The dorsomedial hypothalamic nucleus as a putative food-entrainable circadian pacemaker

Michihiro Mieda, S. Clay Williams, James A. Richardson, Kohichi Tanaka, Masashi Yanagisawa

Research output: Contribution to journalArticlepeer-review

244 Scopus citations


Temporal restriction of feeding can phase-shift behavioral and physiological circadian rhythms in mammals. These changes in biological rhythms are postulated to be brought about by a food-entrainable oscillator (FEO) that is independent of the suprachiasmatic nucleus. However, the neural substrates of FEO have remained elusive. Here, we carried out an unbiased search for mouse brain region(s) that exhibit a rhythmic expression of the Period genes in a feeding-entrainable manner. We found that the compact part of the dorsomedial hypothalamic nucleus (DMH) demonstrates a robust oscillation of mPer expression only under restricted feeding. The oscillation persisted for at least 2 days even when mice were given no food during the expected feeding period after the establishment of food-entrained behavioral rhythms. Moreover, refeeding after fasting rapidly induced a transient mPer expression in the same area of DMH. Taken in conjunction with recent findings (i) that behavioral expression of food-entrainable circadian rhythms is blocked by cell-specific lesions of DMH in rats and (ii) that DMH neurons directly project to orexin neurons in the lateral hypothalamus, which are essential for proper expression of food-entrained behavioral rhythms, the present study suggests that DMH plays a key role as a central FEO in the feeding-mediated regulation of circadian behaviors.

Original languageEnglish (US)
Pages (from-to)12150-12155
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number32
StatePublished - Aug 8 2006


  • Circadian rhythm
  • Feeding
  • Mouse
  • Obesity
  • Period

ASJC Scopus subject areas

  • General


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