Rod vision in mammals is remarkably sensitive, allowing vision under conditions where few rods absorb photons. Additionally, rod vision extends over 8 orders of magnitude in light intensity above this threshold. The experiments described in this proposal are aimed at elucidating fundamental retinal mechanisms that allow both the discrimination of rod photoresponses from noise near visual threshold, and allow rod photoresponses to be transmitted to retinal ganglion cells through several parallel pathways over a wide range of light intensities. To accomplish these goals we propose to record light-evoked responses from rod photoreceptors and downstream retinal neurons (bipolar cells, amacrine cells, and ganglion cells) of wild-type and several transgenic mouse strains.
We aim to answer several fundamental questions about how rod photoresponses are processed and parsed within the retinal circuitry. First, we propose to identify the limiting source of noise in the rod photoreceptors that sets visual threshold by utilizing mouse models with reduced rod noise. We will compare how reduced noise influences the detection of single photon responses, and how it influences the behavioral threshold for seeing. The limiting noise in rods reflects a key control point within rod phototransduction that sets absolute visual threshold. Second, we propose to characterize the properties of rod-driven signals in the primary rod pathway and determine how sensitivity is modulated during adaptation to background light. Finally, we propose to characterize how cone bipolar cells integrate rod-driven signals generated by the primary and secondary rod pathways, along with cone-driven signals, using mice where either rod or cone phototransduction has been silenced. These experiments will allow us to dissect how rod-driven signals in many parallel pathways combine with cone-driven signals to define the dynamic range of rod vision. Our long-term goal is to provide a comprehensive understanding of the mechanisms that control the transmission of rod-driven signals to higher visual centers. This work is aligned with the objectives of the Retinal Diseases Program of the NEI "to use molecular and physiological approaches to identify post photoreceptor neural components of adaptation", which will be key to understanding the pathophysiology associated with deficits in rod vision.

Public Health Relevance

In mammals rod vision is not only sufficiently sensitive to encode few photon absorptions in the array of rods near visual threshold, but can also operate up to light levels where its function is merged with the cone system. This wide dynamic range, encompassing 100,000,000-fold differences in light intensity, is the result of physiological mechanisms and multiple rod retinal pathways that enhance the properties of signals with respect to noise when background light levels are low, but can also adapt to the mean illumination as background light levels increase. This proposal is aimed at elucidating the functional properties of the rod circuitry that produce this dynamic range, and in understanding how these contribute to rod vision.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017606-07
Application #
8306747
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
2006-08-01
Project End
2016-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
7
Fiscal Year
2012
Total Cost
$410,000
Indirect Cost
$160,000
Name
University of Southern California
Department
Physiology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Mao, Wen; Miyagishima, K J; Yao, Yun et al. (2013) Functional comparison of rod and cone G*(t) on the regulation of light sensitivity. J Biol Chem 288:5257-67
Chen, Shih-Kuo; Chew, Kylie S; McNeill, David S et al. (2013) Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment. Neuron 77:503-15
Majumder, Anurima; Pahlberg, Johan; Boyd, Kimberly K et al. (2013) Transducin translocation contributes to rod survival and enhances synaptic transmission from rods to rod bipolar cells. Proc Natl Acad Sci U S A 110:12468-73
Arman, A Cyrus; Sampath, Alapakkam P (2012) Dark-adapted response threshold of OFF ganglion cells is not set by OFF bipolar cells in the mouse retina. J Neurophysiol 107:2649-59
Cao, Yan; Pahlberg, Johan; Sarria, Ignacio et al. (2012) Regulators of G protein signaling RGS7 and RGS11 determine the onset of the light response in ON bipolar neurons. Proc Natl Acad Sci U S A 109:7905-10
Pahlberg, Johan; Sampath, Alapakkam P (2011) Visual threshold is set by linear and nonlinear mechanisms in the retina that mitigate noise: how neural circuits in the retina improve the signal-to-noise ratio of the single-photon response. Bioessays 33:438-47
Okawa, Haruhisa; Pahlberg, Johan; Rieke, Fred et al. (2010) Coordinated control of sensitivity by two splice variants of G?(o) in retinal ON bipolar cells. J Gen Physiol 136:443-54
Matthews, Hugh R; Sampath, Alapakkam P (2010) Photopigment quenching is Ca2+ dependent and controls response duration in salamander L-cone photoreceptors. J Gen Physiol 135:355-66
Okawa, Haruhisa; Miyagishima, K Joshua; Arman, A Cyrus et al. (2010) Optimal processing of photoreceptor signals is required to maximize behavioural sensitivity. J Physiol 588:1947-60
Arman, A Cyrus; Sampath, Alapakkam P (2010) Patch clamp recordings from mouse retinal neurons in a dark-adapted slice preparation. J Vis Exp :

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