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This Article Full Text Full Text (PDF) All Versions of this Article: 101/6/3089    most recent 91190.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mapelli, L. Articles by D'Angelo, E. PubMed PubMed Citation Articles by Mapelli, L. Articles by D'Angelo, E.

Tonic Activation of GABA_B Receptors Reduces Release Probability at Inhibitory Connections in the Cerebellar Glomerulus

¹Department of Physiology and National Consortium for the Physics of Matter, University of Pavia, Pavia; ²Italian Institute of Technology, Genoa, Italy; and ³Department of Biomolecular Sciences and Biotechnology, University of Milan, Milan, Italy

Submitted 7 November 2008; accepted in final form 26 March 2009

In the cerebellum, granule cells are inhibited by Golgi cells through GABAergic synapses generating complex responses involving both phasic neurotransmitter release and the establishment of ambient -aminobutyric acid (GABA) levels. Although at this synapse the mechanisms of postsynaptic integration have been clarified to a considerable extent, the mechanisms of neurotransmitter release remained largely unknown. Here we have investigated the quantal properties of release during repetitive neurotransmission, revealing that tonic GABA_B receptor activation by ambient GABA regulates release probability. Blocking GABA_B receptors with CGP55845 enhanced the first inhibitory postsynaptic current (IPSC) and short-term depression in a train while reducing trial-to-trial variability and failures. The changes caused by CGP55845 were similar to those caused by increasing extracellular Ca²⁺ concentration, in agreement with a presynaptic GABA_B receptor modulation of release probability. However, the slow tail following IPSC peak demonstrated a remarkable temporal summation and was not modified by CGP55845 or extracellular Ca²⁺ increase. This result shows that tonic activation of presynaptic GABA_B receptors by ambient GABA selectively regulates the onset of inhibition bearing potential consequences for the dynamic regulation of signal transmission through the mossy fiber–granule cell pathway of the cerebellum.