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 gamma-aminobutyric acid (GABA) tone on local increases in cerebellar metabolic rate of oxygen (CeMR(O(2))) 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 CeMR(O(2)) under control conditions. Topical application of the GABA(A) receptor agonist muscimol blocked the increase in CeMR(O(2)) evoked by synaptic excitation concomitant with attenuation of cerebellar blood flow (CeBF) responses. The effect was reversed by the GABA(A) 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 CeMR(O(2)). The findings are consistent with the hypothesis that activity-dependent rises in CeBF and CeMR(O(2)) are controlled by a common feed-forward pathway and provide evidence for modification of cerebral blood flow and CMR(O(2)) by GABA.