Astrocytic IP3/Ca2+ Signaling Modulates Theta Rhythm and REM Sleep.

Jeannine Foley,Philip Haydon,Christophe Erneux,Soyoung Lee,Tamara Blutstein,Michael M Halassa

doi:10.3389/fncir.2017.00003

Abstract

Rapid eye movement (REM) sleep onset is triggered by disinhibition of cholinergic neurons in the pons. During REM sleep, the brain exhibits prominent activity in the 5–8 Hz (theta) frequency range. How REM sleep onset and theta waves are regulated is poorly understood. Astrocytes, a non-neuronal cell type in the brain, respond to cholinergic signals by elevating their intracellular Ca2+ concentration. The goal of this study was to assess the sleep architecture of mice with attenuated IP3 mediated Ca2+ signaling in astrocytes. Vigilance states and cortical electroencephalograph power were measured in wild type mice and mice with attenuated IP3/Ca2+ signaling. Attenuating IP3/Ca2+ signaling specifically in astrocytes caused mice to spend more time in REM sleep and enter this state more frequently during their inactive phase. These mice also exhibited greater power in the theta frequency range. These data suggest a role for astrocytic IP3/Ca2+ signaling in modulating REM sleep and the associated physiological state of the cortex.

Highlights

IntroductionEach vigilance state: rapid eye movement (REM) or paradoxical sleep, non-Rapid eye movement (REM) (NREM) sleep, and wake can be distinguished by neuronal synchronization measured by electroencephalography (EEG) and the level of movement detected by electromyography (EMG)
The major aspects of sleep architecture are conserved from rodent to human
We have previously demonstrated that SNARE-mediated release of gliotransmitters from astrocytes is necessary for sleep homeostasis (Halassa et al, 2009; Schmitt et al, 2012)

Summary

Introduction

Each vigilance state: rapid eye movement (REM) or paradoxical sleep, non-REM (NREM) sleep, and wake can be distinguished by neuronal synchronization measured by electroencephalography (EEG) and the level of movement detected by electromyography (EMG). The EEG shows increased synchrony during NREM sleep and is dominated by slow wave activity (SWA) in the 0.5–4 Hz range. REM sleep is similar to wake, with a desynchronized EEG but prominent hippocampal theta activity in the 5–8 Hz frequency range (Platt and Riedel, 2011). Upon natural transition into REM sleep, cholinergic projection neurons in the pons become disinhibited and drive theta oscillations in the hippocampus (McCarley and Massaquoi, 1992; Buzsàki, 2002; McCarley, 2007). Experimental activation of pontine neurons using optogenetics (Van Dort et al, 2015) or cholinergic agonists (Bezzi et al, 1998) increases time spent in REM sleep. Hippocampal astrocytes express cholinergic receptors that elicit calcium transients when stimulated (Shen and Yakel, 2012)

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