Document Detail


Circadian rhythm of contrast sensitivity is regulated by a dopamine-neuronal PAS-domain protein 2-adenylyl cyclase 1 signaling pathway in retinal ganglion cells.
MedLine Citation:
PMID:  24048828     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Spatial variation in light intensity, called spatial contrast, comprises much of the visual information perceived by mammals, and the relative ability to detect contrast is referred to as contrast sensitivity (Purves et al., 2012). Recently, retinal dopamine D4 receptors (D4Rs) have been implicated in modulating contrast sensitivity (Jackson et al., 2012); however, the cellular and molecular mechanisms have not been elucidated. Our study demonstrates a circadian rhythm of contrast sensitivity that peaks during the daytime, and that its regulation involves interactions of D4Rs, the clock gene Npas2, and the clock-controlled gene adenylyl cyclase 1 (Adcy1) in a subset of retinal ganglion cells (RGCs). Targeted disruption of the gene encoding D4Rs reduces the amplitude of the contrast sensitivity rhythm by reducing daytime sensitivity and abolishes the rhythmic expression of Npas2 and Adcy1 mRNA in the ganglion cell layer (GCL) of the retina. Npas2(-/-) and Adcy1(-/-) mice show strikingly similar reductions in the contrast sensitivity rhythm to that in mice lacking D4Rs. Moreover, Adcy1 transcript rhythms were abolished in the GCL of Npas2(-/-) mice. Luciferase reporter assays demonstrated that the Adcy1 promoter is selectively activated by neuronal PAS-domain protein 2 (NPAS2)/BMAL1. Our results indicate that the contrast sensitivity rhythm is modulated by D4Rs via a signaling pathway that involves NPAS2-mediated circadian regulation of Adcy1. Hence, we have identified a circadian clock mechanism in a subset of RGCs that modulates an important aspect of retinal physiology and visual processing.
Authors:
Christopher K Hwang; Shyam S Chaurasia; Chad R Jackson; Guy C-K Chan; Daniel R Storm; P Michael Iuvone
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  33     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-09-19     Completed Date:  2013-11-26     Revised Date:  2014-03-21    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14989-97     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
ARNTL Transcription Factors / metabolism
Adenylate Cyclase / deficiency,  genetics
Animals
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism
Cell Line, Transformed
Circadian Rhythm / genetics,  physiology*
Contrast Sensitivity / genetics,  physiology*
Dopamine / metabolism*
Gene Expression Regulation / genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation / genetics
Nerve Tissue Proteins / genetics,  metabolism
Photic Stimulation
Receptors, Dopamine D4 / genetics,  metabolism
Retina
Retinal Ganglion Cells / metabolism*
Signal Transduction / physiology*
Transfection
Visual Acuity
Visual Pathways / physiology
beta-Galactosidase / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
F31 EY021089/EY/NEI NIH HHS; R01 EY004864/EY/NEI NIH HHS; R01 MH073601/MH/NIMH NIH HHS; R01 NS020498/NS/NINDS NIH HHS; T32 EY007092/EY/NEI NIH HHS; T32 GM008602/GM/NIGMS NIH HHS; T32 GM008602/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/ARNTL Transcription Factors; 0/Arntl protein, mouse; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Nerve Tissue Proteins; 0/Npas2 protein, mouse; 137750-34-6/Receptors, Dopamine D4; EC 3.2.1.23/beta-Galactosidase; EC 4.6.1.1/Adenylate Cyclase; EC 4.6.1.1/adenylyl cyclase 1; VTD58H1Z2X/Dopamine
Comments/Corrections

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