title: Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.
abstract: As the central pacemaker in mammals, the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is a heterogeneous structure consisting of multiple types of GABAergic neurons with distinct chemical identities [1, 2]. Although individual cells have a cellular clock driven by autoregulatory transcriptional/translational feedback loops of clock genes, interneuronal communication among SCN clock neurons is likely essential for the SCN to generate a highly robust, coherent circadian rhythm [1]. However, neuronal mechanisms that determine circadian period length remain unclear. The SCN is composed of two subdivisions: a ventral core region containing vasoactive intestinal peptide (VIP)-producing neurons and a dorsal shell region characterized by arginine vasopressin (AVP)-producing neurons. Here we examined whether AVP neurons act as pacemaker cells that regulate the circadian period of behavior rhythm in mice. The deletion of casein kinase 1 delta (CK1δ) specific to AVP neurons, which was expected to lengthen the period of cellular clocks [3-6], lengthened the free-running period of circadian behavior as well. Conversely, the overexpression of CK1δ specific to SCN AVP neurons shortened the free-running period. PER2::LUC imaging in slices confirmed that cellular circadian periods of the SCN shell were lengthened in mice without CK1δ in AVP neurons. Thus, AVP neurons may be an essential component of circadian pacemaker cells in the SCN. Remarkably, the alteration of the shell-core phase relationship in the SCN of these mice did not impair the generation per se of circadian behavior rhythm, thereby underscoring the robustness of the SCN network.
authors: Department of Molecular Neuroscience and Integrative Physiology, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan. Electronic address: mieda@med.kanazawa-u.ac.jp.
authors: Michihiro
authors: M
authors: Mieda
authors: Laboratory for Developmental Gene Regulation, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors: Hitoshi
authors: H
authors: Okamoto
authors: Department of Molecular Neuroscience and Integrative Physiology, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan.
authors: Takeshi
authors: T
authors: Sakurai
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D047388:Casein Kinases / Q000235:genetics / Q000378:metabolism; D057906:Circadian Clocks; D002940:Circadian Rhythm; D005260:Female; D008124:Locomotion; D008297:Male; D051379:Mice; D009474:Neurons / Q000502:physiology*
chemical_list: D001127:Arginine Vasopressin; D047388:Casein Kinases