title: The dorsomedial hypothalamic nucleus is not necessary for food-anticipatory circadian rhythms of behavior, temperature or clock gene expression in mice.
abstract: Circadian rhythms in mammals are regulated by a light-entrainable circadian pacemaker in the hypothalamic suprachiasmatic nucleus and food-entrainable oscillators located elsewhere in the brain and body. The dorsomedial hypothalamic nucleus (DMH) has been proposed to be the site of oscillators driving food-anticipatory circadian rhythms, but this is controversial. To further evaluate this hypothesis, we measured clock gene, temperature and activity rhythms in intact and DMH-ablated mice. A single 4-h midday feeding after an overnight fast induced mPer1 and mPer2 mRNA expression in the DMH, arcuate nucleus, nucleus of the solitary tract and area postrema, and reset daily rhythms of mPer1, mPer2 and mBMAL1 in the DMH, arcuate and neocortex. These rhythms persisted during 2 days of food deprivation after 12 days of scheduled daytime feeding. Acute induction of DMH mPer1 and mPer2 was N-methyl-D-aspartate (NMDA) receptor-dependent, whereas rhythmic expression after 6 days of restricted feeding was not. Thermal DMH lesions did not affect acute induction or rhythmic expression of clock genes in other brain regions in response to scheduled daytime feeding. DMH lesions attenuated mean daily activity levels and nocturnality but did not affect food-anticipatory rhythms of activity and body temperature in either light-dark or constant darkness. These results confirm that the DMH and other brain regions express circadian clock gene rhythms sensitive to daytime feeding schedules, but do not support the hypothesis that DMH oscillations drive food-anticipatory behavioral or temperature rhythms.
authors.affiliation: Department of Pharmacology and Brain Science, School of Human Sciences, Waseda University, Tokorozawa, Saitama, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Moriya
authors.forename: Reiko
authors.initials: R
authors.lastname: Aida
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Masao
authors.initials: M
authors.lastname: Doi
authors.forename: Naomi
authors.initials: N
authors.lastname: Hayasaka
authors.forename: Norimichi
authors.initials: N
authors.lastname: Nakahata
authors.forename: Ralph
authors.initials: R
authors.lastname: Mistlberger
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamura
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Shibata
mesh_terms: D056930:ARNTL Transcription Factors; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001831:Body Temperature / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D004302:Dorsomedial Hypothalamic Nucleus / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D019579:Neocortex / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins; D017440:Photoperiod; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017552:Solitary Nucleus / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C539022:PER1 protein, human; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse