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.
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Mishra Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles AAM.pdf Download (13MB) | Preview |
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.
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