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Norepinephrine changes behavioral state via astroglial purinergic signaling

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Science. 2025 May 15;. doi: 10.1126/science.adq5233
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Norepinephrine changes behavioral state via astroglial purinergic signaling Ahrens Lab
Chen AB, Duque M, Wang VM, Dhanasekar M, Mi X, Rymbek A, Tocquer L, Narayan S, Prober D, Yu G, Wyart C, Engert F, Ahrens MB
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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.

 

Preprint: https://www.biorxiv.org/content/early/2024/05/23/2024.05.23.595576

PMID: 40373133 [PubMed - indexed for MEDLINE]

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Janelia Authors

Alex Chen
Sujatha Narayan
Misha Ahrens
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