title: The Circadian Oscillator of the Cerebral Cortex: Molecular, Biochemical and Behavioral Effects of Deleting the Arntl Clock Gene in Cortical Neurons.
abstract: A molecular circadian oscillator resides in neurons of the cerebral cortex, but its role is unknown. Using the Cre-LoxP method, we have here abolished the core clock gene Arntl in those neurons. This mouse represents the first model carrying a deletion of a circadian clock component specifically in an extrahypothalamic cell type of the brain. Molecular analyses of clock gene expression in the cerebral cortex of the Arntl conditional knockout mouse revealed disrupted circadian expression profiles, whereas clock gene expression in the suprachiasmatic nucleus was still rhythmic, thus showing that Arntl is required for normal function of the cortical circadian oscillator. Daily rhythms in running activity and temperature were not influenced, whereas the resynchronization response to experimental jet-lag exhibited minor though significant differences between genotypes. The tail-suspension test revealed significantly prolonged immobility periods in the knockout mouse indicative of a depressive-like behavioral state. This phenotype was accompanied by reduced norepinephrine levels in the cerebral cortex. Our data show that Arntl is required for normal cortical clock function and further give reason to suspect that the circadian oscillator of the cerebral cortex is involved in regulating both circadian biology and mood-related behavior and biochemistry.
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.|Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen, Mental Health Services of the Capital Region of Denmark, DK-2100 Copenhagen, Denmark.
authors.forename: Tenna
authors.initials: T
authors.lastname: Bering
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Mikkel Bloss
authors.initials: MB
authors.lastname: Carstensen
authors.affiliation: Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1014 Copenhagen, Denmark.
authors.forename: Gitta
authors.initials: G
authors.lastname: Wörtwein
authors.affiliation: Laboratory of Neuropsychiatry, Psychiatric Center Copenhagen, Mental Health Services of the Capital Region of Denmark, DK-2100 Copenhagen, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Weikop
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Martin Fredensborg
authors.initials: MF
authors.lastname: Rath
mesh_terms: D056930:ARNTL Transcription Factors / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism*; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D003863:Depression / Q000378:metabolism / Q000523:psychology; D005260:Female; D008124:Locomotion / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D056925:Circadian Rhythm Signaling Peptides and Proteins
keywords: circadian; clock gene; conditional knockout; hippocampus; neocortex