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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 102/2/965    most recent 00269.2009v1 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 Crépel, F. PubMed PubMed Citation Articles by Crépel, F.

Role of Presynaptic Kainate Receptors at Parallel Fiber–Purkinje Cell Synapses in Induction of Cerebellar LTD: Interplay With Climbing Fiber Input

Pharmacologie de la Synapse, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Université Paris-Sud and Centre National de la Recherche Scientifique, Orsay Cedex, France

Submitted 25 March 2009; accepted in final form 12 June 2009

Until recently, except for A1 adenosine, N-methyl-D-aspartate, and cannabinoid receptors, little effort has been made to unravel possible roles of parallel fiber (PF) presynaptic receptors in long-term depression (LTD) of synaptic transmission at PF–Purkinje cell (PC) synapses. Presynaptic kainate (KA) receptors are also present on PFs and might also influence LTD induction by modulating glutamate (Glu) release at PF–PC synapses. This hypothesis was tested by comparing the efficacy of two pairing protocols in inducing LTD in adult wild-type and knock-out mice for the Glu receptor 6 (GluR6) subunit of KA receptors. Activation of presynaptic KA receptors was unnecessary for LTD induction when PF inputs were paired with climbing fiber (CF) stimulation but became crucial when CF input was replaced by direct depolarization of PCs. By comparing basal paired-pulse facilitation of PF-excitatory postsynaptic currents (EPSCs) and depolarization-induced suppression of excitation in adult wild-type and GluR6 knock-out mice, it was shown that the participation of PF presynaptic KA receptors in LTD induction was likely to mainly result from their tonic activation by basal extracellular Glu, rather than from their activation by retrograde release of Glu by PCs during pairing protocols. Finally, this study suggests that, in adult mice, CFs not only participate in LTD induction by depolarizing postsynaptic cells but also by activating postsynaptic mGluR1 metabotropic glutamate receptors at CF–PC synapses.