title: Neurovascular coupling in hippocampus is mediated via diffusion by neuronal-derived nitric oxide.
abstract: The coupling between neuronal activity and cerebral blood flow (CBF) is essential for normal brain function. The mechanisms behind this neurovascular coupling process remain elusive, mainly because of difficulties in probing dynamically the functional and coordinated interaction between neurons and the vasculature in vivo. Direct and simultaneous measurements of nitric oxide (NO) dynamics and CBF changes in hippocampus in vivo support the notion that during glutamatergic activation nNOS-derived NO induces a time-, space-, and amplitude-coupled increase in the local CBF, later followed by a transient increase in local O2 tension. These events are dependent on the activation of the NMDA-glutamate receptor and nNOS, without a significant contribution of endothelial-derived NO or astrocyte-neuron signaling pathways. Upon diffusion of NO from active neurons, the vascular response encompasses the activation of soluble guanylate cyclase. Hence, in the hippocampus, neurovascular coupling is mediated by nNOS-derived NO via a diffusional connection between active glutamatergic neurons and blood vessels.
authors.affiliation: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus, 3000-548 Coimbra, Portugal.
authors.forename: Cátia F
authors.initials: CF
authors.lastname: Lourenço
authors.affiliation: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus, 3000-548 Coimbra, Portugal.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Santos
authors.affiliation: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus, 3000-548 Coimbra, Portugal.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Barbosa
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Cadenas
authors.affiliation: Department of Biochemistry and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay.
authors.forename: Rafael
authors.initials: R
authors.lastname: Radi
authors.affiliation: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Health Sciences Campus, 3000-548 Coimbra, Portugal. Electronic address: laranjin@ci.uc.pt.
authors.forename: João
authors.initials: J
authors.lastname: Laranjinha
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D058256:Brain Waves / Q000502:physiology; D004789:Enzyme Activation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism*; D006624:Hippocampus / Q000098:blood supply* / Q000601:surgery; D008297:Male; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D010100:Oxygen; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase
chemical_list: D016166:Free Radical Scavengers; D018160:Receptors, Cytoplasmic and Nuclear; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018698:Glutamic Acid; D052248:Nitric Oxide Synthase Type I; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D010100:Oxygen
keywords: Brain; Free radicals; Functional hyperemia; Hippocampus; Neurons; Neurovascular coupling; Nitric oxide