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Nat Commun. 2020 Jan 24;11(1):471. doi: 10.1038/s41467-020-14378-x.

Distinct temporal integration of noradrenaline signaling by astrocytic second messengers during vigilance.

Author information

1
RIKEN Center for Brain Science, Wako, Saitama, Japan. oe@brain.riken.jp.
2
RIKEN Center for Brain Science, Wako, Saitama, Japan.
3
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
4
Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA.
5
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
6
Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland.
7
Viral Vector Core, Gunma University Initiative for Advanced Research, Maebashi, Gunma, 371-8511, Japan.
8
Department of Neurophysiology & Neural Repair, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
9
RIKEN Center for Brain Science, Wako, Saitama, Japan. hirase@sund.ku.dk.
10
Center for Translational Neuromedicine, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark. hirase@sund.ku.dk.
11
Brain and Body System Science Institute, Saitama University, Saitama, Japan. hirase@sund.ku.dk.

Abstract

Astrocytes may function as mediators of the impact of noradrenaline on neuronal function. Activation of glial α1-adrenergic receptors triggers rapid astrocytic Ca2+ elevation and facilitates synaptic plasticity, while activation of β-adrenergic receptors elevates cAMP levels and modulates memory consolidation. However, the dynamics of these processes in behaving mice remain unexplored, as do the interactions between the distinct second messenger pathways. Here we simultaneously monitored astrocytic Ca2+ and cAMP and demonstrate that astrocytic second messengers are regulated in a temporally distinct manner. In behaving mice, we found that while an abrupt facial air puff triggered transient increases in noradrenaline release and large cytosolic astrocytic Ca2+ elevations, cAMP changes were not detectable. By contrast, repeated aversive stimuli that lead to prolonged periods of vigilance were accompanied by robust noradrenergic axonal activity and gradual sustained cAMP increases. Our findings suggest distinct astrocytic signaling pathways can integrate noradrenergic activity during vigilance states to mediate distinct functions supporting memory.

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