title: Metabotropic NMDA receptor function is required for NMDA receptor-dependent long-term depression.
abstract: NMDA receptor (NMDAR) activation controls long-term potentiation (LTP) as well as long-term depression (LTD) of synaptic transmission, cellular models of learning and memory. A long-standing view proposes that a high level of Ca(2+) entry through NMDARs triggers LTP; lower Ca(2+) entry triggers LTD. Here we show that ligand binding to NMDARs is sufficient to induce LTD; neither ion flow through NMDARs nor Ca(2+) rise is required. However, basal levels of Ca(2+) are permissively required. Lowering, but not maintaining, basal Ca(2+) levels with Ca(2+) chelators blocks LTD and drives strong synaptic potentiation, indicating that basal Ca(2+) levels control NMDAR-dependent LTD and basal synaptic transmission. Our findings indicate that metabotropic actions of NMDARs can weaken active synapses without raising postsynaptic calcium, thereby revising and expanding the mechanisms controlling synaptic plasticity.
authors: Center for Neural Circuits and Behavior, Division of Biology, Department of Neuroscience and Section of Neurobiology, University of California at San Diego, La Jolla, CA 92093, USA.
authors: Sadegh
authors: S
authors: Nabavi
authors: Helmut W
authors: HW
authors: Kessels
authors: Stephanie
authors: S
authors: Alfonso
authors: Jonathan
authors: J
authors: Aow
authors: Rocky
authors: R
authors: Fox
authors: Roberto
authors: R
authors: Malinow
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D002614:Chelating Agents; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D004533:Egtazic Acid; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C057013:7-chlorokynurenic acid