Light has profound influences on many non-image forming visual functions (NIFs) including circadian rhythms, sleep, depression and pupillary light reflex. In mammals, light influences these NIFs through three photoreceptor types, namely the classical photoreceptors, rods and cones, and the intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin. As ganglion cells, ipRGCs transmit their own intrinsic light signals and also serve as the sole conduit to signal rod/cone information to brain regions important for these NIFs. However, the functional circuitry by which rods, cones and ipRGCs interact is poorly understood. Emerging evidence suggests that ipRGCs are much more complex than previously appreciated, consisting of multiple morphologically and electrophysiologically distinct subtypes. The functional significance of these different ipRGC subtypes remains unknown. We propose experiments to determine how rods, cones and ipRGCs interact to drive non-image-forming visual functions (Aim I), and to investigate the connectivity and function of the distinct ipRGC subtypes (Aim II and III). These studies will allow better understanding of the circuitry and physiological outcome of light effects on behaviors. This is of prime importance because light and the circadian clock temporally regulate many physiological parameters that influence sleep, depression, and general health in humans.

Public Health Relevance

In mammals, circadian photoentrainment is responsible for synchronizing many physiological rhythms to the solar day. Disruption of the regular 24-hour light/dark cycle, which can occur in shift work or jet-lag, leads to de-synchronization of the body's internal circadian clock from the solar day. Such de-synchrony is detrimental to human health not only causing sleep disorders, but is has also been implicated in many diseases ranging from depression to breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM076430-09
Application #
8536315
Study Section
Biological Rhythms and Sleep Study Section (BRS)
Program Officer
Sesma, Michael A
Project Start
2005-09-20
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
9
Fiscal Year
2013
Total Cost
$381,111
Indirect Cost
$145,922
Name
Johns Hopkins University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Prigge, Cameron L; Yeh, Po-Ting; Liou, Nan-Fu et al. (2016) M1 ipRGCs Influence Visual Function through Retrograde Signaling in the Retina. J Neurosci 36:7184-97
Fernandez, Diego Carlos; Chang, Yi-Ting; Hattar, Samer et al. (2016) Architecture of retinal projections to the central circadian pacemaker. Proc Natl Acad Sci U S A 113:6047-52
Keenan, William Thomas; Rupp, Alan C; Ross, Rachel A et al. (2016) A visual circuit uses complementary mechanisms to support transient and sustained pupil constriction. Elife 5:
Jaaro-Peled, Hanna; Altimus, Cara; LeGates, Tara et al. (2016) Abnormal wake/sleep pattern in a novel gain-of-function model of DISC1. Neurosci Res 112:63-69
Walker, Marquis T; Rupp, Alan; Elsaesser, Rebecca et al. (2015) RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells. Mol Biol Cell 26:3671-8
Gompf, Heinrich S; Fuller, Patrick M; Hattar, Samer et al. (2015) Impaired circadian photosensitivity in mice lacking glutamate transmission from retinal melanopsin cells. J Biol Rhythms 30:35-41
Xue, Yunlu; Shen, Susan Q; Jui, Jonathan et al. (2015) CRALBP supports the mammalian retinal visual cycle and cone vision. J Clin Invest 125:727-38
LeGates, Tara A; Fernandez, Diego C; Hattar, Samer (2014) Light as a central modulator of circadian rhythms, sleep and affect. Nat Rev Neurosci 15:443-54
Bedont, Joseph L; LeGates, Tara A; Slat, Emily A et al. (2014) Lhx1 controls terminal differentiation and circadian function of the suprachiasmatic nucleus. Cell Rep 7:609-22
Chew, Kylie S; Schmidt, Tiffany M; Rupp, Alan C et al. (2014) Loss of gq/11 genes does not abolish melanopsin phototransduction. PLoS One 9:e98356

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