biostudies-literatureUnknownLefton KBNIDDK NIH HHSNIMH NIH HHSNINDS NIH HHSLocus coeruleus (LC)-derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit connectivity, but the underlying synapse-level mechanisms are elusive. Here, we show that NE remodeling of synaptic function is independent from its binding on neuronal receptors. Instead, astrocytic adrenergic receptors and Ca²⁺ dynamics fully gate the effect of NE on synapses as the astrocyte-specific deletion of adrenergic receptors and three independent astrocyte-silencing approaches all render synapses insensitive to NE. Additionally, we find that NE suppression of synaptic strength results from an ATP-derived and adenosine A1 receptor-mediated control of presynaptic efficacy. An accompanying study from Chen et al. reveals the existbioRxiv : the preprint server for biology2024.05.21.595135https://www.ebi.ac.uk/biostudies/studies/S-EPMC11142048biostudies-literatureNorepinephrine Signals Through Astrocytes To Modulate Synapses.PMC11142048R01 NS102272R01 MH127163R01 DK128475Walsh SSamineni VKPapouin TLefton KBYen AZhang YOkuda TDougherty JDManno RSimpson PCWu YDai YfalseNorepinephrine Signals Through Astrocytes To Modulate Synapses.Locus coeruleus (LC)-derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit connectivity, but the underlying synapse-level mechanisms are elusive. Here, we show that NE remodeling of synaptic function is independent from its binding on neuronal receptors. Instead, astrocytic adrenergic receptors and Ca²⁺ dynamics fully gate the effect of NE on synapses as the astrocyte-specific deletion of adrenergic receptors and three independent astrocyte-silencing approaches all render synapses insensitive to NE. Additionally, we find that NE suppression of synaptic strength results from an ATP-derived and adenosine A1 receptor-mediated control of presynaptic efficacy. An accompanying study from Chen et al. reveals the exist2024-01-01T00:00:00Z2024 May2026-04-24T03:18:18.329Z2026-04-24T03:09:46.776ZS-EPMC111420483882620910.1101/2024.05.21.595135