title: Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo.
abstract: BACKGROUND
  In mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions.
  
  
  METHODS
  We examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2) gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC) knock-in mice using a real-time bioluminescence measurement system.
  
  
  RESULTS
  Administration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms.
  
  
  CONCLUSIONS
  These findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.
authors.affiliation: Department of Biological Sciences and Brain Research Center for 21st Frontier Program in Neuroscience, Seoul National University College of Natural Sciences, Seoul, Korea.
authors.forename: Jinmi
authors.initials: J
authors.lastname: Koo
authors.affiliation: Department of Biological Sciences and Brain Research Center for 21st Frontier Program in Neuroscience, Seoul National University College of Natural Sciences, Seoul, Korea.
authors.forename: Han Kyoung
authors.initials: HK
authors.lastname: Choe
authors.affiliation: Department of Biological Sciences and Brain Research Center for 21st Frontier Program in Neuroscience, Seoul National University College of Natural Sciences, Seoul, Korea.|Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Korea.
authors.forename: Hee Dae
authors.initials: HD
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences and Brain Research Center for 21st Frontier Program in Neuroscience, Seoul National University College of Natural Sciences, Seoul, Korea.|Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Korea.
authors.forename: Sung Kook
authors.initials: SK
authors.lastname: Chun
authors.affiliation: Department of Biological Sciences and Brain Research Center for 21st Frontier Program in Neuroscience, Seoul National University College of Natural Sciences, Seoul, Korea.|Department of Legal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Gi Hoon
authors.initials: GH
authors.lastname: Son
authors.affiliation: Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Korea.|Department of Biological Sciences and Brain Research Center for 21st Frontier Program in Neuroscience, Seoul National University College of Natural Sciences, Seoul, Korea. kyungjin@dgist.ac.kr.
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Kim
keywords: Circadian rhythm; Gap junctions; Mefloquine; Per2; Real-time bioluminescence; Suprachiasmatic nucleus