Norepinephrine changes behavioral state through astroglial purinergic signaling.

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-05-15 DOI:10.1126/science.adq5233

Alex B Chen, Marc Duque, Altyn Rymbek, Mahalakshmi Dhanasekar, Vickie M Wang, Xuelong Mi, Loeva Tocquer, Sujatha Narayan, Emmanuel Marquez Legorreta, Mark Eddison, Guoqiang Yu, Claire Wyart, David A Prober, Florian Engert, Misha B Ahrens

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Abstract

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.

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去甲肾上腺素通过星形胶质嘌呤能信号改变行为状态。

神经元和神经胶质都通过扩散性神经调节剂进行交流；然而，这种神经调节网络中的神经元-胶质相互作用如何影响电路计算和行为尚不清楚。在斑马鱼幼体的效用诱导行为转变过程中，神经调节剂去甲肾上腺素（NE）驱动行为和回路活动的快速兴奋和延迟抑制。我们发现星形胶质嘌呤能信号传导实现了该基序的抑制臂。在斑马鱼幼体中，NE触发星形胶质细胞释放三磷酸腺苷（ATP），细胞外ATP转化为腺苷，并通过激活后脑神经元腺苷受体来抑制行为。我们的研究结果表明，一个进化上保守的星形胶质嘌呤能信号轴在ne介导的行为和脑状态转变中具有计算和行为作用，并将星形胶质细胞定位为神经调节信号的重要效应器。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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