsible for increasing the spatial resolution of OFF-ganglion cells which would underlie the increase in sensitivity of OFF ganglion cells to small spots of light during conditions of light adaptation. Tasking to achieve the objective of this proposal will include a novel combination of direct real-time measurement of dopamine levels, genetically modified mouse lines, pharmacology and optogenetic activation of inhibitory amacrine cells in the retina. Together, these tools will allow measurement of the timing of dopamine release and the mechanisms and roles of OFF bipolar cell inhibition light adaptation in OFF ganglion cell spatial resolution and will be addressed in two major aims. In Aim 1 proposer will test the hypothesis that dopamine release and light adaptation narrow the spatial extent of OFF bipolar cell inhibition upstream of bipolar cells by (1) uncoupling gap junctions between amacrine cells that create extended spatial networks or (2) by increasing inhibitory connections between amacrine cells that limit the spatial extent of inhibition. Proposer plans to determine what mechanisms underlie the decrease in spatial extent of inhibition of OFF-bipolar cells with light adaptation and how dopamine release changes in real-time with light adaptation. Mouse models will include specific gap junction knockouts or optogenetically-activated amacrine cells. In Aim 2 proposer will determine if light adaptation of OFF bipolar cell (through the mechanisms tested in Aim 1) is responsible for the increased response of ganglion cells to small spots of light with light adaptation. determine if the light adaptation narrowing of OFF-bipolar cell inhibition changes the spatial receptive field of OFF-ganglion cells. hypothesize that these changes will increase the spatial resolution of OFF-ganglion cells by decreasing the amount of wide-field inhibition to OFF-bipolar cells. Techniques from Aim 1 will be employed here in addition to computational modeling which will help abstract retinal processing and determine how these biophysical mechanisms affect OFF-ganglion cell signaling.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 12, 2017
- Source ID
- W911NF1510613
Entities
People
- Erika D. Eggers
Organizations
- Army Contracting Command
- United States Army
- University of Arizona