title: Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum.
abstract: The tight coupling between increased neuronal activity and local cerebral blood flow, known as functional hyperemia, is essential for normal brain function. However, its cellular and molecular mechanisms remain poorly understood. In the cerebellum, functional hyperemia depends almost exclusively on nitric oxide (NO). Here, we investigated the role of different neuronal populations in the control of microvascular tone by in situ amperometric detection of NO and infrared videomicroscopy of microvessel movements in rat cerebellar slices. Bath application of an NO donor induced both NO flux and vasodilation. Surprisingly, endogenous release of NO elicited by glutamate was accompanied by vasoconstriction that was abolished by inhibition of Ca2+-phopholipase A2 and impaired by cyclooxygenase and thromboxane synthase inhibition and endothelin A receptor blockade, indicating a role for prostanoids and endothelin 1 in this response. Interestingly, direct stimulation of single endothelin 1-immunopositive Purkinje cells elicited constriction of neighboring microvessels. In contrast to glutamate, NMDA induced both NO flux and vasodilation that were abolished by treatment with a NO synthase inhibitor or with tetrodotoxin. These findings indicate that NO derived from neuronal origin is necessary for vasodilation induced by NMDA and, furthermore, that NO-producing interneurons mediate this vasomotor response. Correspondingly, electrophysiological stimulation of single nitrergic stellate cells by patch clamp was sufficient to release NO and dilate both intraparenchymal and upstream pial microvessels. These findings demonstrate that cerebellar stellate and Purkinje cells dilate and constrict, respectively, neighboring microvessels and highlight distinct roles for different neurons in neurovascular coupling.
authors.affiliation: Laboratoire de Neurobiologie et Diversité Cellulaire, Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 7637, Ecole Supérieure de Physique et de Chimie Industrielles de la ville de Paris, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Rancillac
authors.forename: Jean
authors.initials: J
authors.lastname: Rossier
authors.forename: Manon
authors.initials: M
authors.lastname: Guille
authors.forename: Xin-Kang
authors.initials: XK
authors.lastname: Tong
authors.forename: Hélène
authors.initials: H
authors.lastname: Geoffroy
authors.forename: Christian
authors.initials: C
authors.lastname: Amatore
authors.forename: Stéphane
authors.initials: S
authors.lastname: Arbault
authors.forename: Edith
authors.initials: E
authors.lastname: Hamel
authors.forename: Bruno
authors.initials: B
authors.lastname: Cauli
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011689:Purkinje Cells / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D006834:Hydrazines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D010069:Oxadiazoles; D011810:Quinoxalines; D009569:Nitric Oxide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine