Stellate neurons mediate functional hyperemia in the cerebellar molecular layer.
Mice lacking cyclin D2 have a profound reduction in the number of stellate neurons in the cerebellar molecular layer. We used cyclin D2-null mice to study the contribution of stellate neurons 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 stimulation of the upper lip (5-30 V; 10 Hz), and BFcrb was recorded at the activated site by the use of a laser-Doppler flow probe. In wild-type mice, upper lip stimulation increased BFcrb in crus II by 32 +/- 2%. The rise in BFcrb was attenuated by 19% in heterozygous mice and by 69% in homozygous mice. In contrast to the cerebellum, the increases in somatosensory cortex blood flow produced by upper lip stimulation was not attenuated in D2-null mice. The field potentials evoked in crus II by upper lip stimulation did not differ between wild-type and D2-null mice. Stellate neurons are a major source of nitric oxide (NO) in the cerebellar molecular layer. The neuronal NO synthase inhibitor 7-nitroindazole attenuated the vascular response to crus II activation in wild-type mice but not in D2-null mice, suggesting that stellate neurons are the major source of NO mediating the vascular response. The data provide evidence that stellate neurons are a critical link between neural activity and blood flow in the activated cerebellum and that NO is the principal effector of their vascular actions.
Yang
G
G
Center for Clinical and Molecular Neurobiology, Department of Neurology, School of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Huard
J M
JM
Beitz
A J
AJ
Ross
M E
ME
Iadecola
C
C
D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D002531:Cerebellum / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D056742:Cyclin D2; D016213:Cyclins / Q000172:deficiency / Q000235:genetics; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D017078:Laser-Doppler Flowmetry; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D013003:Somatosensory Cortex / Q000098:blood supply / Q000502:physiology; D014276:Trigeminal Nerve / Q000166:cytology / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse