Lhx1 maintains synchrony among circadian oscillator neurons of the SCN

  1. Megumi Hatori
  2. Shubhroz Gill
  3. Ludovic S Mure
  4. Martyn Goulding
  5. Dennis DM O'Leary
  6. Satchidananda Panda  Is a corresponding author
  1. Keio University, Japan
  2. Salk Institute for Biological Studies, United States

Abstract

The robustness and limited plasticity of the master circadian clock in the suprachiasmatic nucleus (SCN) is attributed to strong intercellular communication among its constituent neurons. However, factors that specify this characteristic feature of the SCN are unknown. Here we identified Lhx1 as a regulator of SCN coupling. A phase-shifting light pulse causes acute reduction in Lhx1 expression and of its target genes that participate in SCN coupling. Mice lacking Lhx1 in the SCN have intact circadian oscillators, but reduced levels of coupling factors. Consequently, the mice rapidly phase shift under a jet lag paradigm and their behavior rhythms gradually deteriorate under constant condition. Ex vivo recordings of the SCN from these mice showed rapid desynchronization of unit oscillators. Therefore, by regulating expression of genes mediating intercellular communication, Lhx1 imparts synchrony among SCN neurons and ensures consolidated rhythms of activity and rest that is resistant to photic noise.

Article and author information

Author details

  1. Megumi Hatori

    Keio University, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Shubhroz Gill

    Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ludovic S Mure

    Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Martyn Goulding

    Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dennis DM O'Leary

    Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Satchidananda Panda

    Salk Institute for Biological Studies, La Jolla, United States
    For correspondence
    panda@salk.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#12-00026) of the Salk Institute for Biological Studies. The protocol was approved by the IACUC committee of the Salk Institute. All surgery was performed under IACUC approved anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Louis Ptáček, University of California, San Francisco, United States

Publication history

  1. Received: May 13, 2014
  2. Accepted: July 10, 2014
  3. Accepted Manuscript published: July 17, 2014 (version 1)
  4. Version of Record published: August 20, 2014 (version 2)

Copyright

© 2014, Hatori et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Megumi Hatori
  2. Shubhroz Gill
  3. Ludovic S Mure
  4. Martyn Goulding
  5. Dennis DM O'Leary
  6. Satchidananda Panda
(2014)
Lhx1 maintains synchrony among circadian oscillator neurons of the SCN
eLife 3:e03357.
https://doi.org/10.7554/eLife.03357
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