This proposal is aimed at understanding the properties of the rod circuitry in the mammalian retina. Our rod vision encompasses lights as dim as a single photon absorption in as many as 10,000 rod photoreceptors, up to 1000 or more photons per rod. This wide range of light sensitivity is accomplished by biophysical mechanisms that have been studied for more than a half century, but several outstanding issues of fundamental importance remain. The experiments described in this proposal are designed to address two issues: (1) Which aspects of the rod photoresponse are relevant for downstream processing?, and (2) What are the threshold and dynamic range of light intensities for each retinal pathway that relays the rod photoresponse to ganglion cells? To answer these questions we will record light-evoked responses from rod photoreceptors, bipolar cells and ganglion cells from several transgenic mouse lines lacking cone light responses (cone trasducin -/-) with: (1) knockouts in the rod phototransduction pathway that change the shape of the rod photoresponse, and (2) knockouts in the retinal circuitry that will allow the rod retinal pathways (Rod-Bipolar, Rod-Cone, and Rod-Off pathways) to be studied in isolation. The deletion of the phototransduction proteins (GCAP, Rhodopsin Kinase, Rhodopsin, and Arrestin), or the gap junction protein Connexin 36 in specific cells, will alter the transmission of light responses and allow us to infer how the properties of the photoresponse and circuitry influence rod vision. In parallel with these experiments, we will evaluate the behavioral threshold for rod vision in each mouse studied. Thus alterations in the physiology of rod signaling in the retina can be connected to a constrained and quantifiable visual behavior. Such correlations will provide insights into how the processing of the rod photoresponse influences perception, and will have consequences for understanding the mechanistic basis for deficits in rod vision (i.e. Stationary Night Blindness). ? ? Night vision in mammals is mediated by several pathways in the retina that relay information about few photon absorptions to the brain. This proposal is aimed at understanding how this remarkable sensitivity is achieved at the cellular level by establishing the properties of the rod photoreceptor response and the retinal circuitry that are important for visual processing. In order to devise therapies for conditions that influence our night vision, like Stationary Night Blindness, it is necessary to first understand the physiological mechanisms that relay information from our eyes to our brain at low light levels. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY017606-01
Application #
7131802
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Mariani, Andrew P
Project Start
2006-08-01
Project End
2011-06-30
Budget Start
2006-08-01
Budget End
2007-06-30
Support Year
1
Fiscal Year
2006
Total Cost
$337,896
Indirect Cost
Name
University of Southern California
Department
Physiology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Pahlberg, Johan; Frederiksen, Rikard; Pollock, Gabriel E et al. (2017) Voltage-sensitive conductances increase the sensitivity of rod photoresponses following pigment bleaching. J Physiol 595:3459-3469
Wang, Yuchen; Fehlhaber, Katherine E; Sarria, Ignacio et al. (2017) The Auxiliary Calcium Channel Subunit ?2?4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors. Neuron 93:1359-1374.e6
Field, Greg D; Sampath, Alapakkam P (2017) Behavioural and physiological limits to vision in mammals. Philos Trans R Soc Lond B Biol Sci 372:
Majumder, Anurima; Pahlberg, Johan; Muradov, Hakim et al. (2015) Exchange of Cone for Rod Phosphodiesterase 6 Catalytic Subunits in Rod Photoreceptors Mimics in Part Features of Light Adaptation. J Neurosci 35:9225-35
Cao, Yan; Sarria, Ignacio; Fehlhaber, Katherine E et al. (2015) Mechanism for Selective Synaptic Wiring of Rod Photoreceptors into the Retinal Circuitry and Its Role in Vision. Neuron 87:1248-1260
Sarria, Ignacio; Pahlberg, Johan; Cao, Yan et al. (2015) Sensitivity and kinetics of signal transmission at the first visual synapse differentially impact visually-guided behavior. Elife 4:e06358
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
Reingruber, Jürgen; Pahlberg, Johan; Woodruff, Michael L et al. (2013) Detection of single photons by toad and mouse rods. Proc Natl Acad Sci U S A 110:19378-83
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

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