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  Negative feedback control of neuronal activity by microglia

Badimon, A., Strasburger, H. J., Ayata, P., Chen, X., Nair, A., Ikegami, A., et al. (2020). Negative feedback control of neuronal activity by microglia. Nature, 586(7829), 417-423. doi:10.1038/s41586-020-2777-8.

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Genre: Zeitschriftenartikel

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https://www.ncbi.nlm.nih.gov/pubmed/32999463 (beliebiger Volltext)
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 Urheber:
Badimon, A., Autor
Strasburger, H. J., Autor
Ayata, P., Autor
Chen, X., Autor
Nair, A., Autor
Ikegami, A., Autor
Hwang, P., Autor
Chan, A. T., Autor
Graves, S. M., Autor
Uweru, J. O., Autor
Ledderose, C., Autor
Kutlu, M. G., Autor
Wheeler, M. A., Autor
Kahan, A., Autor
Ishikawa, M., Autor
Wang, Y. C., Autor
Loh, Y. E., Autor
Jiang, J. X., Autor
Surmeier, D. J., Autor
Robson, S. C., Autor
Junger, W. G., AutorSebra, R., AutorCalipari, E. S., AutorKenny, P. J., AutorEyo, U. B., AutorColonna, M., AutorQuintana, F. J., AutorWake, H., AutorGradinaru, V., AutorSchaefer, A.1, Autor            mehr..
Affiliations:
1Department Schaefer - Neurobiology of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3393997              

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Schlagwörter: 5'-Nucleotidase/metabolism Action Potentials Adenosine/metabolism Adenosine Monophosphate/metabolism Adenosine Triphosphate/metabolism Animals Antigens, CD/metabolism Apyrase/metabolism Calcium/metabolism Corpus Striatum/cytology/physiology *Feedback, Physiological Female Humans Male Mice Mice, Inbred C57BL Microglia/cytology/*physiology *Neural Inhibition/genetics Neurons/*physiology Receptor, Adenosine A1/metabolism Receptor, Muscarinic M3/genetics/metabolism Time Factors
 Zusammenfassung: Microglia, the brain's resident macrophages, help to regulate brain function by removing dying neurons, pruning non-functional synapses, and producing ligands that support neuronal survival(1). Here we show that microglia are also critical modulators of neuronal activity and associated behavioural responses in mice. Microglia respond to neuronal activation by suppressing neuronal activity, and ablation of microglia amplifies and synchronizes the activity of neurons, leading to seizures. Suppression of neuronal activation by microglia occurs in a highly region-specific fashion and depends on the ability of microglia to sense and catabolize extracellular ATP, which is released upon neuronal activation by neurons and astrocytes. ATP triggers the recruitment of microglial protrusions and is converted by the microglial ATP/ADP hydrolysing ectoenzyme CD39 into AMP; AMP is then converted into adenosine by CD73, which is expressed on microglia as well as other brain cells. Microglial sensing of ATP, the ensuing microglia-dependent production of adenosine, and the adenosine-mediated suppression of neuronal responses via the adenosine receptor A1R are essential for the regulation of neuronal activity and animal behaviour. Our findings suggest that this microglia-driven negative feedback mechanism operates similarly to inhibitory neurons and is essential for protecting the brain from excessive activation in health and disease.

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 Datum: 2020-10-022020-10-02
 Publikationsstatus: Erschienen
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 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: Anderer: 32999463
DOI: 10.1038/s41586-020-2777-8
ISSN: 1476-4687 (Electronic)0028-0836 (Linking)
 Art des Abschluß: -

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Titel: Nature
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 586 (7829) Artikelnummer: - Start- / Endseite: 417 - 423 Identifikator: -