title: Role of p/q-Ca2+ channels in metabotropic glutamate receptor 2/3-dependent presynaptic long-term depression at nucleus accumbens synapses.
abstract: The nucleus accumbens (NAc) is an important cerebral area involved in reward and spatial memory (Pennartz et al., 1994), but little is known about synaptic plasticity in this region. Here, electron microscopy revealed that, in the NAc, metabotropic glutamate receptors 2/3 (mGlu2/3) immunostaining was essentially associated with axonal terminals and glial processes, whereas postsynaptic dendrites and neuronal cell bodies were unstained. Electrophysiological techniques in the NAc slice preparation demonstrated that activation of mGlu2/3 with synaptically released glutamate or specific exogenous agonist, such as LY354740 (200 nm, 10 min), induced long-term depression of excitatory synaptic transmission (mGlu2/3-LTD). Tetanic-LTD and pharmacological mGlu2/3-LTD occluded each other, suggesting common mechanisms. The mGlu2/3-LTD did not require synaptic activity but depended on the cAMP-protein kinase A cascade. Selective inhibition of P/Q-type Ca(2+) channels with omega-agatoxin-IVA occluded the expression of mGlu2/3-LTD, and, conversely, the inhibitory effects of omega-agatoxin-IVA were abolished during mGlu2/3-LTD. Thus, mGlu2/3 play an important role in the control of use-dependent synaptic plasticity at prelimbic cortex-NAc synapses: their activation causes a form of LTD mediated by the long-lasting reduction of P/Q-type Ca(2+)channels contribution to transmitter release.
authors.affiliation: Centre National de la Recherche Scientifique Unité Propre de Recherche 9023, Unité Mixte de Recherche 5101, and Unité Propre de Recherche 1142, 34094 Montpellier Cedex 05, France.
authors.forename: David
authors.initials: D
authors.lastname: Robbe
authors.forename: Gerard
authors.initials: G
authors.lastname: Alonso
authors.forename: Severine
authors.initials: S
authors.lastname: Chaumont
authors.forename: Joel
authors.initials: J
authors.lastname: Bockaert
authors.forename: Olivier J
authors.initials: OJ
authors.lastname: Manzoni
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020865:Calcium Channels, P-Type / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D017868:Cyclic AMP-Dependent Protein Kinases; C104753:eglumetad; D002118:Calcium