Author
Listed:
- Ana Badimon
(Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai)
- Hayley J. Strasburger
(Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai)
- Pinar Ayata
(Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai)
- Xinhong Chen
(California Institute of Technology)
- Aditya Nair
(California Institute of Technology)
- Ako Ikegami
(Nagoya University Graduate School of Medicine
Kobe University Graduate School of Medicine)
- Philip Hwang
(Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai)
- Andrew T. Chan
(Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai)
- Steven M. Graves
(University of Minnesota)
- Joseph O. Uweru
(University of Virginia)
- Carola Ledderose
(Beth Israel Deaconess Medical Center, Harvard Medical School)
- Munir Gunes Kutlu
(Vanderbilt University)
- Michael A. Wheeler
(Brigham and Women’s Hospital, Harvard Medical School)
- Anat Kahan
(California Institute of Technology)
- Masago Ishikawa
(Icahn School of Medicine at Mount Sinai)
- Ying-Chih Wang
(Icahn Institute of Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai)
- Yong-Hwee E. Loh
(Icahn School of Medicine at Mount Sinai)
- Jean X. Jiang
(University of Texas Health Science Center)
- D. James Surmeier
(Northwestern University)
- Simon C. Robson
(Beth Israel Deaconess Medical Center and Harvard Medical School
Beth Israel Deaconess Medical Center and Harvard Medical School)
- Wolfgang G. Junger
(Beth Israel Deaconess Medical Center, Harvard Medical School)
- Robert Sebra
(Icahn Institute of Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai)
- Erin S. Calipari
(Vanderbilt University
Vanderbilt University
Vanderbilt University
Vanderbilt University)
- Paul J. Kenny
(Icahn School of Medicine at Mount Sinai)
- Ukpong B. Eyo
(University of Virginia)
- Marco Colonna
(Washington University School of Medicine)
- Francisco J. Quintana
(Brigham and Women’s Hospital, Harvard Medical School
The Broad Institute of MIT and Harvard)
- Hiroaki Wake
(Nagoya University Graduate School of Medicine
Kobe University Graduate School of Medicine)
- Viviana Gradinaru
(California Institute of Technology)
- Anne Schaefer
(Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai)
Abstract
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 survival1. 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.
Suggested Citation
Ana Badimon & Hayley J. Strasburger & Pinar Ayata & Xinhong Chen & Aditya Nair & Ako Ikegami & Philip Hwang & Andrew T. Chan & Steven M. Graves & Joseph O. Uweru & Carola Ledderose & Munir Gunes Kutlu, 2020.
"Negative feedback control of neuronal activity by microglia,"
Nature, Nature, vol. 586(7829), pages 417-423, October.
Handle:
RePEc:nat:nature:v:586:y:2020:i:7829:d:10.1038_s41586-020-2777-8
DOI: 10.1038/s41586-020-2777-8
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Cited by:
- Péter Berki & Csaba Cserép & Zsuzsanna Környei & Balázs Pósfai & Eszter Szabadits & Andor Domonkos & Anna Kellermayer & Miklós Nyerges & Xiaofei Wei & Istvan Mody & Araki Kunihiko & Heinz Beck & He Ka, 2024.
"Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices,"
Nature Communications, Nature, vol. 15(1), pages 1-24, December.
- George Sideris-Lampretsas & Silvia Oggero & Lynda Zeboudj & Rita Silva & Archana Bajpai & Gopuraja Dharmalingam & David A. Collier & Marzia Malcangio, 2023.
"Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease,"
Nature Communications, Nature, vol. 14(1), pages 1-19, December.
- Danyang Chen & Qianqian Lou & Xiang-Jie Song & Fang Kang & An Liu & Changjian Zheng & Yanhua Li & Di Wang & Sen Qun & Zhi Zhang & Peng Cao & Yan Jin, 2024.
"Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice,"
Nature Communications, Nature, vol. 15(1), pages 1-15, December.
- Robyn P. Araujo & Lance A. Liotta, 2023.
"Universal structures for adaptation in biochemical reaction networks,"
Nature Communications, Nature, vol. 14(1), pages 1-12, December.
- Noah R. Johnson & Peng Yuan & Erika Castillo & T. Peter Lopez & Weizhou Yue & Annalise Bond & Brianna M. Rivera & Miranda C. Sullivan & Masakazu Hirouchi & Kurt Giles & Atsushi Aoyagi & Carlo Condello, 2023.
"CSF1R inhibitors induce a sex-specific resilient microglial phenotype and functional rescue in a tauopathy mouse model,"
Nature Communications, Nature, vol. 14(1), pages 1-23, December.
- Nicholas J. Silva & Leah C. Dorman & Ilia D. Vainchtein & Nadine C. Horneck & Anna V. Molofsky, 2021.
"In situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain,"
Nature Communications, Nature, vol. 12(1), pages 1-12, December.
- Katia Monsorno & Kyllian Ginggen & Andranik Ivanov & An Buckinx & Arnaud L. Lalive & Anna Tchenio & Sam Benson & Marc Vendrell & Angelo D’Alessandro & Dieter Beule & Luc Pellerin & Manuel Mameli & Ros, 2023.
"Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice,"
Nature Communications, Nature, vol. 14(1), pages 1-18, December.
- I. Hristovska & M. Robert & K. Combet & J. Honnorat & J-C Comte & O. Pascual, 2022.
"Sleep decreases neuronal activity control of microglial dynamics in mice,"
Nature Communications, Nature, vol. 13(1), pages 1-15, December.
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