Under daylight conditions, vision depends on cone photoreceptors and the cone-driven retinal circuitry. Cone photoreceptors are susceptible to damage or destruction during diseases of both childhood (e.g., retinitis pigmentosa) and in the elderly (e.g., macular degeneration). An appreciation of the abnormalities in cone-mediated vision caused by these diseases depends upon our understanding of the function of cone circuits in the normal retina. Most common laboratory mammals (e.g., rat and rabbit) have rod-dominant retinas and are less-suitable for investigations of the circuitry underlying cone-mediated vision. As an alternative, we have pioneered the use of the ground squirrel retina, in which up to 95% of the photoreceptors are cones, and in which the postsynaptic bipolar cells are plentiful and easy to access for detailed electrophysiological measurements. A flash of light generates an """"""""analog"""""""" signal in cone photoreceptors that is graded with intensity and relatively sustained in duration. The signals in cone photoreceptors are then divided into two functional pathways at the cone to bipolar cell synapse: On-center and Off-center. We have shown, both in published work and in the Preliminary Results, that On and Off bipolar cells each can be further subdivided according to the temporal characteristics of their signals. Thus, of the ~4 anatomically distinct types of ground squirrel On bipolar cells, only one (the b5) can signal at light-on with an all-or-nothing Na+ action potential. Similarly, 1 of the ~4 types of Off bipolar cells (the b2) has fast AMPA receptors and can produce a rebound depolarization at light-off. Given their transient light responses, our goal is to test whether the b5 and b2 cells drive classes of retinal ganglion cells that produce transient responses at either the onset or offset of a step of light. Specifically, we will determine a) whether b5 and b2 cells costratify and make anatomical contacts with On and Off transient cells in the inner plexiform layer;b) whether b5 and b2 cells provide a transient synaptic input to the transient ganglion cells;and, c) and whether b5 and b2 cells cause the transient spike responses in On and Off transient ganglion cells.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY018204-04
Application #
7809479
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
2007-05-07
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
4
Fiscal Year
2010
Total Cost
$336,353
Indirect Cost
Name
Northwestern University at Chicago
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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