{"id":2363,"date":"2019-09-01T00:00:20","date_gmt":"2019-09-01T00:00:20","guid":{"rendered":"http:\/\/bergleslab.com\/?p=2363"},"modified":"2020-01-30T23:54:07","modified_gmt":"2020-01-30T23:54:07","slug":"venkatesh-2019","status":"publish","type":"post","link":"http:\/\/bergleslab.com\/index.php\/2019\/09\/01\/venkatesh-2019\/","title":{"rendered":"Electrical and synaptic integration of glioma into neural circuits."},"content":{"rendered":"
Nature.<\/a> 2019 Sep;573(7775):539-545. doi: 10.1038\/s41586-019-1563-y. Epub 2019 Sep 18.<\/div>\n

Electrical and synaptic integration of glioma into neural circuits.<\/h4>\n
Venkatesh HS<\/a>1<\/sup>, Morishita W<\/a>2,<\/sup>3<\/sup>, Geraghty AC<\/a>1<\/sup>, Silverbush D<\/a>4,<\/sup>5,<\/sup>6<\/sup>, Gillespie SM<\/a>1<\/sup>, Arzt M<\/a>1<\/sup>, Tam LT<\/a>1<\/sup>, Espenel C<\/a>7<\/sup>, Ponnuswami A<\/a>1<\/sup>, Ni L<\/a>1<\/sup>, Woo PJ<\/a>1<\/sup>, Taylor KR<\/a>1<\/sup>, Agarwal A<\/a>8,<\/sup>9<\/sup>, Regev A<\/a>5,<\/sup>6,<\/sup>10<\/sup>, Brang D<\/a>11<\/sup>, Vogel H<\/a>1,<\/sup>12,<\/sup>13<\/sup>, Hervey-Jumper S<\/a>14<\/sup>, Bergles DE<\/a>8<\/sup>, Suv\u00e0 ML<\/a>4,<\/sup>5,<\/sup>6<\/sup>, Malenka RC<\/a>2,<\/sup>3<\/sup>, Monje M<\/a>15,<\/sup>16,<\/sup>17,<\/sup>18,<\/sup>19<\/sup>.<\/div>\n
<\/div>\n

 <\/p>\n

ABSTRACT<\/h4>\n
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.<\/div>\n
<\/div>\n
<\/div>\n
<\/div>\n

1 Department of Neurology, Stanford University, Stanford, CA, USA.
\n2 Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
\n3 Nancy Pritzker Laboratory, Stanford University, Stanford, CA, USA.
\n4 Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
\n5 Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
\n6 Broad Institute of Harvard and MIT, Cambridge, MA, USA.
\n7 Cell Sciences Imaging Facility, Stanford University School of Medicine, Stanford, CA, USA.
\n8 Department of Neuroscience, Johns Hopkins University, Baltimore, MA, USA.
\n9 The Chica and Heinz Schaller Research Group, Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany.
\n10 Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA, USA.
\n11 Department of Psychology, University of Michigan, Ann Arbor, MI, USA.
\n12 Department of Pathology, Stanford University, Stanford, CA, USA.
\n13 Department of Pediatrics, Stanford University, Stanford, CA, USA.
\n14 Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
\n15 Department of Neurology, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.
\n16 Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.
\n17 Department of Pathology, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.
\n18 Department of Pediatrics, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.
\n19 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.<\/p>\n

PDF<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

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.<\/p>\n","protected":false},"author":1,"featured_media":2364,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[78,33],"tags":[91,145],"class_list":["post-2363","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-original-research","category-publications","tag-ampa-receptor","tag-glioma"],"_links":{"self":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/2363","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/comments?post=2363"}],"version-history":[{"count":3,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/2363\/revisions"}],"predecessor-version":[{"id":2368,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/posts\/2363\/revisions\/2368"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/media\/2364"}],"wp:attachment":[{"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/media?parent=2363"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/categories?post=2363"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/bergleslab.com\/index.php\/wp-json\/wp\/v2\/tags?post=2363"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}