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Electrical and synaptic integration of glioma into neural circuits

Author

Listed:
  • Humsa S. Venkatesh

    (Stanford University)

  • Wade Morishita

    (Stanford University
    Stanford University)

  • Anna C. Geraghty

    (Stanford University)

  • Dana Silverbush

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of Harvard and MIT
    Broad Institute of Harvard and MIT)

  • Shawn M. Gillespie

    (Stanford University)

  • Marlene Arzt

    (Stanford University)

  • Lydia T. Tam

    (Stanford University)

  • Cedric Espenel

    (Stanford University School of Medicine)

  • Anitha Ponnuswami

    (Stanford University)

  • Lijun Ni

    (Stanford University)

  • Pamelyn J. Woo

    (Stanford University)

  • Kathryn R. Taylor

    (Stanford University)

  • Amit Agarwal

    (Johns Hopkins University
    Heidelberg University)

  • Aviv Regev

    (Broad Institute of Harvard and MIT
    Broad Institute of Harvard and MIT
    MIT)

  • David Brang

    (University of Michigan)

  • Hannes Vogel

    (Stanford University
    Stanford University
    Stanford University)

  • Shawn Hervey-Jumper

    (University of California, San Francisco)

  • Dwight E. Bergles

    (Johns Hopkins University)

  • Mario L. Suvà

    (Massachusetts General Hospital and Harvard Medical School
    Broad Institute of Harvard and MIT
    Broad Institute of Harvard and MIT)

  • Robert C. Malenka

    (Stanford University
    Stanford University)

  • Michelle Monje

    (Stanford University
    Stanford University
    Stanford University
    Stanford University)

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.

Suggested Citation

  • Humsa S. Venkatesh & Wade Morishita & Anna C. Geraghty & Dana Silverbush & Shawn M. Gillespie & Marlene Arzt & Lydia T. Tam & Cedric Espenel & Anitha Ponnuswami & Lijun Ni & Pamelyn J. Woo & Kathryn R, 2019. "Electrical and synaptic integration of glioma into neural circuits," Nature, Nature, vol. 573(7775), pages 539-545, September.
    • Handle: RePEc:nat:nature:v:573:y:2019:i:7775:d:10.1038_s41586-019-1563-y
    DOI: 10.1038/s41586-019-1563-y
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    Cited by:

    1. Ling Hai & Dirk C. Hoffmann & Robin J. Wagener & Daniel D. Azorin & David Hausmann & Ruifan Xie & Magnus-Carsten Huppertz & Julien Hiblot & Philipp Sievers & Sophie Heuer & Jakob Ito & Gina Cebulla & , 2024. "A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1," Nature Communications, Nature, vol. 15(1), pages 1-29, December.
    2. Yanming Ren & Zongyao Huang & Lingling Zhou & Peng Xiao & Junwei Song & Ping He & Chuanxing Xie & Ran Zhou & Menghan Li & Xiangqun Dong & Qing Mao & Chao You & Jianguo Xu & Yanhui Liu & Zhigang Lan & , 2023. "Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Alexander Popov & Nadezda Brazhe & Kseniia Morozova & Konstantin Yashin & Maxim Bychkov & Olga Nosova & Oksana Sutyagina & Alexey Brazhe & Evgenia Parshina & Li Li & Igor Medyanik & Dmitry E. Korzhevs, 2023. "Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Corina Anastasaki & Juan Mo & Ji-Kang Chen & Jit Chatterjee & Yuan Pan & Suzanne M. Scheaffer & Olivia Cobb & Michelle Monje & Lu Q. Le & David H. Gutmann, 2022. "Neuronal hyperexcitability drives central and peripheral nervous system tumor progression in models of neurofibromatosis-1," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Yuanning Zheng & Francisco Carrillo-Perez & Marija Pizurica & Dieter Henrik Heiland & Olivier Gevaert, 2023. "Spatial cellular architecture predicts prognosis in glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. William H. Tomaszewski & Jessica Waibl-Polania & Molly Chakraborty & Jonathan Perera & Jeremy Ratiu & Alexandra Miggelbrink & Donald P. McDonnell & Mustafa Khasraw & David M. Ashley & Peter E. Fecci &, 2022. "Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Chaitali Chakraborty & Itzel Nissen & Craig A. Vincent & Anna-Carin Hägglund & Andreas Hörnblad & Silvia Remeseiro, 2023. "Rewiring of the promoter-enhancer interactome and regulatory landscape in glioblastoma orchestrates gene expression underlying neurogliomal synaptic communication," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Romain Sigaud & Thomas K. Albert & Caroline Hess & Thomas Hielscher & Nadine Winkler & Daniela Kocher & Carolin Walter & Daniel Münter & Florian Selt & Diren Usta & Jonas Ecker & Angela Brentrup & Mar, 2023. "MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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