title: Opposing actions of neuropeptide Y and light on the expression of circadian clock genes in the mouse suprachiasmatic nuclei.
abstract: The circadian clockwork of the hypothalamic suprachiasmatic nuclei (SCN) is synchronized by light and by nonphotic cues. The core timing mechanism is cell-autonomous, based on an autoregulatory transcriptional/translational feedback loop of circadian genes and their products. This study investigated the effects of neuropeptide Y (NPY), a potent nonphotic resetting cue, and its interaction with light in regulating clock gene expression in the SCN in vivo. Injection of NPY adjacent to the SCN and transfer to darkness 7 h before scheduled lights out, shifted the circadian activity-rest cycle. Exposure to light for 1 h immediately after NPY infusion blocked this behavioural response. NPY-induced shifts were accompanied by suppression of both mPer1 and mPer2 mRNA in the SCN, assessed 3 h after infusion. mPer mRNAs were not altered 1 h after infusion. Levels of mClock mRNA or mCLOCK immunoreactivity in the SCN were not affected by NPY at either time point. In parallel to the behavioural response, the NPY-induced suppression of mPer genes in the SCN was attenuated when a light pulse was delivered immediately after the infusion. These results identify mPer1 and mPer2 as molecular targets for both photic and nonphotic (NPY-induced) resetting of the clockwork, and support a synthetic model of circadian entrainment based upon convergent up- and downregulation of mPer expression.
authors.affiliation: Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, UK. emaywood@mrc-lmb.cam.ac.uk
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Maywood
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamura
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hastings
mesh_terms: D000818:Animals; D001345:Autoradiography; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D003463:Cues; D015536:Down-Regulation / Q000502:physiology; D008027:Light; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D015854:Up-Regulation / Q000502:physiology
chemical_list: D009478:Neuropeptide Y