GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior

Takashi Maejima, Yusuke Tsuno, Shota Miyazaki, Yousuke Tsuneoka, Emi Hasegawa, Md Tarikul Islam, Ryosuke Enoki, Takahiro J. Nakamura, Michihiro Mieda

Research output: Contribution to journalArticlepeer-review

Abstract

The suprachiasmatic nucleus (SCN), the central circadian pacemaker in mammals, is a network structure composed of multiple types of γ-aminobutyric acid (GABA)-ergic neurons and glial cells. However, the roles of GABA-mediated signaling in the SCN network remain controversial. Here, we report noticeable impairment of the circadian rhythm in mice with a specific deletion of the vesicular GABA transporter in arginine vasopressin (AVP)-producing neurons. These mice showed disturbed diurnal rhythms of GABAA receptor-mediated synaptic transmission in SCN neurons and marked lengthening of the activity time in circadian behavioral rhythms due to the extended interval between morning and evening locomotor activities. Synchrony of molecular circadian oscillations among SCN neurons did not significantly change, whereas the phase relationships between SCN molecular clocks and circadian morning/evening locomotor activities were altered significantly, as revealed by PER2::LUC imaging of SCN explants and in vivo recording of intracellular Ca2+ in SCN AVP neurons. In contrast, daily neuronal activity in SCN neurons in vivo clearly showed a bimodal pattern that correlated with dissociated morning/evening locomotor activities. Therefore, GABAergic transmission from AVP neurons regulates the timing of SCN neuronal firing to temporally restrict circadian behavior to appropriate time windows in SCN molecular clocks.

Original languageEnglish
Article numbere2010168118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number6
DOIs
Publication statusPublished - 9 Feb 2021

Keywords

  • Arginine vasopressin
  • Circadian rhythm
  • GABA
  • Suprachiasmatic nucleus

Fingerprint Dive into the research topics of 'GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior'. Together they form a unique fingerprint.

Cite this