Norepinephrine signals through astrocytes to modulate synapses

• 成果类型: Article
• 署名作者: Lefton, Katheryn B.; Wu, Yifan; Dai, Yanchao; Okuda, Takao; Zhang, Yufen; Yen, Allen; Rurak, Gareth M.; Walsh, Sarah; Manno, Rachel; Myagmar, Bat-Erdene; Dougherty, Joseph D.; Samineni, Vijay K.; Simpson, Paul C.; Papouin, Thomas
• 署名单位: Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); University of California System; University of California San Francisco; US Department of Veterans Affairs; Veterans Health Administration (VHA); San Francisco VA Medical Center; University of California System; University of California San Francisco; Washington University (WUSTL)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13184
• DOI: 10.1126/science.adq5480
• 发表日期: 2025-05-15
• 页码: 776-783
• 关键词: long-lasting potentiation; term synaptic depression; locus-coeruleus; cortical astrocytes; nmda-receptor; transmission; activation; neurons; acetylcholine; inhibition

摘要

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.