Journal of Neurophysiology, Vol 75, Issue 2 940-950, Copyright © 1996 by APS

ARTICLES

Neural mechanisms of blood flow regulation during synaptic activity in cerebellar cortex

C. Iadecola, J. Li, S. Xu and G. Yang
Department of Neurology, University of Minnesota Medical School, Minneapolis 55455, USA.

1. We investigated the neural mechanisms of the increases in blood flow produced by synaptic activity using the parallel fiber (PF) system of the cerebellum as a model. The midline cerebellum was exposed in anesthetized rats and the PFs were stimulated with tungsten microelectrodes. Cerebellar blood flow (BFcrb) was recorded using a laser-Doppler probe, whereas field potentials were recorded using glass micropipettes. PF stimulation produced increases in BFcrb that were related to the frequency and intensity of stimulation (+60 +/- 9%, mean +/- SE, at 100 microA and 30 Hz; n = 6). The greatest increases were confined to a band stretching along the major axis of the stimulated folium and corresponding to the beam of activated PFs. The increase in evoked by PF stimulation was associated with a corresponding increase in glucose utilization, assessed by the 2-deoxyglucose method. The increases in BFcrb and the field potentials evoked by PF stimulation were abolished by tetrodotoxin (1 microM; n = 6). Ringer solution containing 12 mM Mg2+ and 0 mM Ca2+ blocked synaptic activity in the PFs and abolished the increases in flow (P > 0.05 from baseline; n = 5). The broad-spectrum glutamate receptor antagonist kynurenate (5 mM) prevented depolarization of Purkinje cells and interneurons and abolished the increase in BFcrb evoked by PF stimulation (P > 0.05; n = 6). Treatment with tetrodotoxin, Mg2+, or kynurenate did not affect the increase in BFcrb elicited by systemic hypercapnia or by topical application of the nitric oxide donor 3-morpholino sydnonimine (P > 0.05 from Ringer solution). We conclude that the increases in flow produced by synaptic activity are linked to glutamate-induced depolarization of Purkinje cells and interneurons. These findings provide evidence that activation of glutamate receptors participates in the mechanisms of functional hyperemia, and they support the validity of the PF system as a model for study of the relationship between synaptic activity and blood flow in the CNS.

This article has been cited by other articles:

				K. Caesar, P. Hashemi, A. Douhou, G. Bonvento, M. G. Boutelle, A. B. Walls, and M. Lauritzen Glutamate receptor-dependent increments in lactate, glucose and oxygen metabolism evoked in rat cerebellum in vivo J. Physiol., March 1, 2008; 586(5): 1337 - 1349. [Abstract] [Full Text] [PDF]

				C. W. Leffler, H. Parfenova, A. L. Fedinec, S. Basuroy, and D. Tcheranova Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigs Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2897 - H2904. [Abstract] [Full Text] [PDF]

				E. Chaigneau, M. Oheim, E. Audinat, and S. Charpak Two-photon imaging of capillary blood flow in olfactory bulb glomeruli PNAS, October 28, 2003; 100(22): 13081 - 13086. [Abstract] [Full Text] [PDF]

				M. Lauritzen and L. Gold Brain Function and Neurophysiological Correlates of Signals Used in Functional Neuroimaging J. Neurosci., May 15, 2003; 23(10): 3972 - 3980. [Full Text] [PDF]

				G. Yang, J. M. T. Huard, A. J. Beitz, M. E. Ross, and C. Iadecola Stellate Neurons Mediate Functional Hyperemia in the Cerebellar Molecular Layer J. Neurosci., September 15, 2000; 20(18): 6968 - 6973. [Abstract] [Full Text] [PDF]

				K. Niwa, E. Araki, S. G. Morham, M. E. Ross, and C. Iadecola Cyclooxygenase-2 Contributes to Functional Hyperemia in Whisker-Barrel Cortex J. Neurosci., January 15, 2000; 20(2): 763 - 770. [Abstract] [Full Text] [PDF]

				G. Yang, G. Chen, T. J. Ebner, and C. Iadecola Nitric oxide is the predominant mediator of cerebellar hyperemia during somatosensory activation in rats Am J Physiol Regulatory Integrative Comp Physiol, December 1, 1999; 277(6): R1760 - R1770. [Abstract] [Full Text] [PDF]

				U. Lindauer, D. Megow, H. Matsuda, and U. Dirnagl Nitric oxide: a modulator, but not a mediator, of neurovascular coupling in rat somatosensory cortex Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H799 - H811. [Abstract] [Full Text] [PDF]

				G. Yang, R. M. Feddersen, F. Zhang, H. B. Clark, A. J. Beitz, and C. Iadecola Cerebellar vascular and synaptic responses in normal mice and in transgenics with Purkinje cell dysfunction Am J Physiol Regulatory Integrative Comp Physiol, February 1, 1998; 274(2): R529 - R540. [Abstract] [Full Text] [PDF]

				G. Yang, C. Iadecola, and F. M. Faraci Activation of Cerebellar Climbing Fibers Increases Cerebellar Blood Flow : Role of Glutamate Receptors, Nitric Oxide, and cGMP • Editorial Comment: Role of Glutamate Receptors, Nitric Oxide, and cGMP Stroke, February 1, 1998; 29(2): 499 - 508. [Abstract] [Full Text] [PDF]

				C. Iadecola, G. Yang, T. J. Ebner, and G. Chen Local and Propagated Vascular Responses Evoked by Focal Synaptic Activity in Cerebellar Cortex J Neurophysiol, August 1, 1997; 78(2): 651 - 659. [Abstract] [Full Text] [PDF]