Norepinephrine changes behavioral state through astroglial purinergic signaling

• 成果类型: Article
• 署名作者: Chen, Alex B.; Duque, Marc; Rymbek, Altyn; Dhanasekar, Mahalakshmi; Wang, Vickie M.; Mi, Xuelong; Tocquer, Loeva; Narayan, Sujatha; Legorreta, Emmanuel Marquez; Eddison, Mark; Yu, Guoqiang; Wyart, Claire; Prober, David A.; Engert, Florian; Ahrens, Misha B.
• 署名单位: Howard Hughes Medical Institute; Harvard University; Harvard University; Harvard Medical School; California Institute of Technology; Assistance Publique Hopitaux Paris (APHP); Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Virginia Polytechnic Institute & State University; Tsinghua University; Allen Institute for Brain Science
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9519
• DOI: 10.1126/science.adq5233
• 发表日期: 2025-05-15
• 页码: 769-775
• 关键词: central pattern generator; locus-coeruleus; cortical astrocytes; dependent release; neural circuit; adenosine; modulation; zebrafish; inhibition; transmission

摘要

Both neurons and glia communicate through diffusible neuromodulators; however, how neuron-glial interactions in such neuromodulatory networks influence circuit computation and behavior is unclear. During futility-induced behavioral transitions in the larval zebrafish, the neuromodulator norepinephrine (NE) drives fast excitation and delayed inhibition of behavior and circuit activity. We found that astroglial purinergic signaling implements the inhibitory arm of this motif. In larval zebrafish, NE triggers astroglial release of adenosine triphosphate (ATP), extracellular conversion of ATP into adenosine, and behavioral suppression through activation of hindbrain neuronal adenosine receptors. Our results suggest a computational and behavioral role for an evolutionarily conserved astroglial purinergic signaling axis in NE-mediated behavioral and brain state transitions and position astroglia as important effectors in neuromodulatory signaling.