Neuromedin s-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms

Ivan T. Lee, Alexander S. Chang, Manabu Manandhar, Yongli Shan, Junmei Fan, Mariko Izumo, Yuichi Ikeda, Toshiyuki Motoike, Shelley Dixon, Jeffrey E. Seinfeld, Joseph S. Takahashi, Masashi Yanagisawa

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Abstract

Circadian behavior in mammals is orchestrated by neurons within the suprachiasmatic nucleus (SCN), yet the neuronal population necessary for the generation of timekeeping remains unknown. We show that a subset of SCN neurons expressing the neuropeptide neuromedin S (NMS) plays an essential role in the generation of daily rhythms in behavior. We demonstrate that lengthening period within Nms neurons issufficient to lengthen period of the SCN and behavioral circadian rhythms. Conversely, mice without a functional molecular clock within Nms neurons lack synchronous molecular oscillations and coherent behavioral daily rhythms. Interestingly, we found that mice lacking Nms and its closely related paralog, Nmu, do not lose invivo circadian rhythms. However, blocking vesicular transmission from Nms neurons with intact cell-autonomous clocks disrupts the timing mechanisms of the SCN, revealing that Nms neurons define a subpopulation of pacemakers that control SCN network synchrony and invivo circadian rhythms through intercellular synaptic transmission.

Original languageEnglish (US)
Pages (from-to)1086-1102
Number of pages17
JournalNeuron
Volume85
Issue number5
DOIs
StatePublished - Mar 4 2015

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Suprachiasmatic Nucleus
Circadian Rhythm
Neurons
Neuropeptides
Synaptic Transmission
Mammals
Population

ASJC Scopus subject areas

  • Neuroscience(all)

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Neuromedin s-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms. / Lee, Ivan T.; Chang, Alexander S.; Manandhar, Manabu; Shan, Yongli; Fan, Junmei; Izumo, Mariko; Ikeda, Yuichi; Motoike, Toshiyuki; Dixon, Shelley; Seinfeld, Jeffrey E.; Takahashi, Joseph S.; Yanagisawa, Masashi.

In: Neuron, Vol. 85, No. 5, 04.03.2015, p. 1086-1102.

Research output: Contribution to journalArticle

Lee, Ivan T. ; Chang, Alexander S. ; Manandhar, Manabu ; Shan, Yongli ; Fan, Junmei ; Izumo, Mariko ; Ikeda, Yuichi ; Motoike, Toshiyuki ; Dixon, Shelley ; Seinfeld, Jeffrey E. ; Takahashi, Joseph S. ; Yanagisawa, Masashi. / Neuromedin s-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms. In: Neuron. 2015 ; Vol. 85, No. 5. pp. 1086-1102.
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