title: Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles.
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+]iis 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.
authors: Department of Neuroscience, Physiology &Pharmacology, University College London, London, UK.
authors: Anusha
authors: A
authors: Mishra
authors: Institute of Neurology, University College London, London, UK.
authors: James P
authors: JP
authors: Reynolds
authors: Department of Neuroscience, Physiology &Pharmacology, University College London, London, UK.
authors: Yang
authors: Y
authors: Chen
authors: Department of Neuroscience, Physiology &Pharmacology, University College London, London, UK.
authors: Alexander V
authors: AV
authors: Gourine
authors: Institute of Neurology, University College London, London, UK.
authors: Dmitri A
authors: 0000-0001-9539-9947
authors: DA
authors: Rusakov
authors: Department of Neuroscience, Physiology &Pharmacology, University College London, London, UK.
authors: David
authors: 0000-0003-3618-0843
authors: D
authors: Attwell
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors