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Cited by 543

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles

Open access
Mishra, Anusha, Reynolds, James P, Chen, Yang, Gourine, Alexander V, Rusakov, Dmitri A, Attwell, David·2016·Nature Neuroscience

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 Ca2+ 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 Ca2+ from stores does not affect neurovascular coupling. We now show that buffering astrocyte Ca2+ inhibits neuronally evoked capillary dilation, that astrocyte [Ca2+]i is raised not by release from stores but by entry through ATP-gated channels, and that Ca2+ generates arachidonic acid via phospholipase D2 and diacylglycerol kinase rather than phospholipase A2. In contrast, dilation of arterioles depends on NMDA receptor activation and Ca2+-dependent NO generation by interneurons. These results reveal that different signaling cascades regulate cerebral blood flow at the capillary and arteriole levels.

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Crossref · 10.1038/nn.4428

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Metadata

Authors
Mishra, A., Reynolds, J. P., Chen, Y., Gourine, A. V., Rusakov, D. A., & Attwell, D.
Venue
Nature Neuroscience
Published
2016-10-24
Volume
19
Issue
12
Pages
1619-1627
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2536398251
Cited by
543
References
7
FWCI
22.12
Type
journal article
Language
en
Open access
green

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