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Updated: Aug 26, 2025

Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
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Distinct phosphorylation states of mammalian CaMKIIβ control the induction and maintenance of sleep

Daisuke Tone1,2, Koji L Ode1,2, Qianhui Zhang2

  • 1Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Osaka, Japan.

Plos Biology
|October 4, 2022
PubMed

Insights

Calcium/calmodulin-dependent protein kinase II beta (CaMKIIβ) acts as a core sleep regulator. Its kinase activity and phosphorylation states control sleep induction and maintenance, proposing a new "phosphorylation hypothesis of sleep".

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Sleep Science

Background:

  • Reduced sleep duration in Camk2b knockout mice suggests Ca2+/calmodulin-dependent protein kinase II beta (CaMKIIβ) is a sleep-promoting kinase.
  • The precise mechanism of CaMKIIβ in sleep regulation remains largely unelucidated.

Purpose of the Study:

  • To investigate the role and mechanism of CaMKIIβ in mammalian sleep regulation.
  • To determine if CaMKIIβ kinase activity is essential for its sleep-regulatory function.

Main Methods:

  • Utilizing Camk2b knockout mice and specific CaMKIIβ mutants.
  • Manipulating CaMKIIβ activity (activation/inhibition) and phosphorylation states in vivo.
  • Measuring sleep duration and transitions between sleep and awake states.

Main Results:

  • CaMKIIβ activation/inhibition altered mouse sleep duration by nearly 2-fold.
  • Sleep regulation by CaMKIIβ is dependent on its kinase activity.
  • Constitutively active CaMKIIβ promoted sleep onset, while other phosphorylation mutants affected sleep-wake transitions.

Conclusions:

  • CaMKIIβ is a core regulator of mammalian sleep.
  • Different phosphorylation states of CaMKIIβ differentially regulate sleep induction and maintenance.
  • A novel
  • phosphorylation hypothesis of sleep
  • is proposed for molecular sleep control.

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