1. Rhythmic astrocytic GABA production synchronizes neuronal circadian timekeeping in the suprachiasmatic nucleus.
- Author
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Ness, Natalie, Díaz-Clavero, Sandra, Hoekstra, Marieke M B, and Brancaccio, Marco
- Subjects
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SUPRACHIASMATIC nucleus , *MAMMAL behavior , *CIRCADIAN rhythms , *SLEEP-wake cycle , *GABA - 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. Synopsis: Astrocytes can drive circadian behavior in mammals, but the nature of the temporal information generated by astrocytes is largely unknown. This study identifies GABA produced by polyamine degradation in astrocytes as a critical signal that synchronizes neuronal activity in the suprachiasmatic nucleus (SCN), which orchestrates circadian rhythms in mammals. Circadian phases of astrocytic activity are uniform across the SCN, in contrast to the phase waves of neuronal activity. Extracellular GABA levels in the SCN peak during the nighttime, mirroring the spatiotemporal organization of astrocytic rhythms, as opposed to the daytime peak of neuronal activity. Inhibition of synaptic GABA release desynchronizes neuronal circadian rhythms in the SCN, but does not affect extracellular GABA rhythms. Inhibition of astrocytic GABA synthesis disrupts circadian rhythms of extracellular GABA and desynchronizes neuronal circadian activity, suggesting a role as an internal circadian synchronizer for the SCN circuit ("astrozeit"). Inhibitory nighttime GABA produced via rhythmic polyamine degradation in astrocytes synchronizes neuronal circadian rhythms. [ABSTRACT FROM AUTHOR]
- Published
- 2025
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