Norepinephrine signals through astrocytes to modulate synapses
Locus ceruleus (LC)-derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit functional connectivity, but the underlying synapse-level mechanisms are elusive. Here, we show that NE remodeling of synaptic function is completely independent from its binding on neuronal receptors. Instead, astrocytic adrenergic receptors and calcium dynamics fully gate the effect of NE on synapses. Additionally, we found that NE suppression of synaptic strength results from an adenosine 5'-triphosphate (ATP)-derived and A1 adenosine receptor-mediated control of presynaptic efficacy. These findings suggest that astrocytes are a core component of neuromodulatory systems and the circuit effector through which NE produces network and behavioral adaptations.
Authors
- Sarah Walsh
- Yifan Wu (ORCID: https://orcid.org/0000-0003-0028-8457)
- Katheryn B. Lefton (ORCID: https://orcid.org/0000-0002-1434-7385)
- Gareth M. Rurak (ORCID: https://orcid.org/0000-0003-4477-1969)
- Vijay K. Samineni (ORCID: https://orcid.org/0000-0002-9491-2793)
- Thomas Papouin (ORCID: https://orcid.org/0000-0001-5288-1944)
- Allen Yen (ORCID: https://orcid.org/0000-0002-3984-541X)
- Yanchao Dai (ORCID: https://orcid.org/0000-0001-6169-514X)
- Joseph D. Dougherty (ORCID: https://orcid.org/0000-0002-6385-3997)
- Rachel Manno
- Takao Okuda
- Yufen Zhang (ORCID: https://orcid.org/0000-0003-3306-4193)
- Paul Simpson (ORCID: https://orcid.org/0000-0003-2234-8633)
- Bat‐Erdene Myagmar
Institutions
- San Francisco VA Medical Center (US)
- Washington University in St. Louis (US)
Publication Details
- Journal
- Science
- Published
- 2025-05-15
- DOI
- https://doi.org/10.1126/science.adq5480
- Citations
- 52
- Primary Topic
- Neuroscience and Neuropharmacology Research
- Type
- article
- Field-Weighted Citation Impact
- 47.27