Norepinephrine changes behavioral state through astroglial purinergic signaling
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.
Authors
- Emmanuel Márquez-Legorreta (ORCID: https://orcid.org/0000-0001-6729-9404)
- Xuelong Mi
- Claire Wyart (ORCID: https://orcid.org/0000-0002-1668-4975)
- Marc Duque (ORCID: https://orcid.org/0000-0003-2999-4283)
- Misha B. Ahrens (ORCID: https://orcid.org/0000-0002-3457-4462)
- David A. Prober (ORCID: https://orcid.org/0000-0002-7371-4675)
- Mark Eddison (ORCID: https://orcid.org/0000-0003-0280-8137)
- Guoqiang Yu (ORCID: https://orcid.org/0000-0002-6743-7413)
- Mahalakshmi Dhanasekar (ORCID: https://orcid.org/0000-0002-7979-061X)
- Alex Chen (ORCID: https://orcid.org/0000-0003-3950-4460)
- Florian Engert (ORCID: https://orcid.org/0000-0001-8169-2990)
- Vickie M. Wang (ORCID: https://orcid.org/0000-0001-7138-0096)
- Sujatha Narayan (ORCID: https://orcid.org/0000-0002-3741-1319)
- Altyn Rymbek
- Loeva Tocquer
Institutions
- California Institute of Technology (US)
- Allen Institute for Brain Science (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Inserm (FR)
- Janelia Research Campus (US)
- Sorbonne Université (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Allen Institute (US)
- Institut du Cerveau (FR)
- Virginia Tech (US)
- Tsinghua University (CN)
Publication Details
- Journal
- Science
- Published
- 2025-05-15
- DOI
- https://doi.org/10.1126/science.adq5233
- Citations
- 41
- Primary Topic
- Zebrafish Biomedical Research Applications
- Type
- article
- Field-Weighted Citation Impact
- 47.21