title: Sustained activation of GABAA receptors in the suprachiasmatic nucleus mediates light-induced phase delays of the circadian clock: a novel function of ionotropic receptors.
abstract: The suprachiasmatic nucleus (SCN) contains a circadian clock that generates endogenous rhythmicity and entrains that rhythmicity with the day-night cycle. The neurochemical events that transduce photic input within the SCN and mediate entrainment by resetting the molecular clock have yet to be defined. Because GABA is contained in nearly all SCN neurons we tested the hypothesis that GABA serves as this signal in studies employing Syrian hamsters (Mesocricetus auratus). Activation of GABAA receptors was found to be necessary and sufficient for light to induce phase delays of the clock. Remarkably, the sustained activation of GABAA receptors for more than three consecutive hours was necessary to phase-delay the clock. The duration of GABAA receptor activation required to induce phase delays would not have been predicted by either the prevalent theory of circadian entrainment or by expectations regarding the duration of ionotropic receptor activation necessary to produce functional responses. Taken together, these data identify a novel neurochemical mechanism essential for phase-delaying the 'master' circadian clock within the SCN as well as identifying an unprecedented action of an amino acid neurotransmitter involving the sustained activation of ionotropic receptors.
authors: Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA, USA.|Department of Psychology, Morehouse College, Atlanta, GA, USA.
authors: Daniel L
authors: DL
authors: Hummer
authors: Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA, USA.|Neuroscience Institute, Georgia State University, Atlanta, GA, USA.|Neuroscience Institute, Department of Neurobiology, Morehouse School of Medicine, Atlanta, GA, USA.
authors: J Christopher
authors: JC
authors: Ehlen
authors: Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA, USA.|Department of Psychology, Morehouse College, Atlanta, GA, USA.|Neuroscience Institute, Georgia State University, Atlanta, GA, USA.
authors: Tony E
authors: TE
authors: Larkin
authors: Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA, USA.|Neuroscience Institute, Georgia State University, Atlanta, GA, USA.
authors: John K
authors: JK
authors: McNeill
authors: Department of Psychology, Morehouse College, Atlanta, GA, USA.
authors: John R
authors: JR
authors: Pamplin
authors: Department of Psychology, Morehouse College, Atlanta, GA, USA.
authors: Colton A
authors: CA
authors: Walker
authors: Department of Psychology, Morehouse College, Atlanta, GA, USA.
authors: Phillip V
authors: PV
authors: Walker
authors: Department of Psychology, Morehouse College, Atlanta, GA, USA.
authors: Daryl R
authors: DR
authors: Dhanraj
authors: Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA, USA.|Neuroscience Institute, Georgia State University, Atlanta, GA, USA.
authors: H Elliott
authors: HE
authors: Albers
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D057906:Circadian Clocks / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D018682:GABA Agents / Q000494:pharmacology; D008027:Light; D008297:Male; D008647:Mesocricetus; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D011963:Receptors, GABA-A / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018682:GABA Agents; D011963:Receptors, GABA-A; D009118:Muscimol; D001640:Bicuculline
keywords: entrainment; hamster; neurotransmission; pacemaker; photic