Astrocytic GABA produced from polyamines synchronizes neuronal circadian timekeeping in the suprachiasmatic nucleus
Author(s)
Ness, Natalie
Diaz Clavero, Sandra
Hoekstra, Marieke
Brancaccio, Marco
Type
Journal Article
Abstract
Astrocytes of the suprachiasmatic nucleus (SCN) can regulate sleep-wake cycles in mammals. However, the nature of the information provided by astrocytes to control circadian patterns of behavior is unclear. Neuronal circadian activity across the SCN is organized into spatiotemporal waves that govern seasonal adaptations and timely engagement of behavioral outputs. Here, we show that astrocytes across the mouse SCN exhibit instead a highly uniform, pulse-like nighttime activity. We find that rhythmic astrocytic GABA production via polyamine degradation provides an inhibitory nighttime tone required for SCN circuit synchrony, thereby acting as an internal astrocyte zeitgeber (or “astrozeit”). We further identify synaptic GABA and astrocytic GABA as two key players underpinning coherent spatiotemporal circadian patterns of SCN neuronal activity. In describing a new mechanism by which astrocytes contribute to circadian timekeeping, our work provides a general blueprint for understanding how astrocytes encode temporal information underlying complex behaviors in mammals.
Date Issued
2025-01-16
Date Acceptance
2024-11-04
Citation
The EMBO Journal, 2025, 44 (2), pp.356-381
ISSN
0261-4189
Publisher
EMBO Press
Start Page
356
End Page
381
Journal / Book Title
The EMBO Journal
Volume
44
Issue
2
Copyright Statement
© 2024 The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39623138
PII: 10.1038/s44318-024-00324-w
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Circadian Clock
Astrocyte
GABA
MAO-B
SCN
MONOAMINE-OXIDASE-B
CLOCK
RELEASE
MOUSE
PLASTICITY
LOCALIZATION
TRANSPORTERS
OSCILLATIONS
EXPRESSION
TIME
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2024-12-02