Neuromedin S-producing Neurons Act As Essential Pacemakers in the Suprachiasmatic Nucleus to Couple Clock Neurons and Dictate Circadian Rhythms

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2015 Mar 6

PMID 25741729

Citations 96

Authors

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

Affiliations

Soon will be listed here.

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 is sufficient 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 in vivo 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 in vivo circadian rhythms through intercellular synaptic transmission.

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