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Electrical and synaptic integration of glioma into neural circuits

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; Woo, Pamelyn J.; Taylor, Kathryn R.; Agarwal, Amit; Regev, Aviv; Brang, David; Vogel, Hannes; Hervey-Jumper, Shawn; Bergles, Dwight E.; Suvà, Mario L.; Malenka, Robert C.; Monje, Michelle; ... Show more Show less
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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.
Date issued
2019-09
URI
https://hdl.handle.net/1721.1/126741
Department
Massachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MIT
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
ISSN
0028-0836
1476-4687

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