The Journal of Neurophysiology Vol. 84 No. 4 October 2000, pp. 2016-2025
Copyright ©2000 by the American Physiological Society

-Adrenergic Receptor-Mediated Presynaptic Facilitation of Inhibitory GABAergic Transmission at Cerebellar Interneuron-Purkinje Cell Synapses

Laboratory of Molecular Neurobiology, Mitsubishi Kasei Institute of Life Sciences and CREST, JST (Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation), Tokyo 194-8511, Japan

Saitow, Fumihito, Shin'Ichiro Satake, Junko Yamada, and Shiro Konishi. -Adrenergic Receptor-Mediated Presynaptic Facilitation of Inhibitory GABAergic Transmission at Cerebellar Interneuron-Purkinje Cell Synapses. J. Neurophysiol. 84: 2016-2025, 2000. Norepinephrine (NE) has been shown to elicit long-term facilitation of GABAergic transmission to rat cerebellar Purkinje cells (PCs) through -adrenergic receptor activation. To further examine the locus and adrenoceptor subtypes involved in the NE-induced facilitation of GABAergic transmission, we recorded inhibitory postsynaptic currents (IPSCs) evoked by focal stimulation with paired-pulse (PP) stimuli from PCs in rat cerebellar slices by whole cell recordings and analyzed the PP ratio of the IPSC amplitude. NE increased the IPSC amplitude with a decease in the variance of the PP ratio, which was mimicked by presynaptic manipulation of the transmission caused by increasing the extracellular Ca²⁺ concentration, confirming that the presynaptic adrenergic receptors are responsible for the facilitation. Pharmacological tests showed that the ₂-adrenoceptor antagonist, ICI118,551, but not the ₁-adrenoceptor antagonist, CGP20712A, blocked the NE-induced IPSC facilitation, suggesting that the ₂-adrenoceptors on cerebellar interneurons, basket cells (BCs), mediate the noradrenergic facilitation of GABAergic transmission. Double recordings were performed from BCs and PCs to further characterize the regulation of the GABAergic synapses. First, on-cell recordings from BCs showed that the -agonist isoproterenol (ISP) increased the frequencies of the spontaneous spikes in BCs and the spike-triggered IPSCs in PCs recorded with the whole cell mode. The amplitude of the spike-triggered IPSCs decreased or increased depending on the individual GABAergic synapses examined. Forskolin invariably increased both the amplitude and the frequency of the spike-triggered IPSCs. Double whole cell recordings from BC-PC pairs showed that ISP mainly caused an increase in the 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 cerebellar cortex is mediated, at least in part, by depolarization and action potential discharges in the BCs through activation of the ₂-adrenoceptors in BCs coupled to intracellular cyclic AMP formation.