The mammalian retina contains at least 15-20 types of retinal ganglion cells each tuned to respond best to different and sometimes complex features in a visual scene. Together, these diverse ganglion cell responses provide us with all of the information that we use to navigate in the visual world. Each type of retinal ganglion cell monitors a patch on the retinal surface, its receptive field, by collecting inputs from presynaptic bipolar and amacrine cells of which there are more than 12 and 30 types, respectively. While the general patterns of amacrine and bipolar cell connectivity that contribute to he ganglion cell light response are known, the daunting complexity of the IPL has impeded our understanding of the specific connections that underlie the tuning properties that distinguish the ganglion cell types. We have developed a toolbox of optogenetic and virally-based techniques that will enable us to trace and functionally characterize the connections between bipolar, amacrine, and ganglion cells in both the rod dominant mouse and cone dominant ground squirrel retinas. In three specific aims, our goals are to: 1) test the hypothesis that ganglio cells obtain different temporal light responses, in part, by summing the excitatory inputs of bipolar cells with different temporal responses. 2) test the hypothesis that ganglion cells obtain direct input from different types of amacrine cells with different temporal properties and, 3) determine the functional connections and the role in vision of a specific amacrine cell type that expresses cre recombinase under the control of the corticotropin releasing hormone (CRH) promoter. Our work will define the wiring and functions of specific inner retinal circuits i health, and provide the background for understanding circuit changes that are known to occur following photoreceptor degeneration, whether from genetic or age-onset disease.

Public Health Relevance

Nerve signals originating in the rod and cone photoreceptors are processed by circuits in the inner retina to give rise to separate visual streams that carry information about, for example, object motion and color. These circuits become disrupted following photoreceptor degeneration in both genetic and age-onset disease. Our work will help to define the wiring and functions of these circuits in the healthy retina, and will provide the background for understanding circuit changes in the diseased state.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY018204-06
Application #
8460361
Study Section
Special Emphasis Panel (ZRG1-CB-G (02))
Program Officer
Greenwell, Thomas
Project Start
2007-05-07
Project End
2017-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
6
Fiscal Year
2013
Total Cost
$529,118
Indirect Cost
$179,592
Name
Northwestern University at Chicago
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Zhu, Yongling; Xu, Jian; Hauswirth, William W et al. (2014) Genetically targeted binary labeling of retinal neurons. J Neurosci 34:7845-61
Saszik, Shannon; DeVries, Steven H (2012) A mammalian retinal bipolar cell uses both graded changes in membrane voltage and all-or-nothing Na+ spikes to encode light. J Neurosci 32:297-307