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This Article Full Text Full Text (PDF) Supplemental Results and Figures All Versions of this Article: 98/5/2550    most recent 00376.2007v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Crepel, F. Articles by Daniel, H. Search for Related Content PubMed PubMed Citation Articles by Crepel, F. Articles by Daniel, H.

Developmental Changes in Agonist-Induced Retrograde Signaling at Parallel Fiber–Purkinje Cell Synapses: Role of Calcium-Induced Calcium Release

Pharmacologie de la Synapse, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Université Paris-Sud, Orsay Cedex, France

Submitted 2 April 2007; accepted in final form 7 September 2007

In cerebellar Purkinje cells (PCs), activation of postsynaptic mGluR1 receptors inhibits parallel fiber (PF) to PC synaptic transmission by retrograde signaling. However, results were conflicting with respect to whether endocannabinoids or glutamate (Glu) is the retrograde messenger involved. Experiments in cerebellar slices from 10- to 12-day-old rats and mice confirmed that suppression of PF-excitatory postsynaptic currents (EPSCs) by mGluR1 agonists was entirely blocked by cannabinoid receptor antagonists at this early developmental stage. In contrast, suppression of PF-EPSCs by mGluR1 agonists was only partly blocked by cannabinoid receptor antagonists in 18- to 22-day-old rats, and the remaining suppression was accompanied by an increase in paired-pulse facilitation. This endocannnabinoidindependent suppression of PF-EPSCs was potentiated by the Glu uptake inhibitor D-threo--benzyloxyaspartate (D-TBOA) and blocked by the desensitizing kainate (KA) receptors agonist SYM 2081, by nonsaturating concentrations of 6-cyano-7-nitroquinoxaline-2-3-dione (CNQX) [but not by GYKI 52466 hydrochloride (GYKI)] and by dialyzing PCs with guanosine 5'-[-thio]diphosphate (GDP-S). An endocannnabinoid-independent suppression of PF-EPSCs was also present in nearly mature wild-type mice but was absent in GluR6^–/– mice. The endocannnabinoid-independent suppression of PF-EPSCs induced by mGluR1 agonists and the KA-dependent component of depolarization-induced suppression of excitation (DSE) were blocked by ryanodine acting at a presynaptic level. We conclude that retrograde release of Glu by PCs participates in mGluR1 agonist-induced suppression of PF-EPSCs at nearly mature PF-PC synapses and that Glu operates through activation of presynaptic KA receptors located on PFs and prolonged release of calcium from presynaptic internal calcium stores.