Vasoactive intestinal polypeptide requires parallel changes in adenylate cyclase and phospholipase C to entrain circadian rhythms to a predictable phase

Sungwon An, Robert P. Irwin, Charles N. Allen, Connie Tsai, Erik D. Herzog

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Circadian oscillations in the suprachiasmatic nucleus (SCN) depend on transcriptional repression by Period (PER)1 and PER2 proteins within single cells and on vasoactive intestinal polypeptide (VIP) signaling between cells. Because VIP is released by SCN neurons in a circadian pattern, and, after photic stimulation, it has been suggested to play a role in the synchronization to environmental light cycles. It is not known, however, if or how VIP entrains circadian gene expression or behavior. Here, we tested candidate signaling pathways required for VIPmediated entrainment of SCN rhythms. We found that single applications of VIP reset PER2 rhythms in a time- and dose-dependent manner that differed from light. Unlike VIP-mediated signaling in other cell types, simultaneous antagonism of adenylate cyclase and phospholipase C activities was required to block the VIP-induced phase shifts of SCN rhythms. Consistent with this, VIP rapidly increased intracellular cAMP in most SCN neurons. Critically, daily VIP treatment entrained PER2 rhythms to a predicted phase angle within several days, depending on the concentration of VIP and the interval between VIP applications. We conclude that VIP entrains circadian timing among SCN neurons through rapid and parallel changes in adenylate cyclase and phospholipase C activities.

Original languageEnglish (US)
Pages (from-to)2289-2296
Number of pages8
JournalJournal of neurophysiology
Volume105
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • Förster resonance energy transfer
  • Luciferase
  • Pacemaker
  • Period gene
  • Phase response curve

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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