期刊
JOURNAL OF NEUROSCIENCE
卷 35, 期 34, 页码 11791-11810出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0651-15.2015
关键词
astrocytes; cerebral cortex; cyclooxygenase-2; interneurons; pyramidal cells
资金
- Human Frontier Science Program [RGY0070/2007]
- Agence Nationale pour la Recherche [ANR 2011 MALZ 003 01]
- IHU Institut de Neurosciences Translationelles de Paris [ANR-10-IAIHU-06]
- Fondation pour la Recherche sur le Cerveau/Rotary Club de France [AOE-7]
- Canadian Institutes of Health Research (CIHR) [MOP-84209, MOP-1267]
- Heart and Stroke Foundation of Canada
- Heart and Stroke Foundation of British Columbia and Yukon
- Heart and Stroke Foundation of Yukon
- Djavad Mowafaghian Centre for Brain Health
- France Alzheimer (ASTROinAD)
- Deutsche Forschungsgemeinschaft [CRC1039 A3]
- Fondation pour la Recherche Medicale fellowship [FDT20100920106]
Vasodilatory prostaglandins play a key role in neurovascular coupling (NVC), the tight link between neuronal activity and local cerebral blood flow, but their precise identity, cellular origin and the receptors involved remain unclear. Here we show in rats that NMDA-induced vasodilation and hemodynamic responses evoked by whisker stimulation involve cyclooxygenase-2 (COX-2) activity and activation of the prostaglandin E2 (PgE(2)) receptors EP2 and EP4. Using liquid chromatography-electrospray ionization-tandem mass spectrometry, we demonstrate that PgE(2) is released by NMDA in cortical slices. The characterization of PgE2 producing cells by immunohistochemistry and single-cell reverse transcriptase-PCR revealed that pyramidal cells and not astrocytes are the main cell type equipped for PgE2 synthesis, one third expressing COX-2 systematically associated with a PgE2 synthase. Consistent with their central role in NVC, in vivo optogenetic stimulation of pyramidal cells evoked COX-2-dependent hyperemic responses in mice. These observations identify PgE2 as the main prostaglandin mediating sensory-evoked NVC, pyramidal cells as their principal source and vasodilatory EP2 and EP4 receptors as their targets.
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