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Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles

Mishra, A; Reynolds, JP; Chen, Y; Gourine, AV; Rusakov, DA; Attwell, D; (2016) Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles. Nature Neuroscience , 19 (12) pp. 1619-1627. 10.1038/nn.4428. Green open access

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Abstract

Active neurons increase their energy supply by dilating nearby arterioles and capillaries. This neurovascular coupling underlies blood oxygen level-dependent functional imaging signals, but its mechanism is controversial. Canonically, neurons release glutamate to activate metabotropic glutamate receptor 5 (mGluR5) on astrocytes, evoking Ca(2+) release from internal stores, activating phospholipase A2 and generating vasodilatory arachidonic acid derivatives. However, adult astrocytes lack mGluR5, and knockout of the inositol 1,4,5-trisphosphate receptors that release Ca(2+) from stores does not affect neurovascular coupling. We now show that buffering astrocyte Ca(2+) inhibits neuronally evoked capillary dilation, that astrocyte [Ca(2+)]i is raised not by release from stores but by entry through ATP-gated channels, and that Ca(2+) generates arachidonic acid via phospholipase D2 and diacylglycerol kinase rather than phospholipase A2. In contrast, dilation of arterioles depends on NMDA receptor activation and Ca(2+)-dependent NO generation by interneurons. These results reveal that different signaling cascades regulate cerebral blood flow at the capillary and arteriole levels.

Type: Article
Title: Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nn.4428
Publisher version: http://dx.doi.org/10.1038/nn.4428
Language: English
Additional information: Copyright © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Keywords: Astrocyte; Neuro–vascular interactions
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1527239
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