title: Role for the NR2B subunit of the N-methyl-D-aspartate receptor in mediating light input to the circadian system.
abstract: Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that utilize glutamate as a neurotransmitter. A variety of evidence suggests that the release of glutamate then activates N-methyl-D-aspartate (NMDA) receptors within the SCN and triggers a signaling cascade that ultimately leads to phase shifts in the circadian system. In this study, we first sought to explore the role of the NR2B subunit in mediating the effects of light on the circadian system of hamsters and mice. We found that localized microinjection of the NR2B subunit antagonist ifenprodil into the SCN region reduces the magnitude of light-induced phase shifts of the circadian rhythm in wheel-running activity. Next, we found that the NR2B message and levels of phospho-NR2B vary with time of day in SCN tissue using semiquantitative real-time polymerase chain reaction and western blot analysis, respectively. Functionally, we found that blocking the NR2B subunit with ifenprodil significantly reduced the magnitude of NMDA currents recorded in SCN neurons. Ifenprodil also significantly reduced the magnitude of NMDA-induced Ca2+ changes in SCN cells. Together, these results demonstrate that the NR2B subunit is an important component of NMDA receptor-mediated responses within SCN neurons and that this subunit contributes to light-induced phase shifts of the mammalian circadian system.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California-Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024-1759, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Schroeder
authors.forename: D
authors.initials: D
authors.lastname: Loh
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: K
authors.initials: K
authors.lastname: Lin
authors.forename: J H
authors.initials: JH
authors.lastname: Han
authors.forename: S
authors.initials: S
authors.lastname: Michel
authors.forename: D L
authors.initials: DL
authors.lastname: Hummer
authors.forename: J C
authors.initials: JC
authors.lastname: Ehlen
authors.forename: H E
authors.initials: HE
authors.lastname: Albers
authors.forename: C S
authors.initials: CS
authors.lastname: Colwell
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation / Q000379:methods*; D010880:Piperidines / Q000494:pharmacology; D021122:Protein Subunits / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: C121001:NR2B NMDA receptor; D010880:Piperidines; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; C010739:ifenprodil