Electrical and synaptic integration of glioma into neural circuits
Name
Venkatesh et al_article 070219.pdf
Description
Accepted version
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285.65 KB
Format
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Checksum (MD5)
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Author(s)
Venkatesh, Humsa S.
Morishita, Wade
Geraghty, Anna C.
Silverbush, Dana
Gillespie, Shawn M.
Arzt, Marlene
Tam, Lydia T.
Espenel, Cedric
Ponnuswami, Anitha
Ni, Lijun
Date Issued
September 2019
Journal
Nature
Publisher
Springer Science and Business Media LLC
Citation
Venkatesh, Humsa S. et al. "Electrical and synaptic integration of glioma into neural circuits." Nature 573, 7775 (September 2019): 539–545 © 2019 The Author(s)
Version
Author's final manuscript
Abstract
High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron–glioma synapses. Neuronal activity also evokes non-synaptic activity-dependent potassium currents that are amplified by gap junction-mediated tumour interconnections, forming an electrically coupled network. Depolarization of glioma membranes assessed by in vivo optogenetics promotes proliferation, whereas pharmacologically or genetically blocking electrochemical signalling inhibits the growth of glioma xenografts and extends mouse survival. Emphasizing the positive feedback mechanisms by which gliomas increase neuronal excitability and thus activity-regulated glioma growth, human intraoperative electrocorticography demonstrates increased cortical excitability in the glioma-infiltrated brain. Together, these findings indicate that synaptic and electrical integration into neural circuits promotes glioma progression.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41586-019-1563-y
