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Nat Neurosci. 2016 Dec;19(12):1619-1627. doi: 10.1038/nn.4428. Epub 2016 Oct 24.

Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles.

Author information

1
Department of Neuroscience, Physiology &Pharmacology, University College London, London, UK.
2
Institute of Neurology, University College London, London, UK.

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 lipase 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.

PMID:
27775719
PMCID:
PMC5131849
DOI:
10.1038/nn.4428
[Indexed for MEDLINE]
Free PMC Article

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