Golgi Cell-Mediated Activation of Postsynaptic GABAB Receptors Induces Disinhibition of the Golgi Cell-Granule Cell Synapse in Rat Cerebellum

Abstract

In the cerebellar glomerulus, GABAergic synapses formed by Golgi cells regulate excitatory transmission from mossy fibers to granule cells through feed-forward and feedback mechanisms. In acute cerebellar slices, we found that stimulating Golgi cell axons with a train of 10 impulses at 100 Hz transiently inhibited both the phasic and the tonic components of inhibitory responses recorded in granule cells. This effect was blocked by the GABAB receptor blocker CGP35348, and could be mimicked by bath-application of baclofen (30 µM). This depression of IPSCs was prevented when granule cells were dialyzed with GDPβS. Furthermore, when synaptic transmission was blocked, GABAA currents induced in granule cells by localized muscimol application were inhibited by the GABAB receptor agonist baclofen. These findings indicate that postsynaptic GABAB receptors are primarily responsible for the depression of IPSCs. This inhibition of inhibitory events results in an unexpected excitatory action by Golgi cells on granule cell targets. The reduction of Golgi cell-mediated inhibition in the cerebellar glomerulus may represent a regulatory mechanism to shift the balance between excitation and inhibition in the glomerulus during cerebellar information processing.