Gamma-aminobutyric acid modulates local brain oxygen consumption and blood flow in rat cerebellar cortex

Abstract

In the awake brain, the global metabolic rate of oxygen consumption is largely constant, while variations exist between regions dependent on the ongoing activity. This suggests that control mechanisms related to activity, that is, neuronal signaling, may redistribute metabolism in favor of active networks. This study examined the influence of γ-aminobutyric acid (GABA) tone on local increases in cerebellar metabolic rate of oxygen (CeMR O2) evoked by stimulation of the excitatory, glutamatergic climbing fiber-Purkinje cell synapse in rat cerebellum. In this network, the postsynaptic depolarization produced by synaptic excitation is preserved despite variations in GABAergic tone. Climbing fiber stimulation induced frequency-dependent increases in synaptic activity and CeMRO2 under control conditions. Topical application of the GABAA receptor agonist muscimol blocked the increase in CeMRO2 evoked by synaptic excitation concomitant with attenuation of cerebellar blood flow (CeBF) responses. The effect was reversed by the GABAA receptor antagonist bicuculline, which also reversed the effect of muscimol on synaptic activity and CeBF. Climbing fiber stimulation during bicuculline application alone produced a delayed undershoot in CeBF concomitant with a prolonged rise in CeMRO2. The findings are consistent with the hypothesis that activity-dependent rises in CeBF and CeMRO2 are controlled by a common feed-forward pathway and provide evidence for modification of cerebral blood flow and CMRO2 by GABA. © 2008 ISCBFM All rights reserved.