beta-Adrenergic receptor-mediated presynaptic facilitation of inhibitory GABAergic transmission at cerebellar interneuron-Purkinje cell synapses

Norepinephrine (NE) has been shown to elicit long-term facilitation of GABA ergic transmission to rat cerebellar Purkinje cells (PCs) through beta-adre nergic receptor activation. To further examine the locus and adrenoceptor s ubtypes involved in the NE-induced facilitation of GABAergic transmission, we recorded inhibitory postsynaptic currents (IPSCs) evoked by focal stimul ation with paired-pulse (PP) stimuli from PCs in rat cerebellar slices by w hole cell recordings and analyzed the PP ratio of the IPSC amplitude. NE in creased the IPSC amplitude with a decease in the variance of the PP ratio, which was mimicked by presynaptic manipulation of the transmission caused b y increasing the extracellular Ca2+ concentration, confirming that the pres ynaptic adrenergic receptors are responsible for the facilitation. Pharmaco logical tests showed that the beta(2)-adrenoceptor antagonist, ICI1 18,551, but not the beta(1)-adrenoceptor antagonist, CGP20712A, blocked the NE-ind uced IPSC facilitation, suggesting that the beta(2)-adrenoceptors on cerebe llar interneurons, basket cells (BCs), mediate the noradrenergic facilitati on of GABAergic transmission. Double recordings were performed from BCs and PCs to further characterize the regulation of the GABAergic synapses. Firs t, on-cell recordings from BCs showed that the beta-agonist isoproterenol ( ISP) increased the frequencies of the spontaneous spikes in BCs and the spi ke-triggered IPSCs in PCs recorded with the whole cell mode. The amplitude of the spike-triggered IPSCs decreased or increased depending on the indivi dual GABAergic synapses examined. Forskolin invariably increased both the a mplitude and the frequency of the spike-triggered IPSCs. Double whole cell recordings from BC-PC pairs showed that ISP mainly caused an increase in th e amplitude of the IPSCs evoked in the PCs by an action current in the BCs produced in response to voltage steps from -60 to -10 mV. Our data suggest that the noradrenergic facilitation of GABAergic transmission in the rat ce rebellar cortex is mediated, at least in part, by depolarization and action potential discharges in the BCs through activation of the beta(2)-adrenoce ptors in BCs coupled to intracellular cyclic AMP formation.