title: Attenuation of activity-induced increases in cerebellar blood flow in mice lacking neuronal nitric oxide synthase.
abstract: We used mice deficient in neuronal nitric oxide (NO) synthase (nNOS) to specifically investigate the role of neuronal NO in the increase of cerebellar blood flow (BFcrb) produced by neural activation. Crus II, a region of the cerebellar cortex that receives trigeminal sensory afferents, was activated by low-intensity stimulation of the upper lip (5-25 V, 4-16 Hz) in anesthetized mice. BFcrb was recorded in Crus II by using a laser-Doppler flow probe. In wild-type mice, upper lip stimulation increased BFcrb in the Crus II by 28 +/- 3% (25 V, 10 Hz, n = 6). The rise in BFcrb was attenuated by 73 +/- 3% in nNOS-/- mice (P < 0.05, n = 6). The increases in BFcrb produced by superfusion of Crus II with glutamate or by systemic administration of harmaline were also attenuated in nNOS-/- mice (P < 0.05). In contrast, the increases in BFcrb produced by topical superfusion of Crus II with acetylcholine or adenosine and the increase in BFcrb produced by hypercapnia were not affected (P > 0.05). The field potentials evoked in the Crus II by upper lip stimulation did not differ between wild-type and nNOS-null mice. These data provide the first nonpharmacological evidence that nNOS-derived NO is a critical link between glutamatergic synaptic activity and blood flow in the activated cerebellum.
authors.affiliation: Department of Neuroloy and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Ross
authors.forename: Costantino
authors.initials: C
authors.lastname: Iadecola
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002525:Cerebellar Cortex / Q000098:blood supply / Q000502:physiology; D002531:Cerebellum / Q000098:blood supply* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology; D006246:Harmaline / Q000494:pharmacology; D006940:Hyperemia / Q000235:genetics / Q000503:physiopathology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009055:Mouth / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D010812:Physical Stimulation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D014665:Vasodilator Agents; D018698:Glutamic Acid; D006246:Harmaline; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D000241:Adenosine; D000109:Acetylcholine