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Neuroscience: CNS disease, pain, brain research, ion channels, synaptic transmission, channelopathies, neuronal network
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[Review] Presynaptic NMDA receptors: Are they dendritic receptors in disguise?

[Review] Presynaptic NMDA receptors: Are they dendritic receptors in disguise? | Neuroscience_topics | Scoop.it

The N-methyl-d-aspartate (NMDA) receptor plays an essential role in excitatory transmission, synaptic integration, and learning and memory. In the classical view, postsynaptic NMDA receptors act as canonical coincidence detectors providing a ‘molecular switch’ for the induction of various forms of short- and long-term synaptic plasticity. Over the past twenty years there has been accumulating evidence to suggest that NMDA receptors are also expressed presynaptically and are involved in the regulation of synaptic transmission and specific forms of activity-dependent plasticity in developing neural circuits. However, the existence of presynaptic NMDA receptors remains a contentious issue. In this review, I will discuss the criteria required for identifying functional presynaptic receptors, novel methods for probing NMDA receptor function, and recent evidence to suggest that NMDA receptors are expressed at presynaptic sites in a target-specific manner. (...) - by Duguid ICBrain Research BulletinVolume 93, April 2013, Pages 4–9

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Metabotropic NMDA receptor function is required for β-amyloid–induced synaptic depression

The mechanisms by which β-amyloid (Aβ), a peptide fragment believed to contribute to Alzheimer’s disease, leads to synaptic deficits are not known. Here we find that elevated oligomeric Aβ requires ion flux-independent function of NMDA receptors (NMDARs) to produce synaptic depression. Aβ activates this metabotropic NMDAR function on GluN2B-containing NMDARs but not on those containing GluN2A. Furthermore, oligomeric Aβ leads to a selective loss of synaptic GluN2B responses, effecting a switch in subunit composition from GluN2B to GluN2A, a process normally observed during development. Our results suggest that conformational changes of the NMDAR, and not ion flow through its channel, are required for Aβ to produce synaptic depression and a switch in NMDAR composition. This Aβ-induced signaling mediated by alterations in GluN2B conformation may be a target for therapeutic intervention of Alzheimer’s disease. (...) - by Kessels HW et al.PNASMarch 5, 2013 vol. 110 no. 104033-4038

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Metabotropic NMDA receptor function is required for NMDA receptor-dependent long-term depression

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 Ca2+ entry through NMDARs triggers LTP; lower Ca2+ entry triggers LTD. Here we show that ligand binding to NMDARs is sufficient to induce LTD; neither ion flow through NMDARs nor Ca2+ rise is required. However, basal levels of Ca2+ are permissively required. Lowering, but not maintaining, basal Ca2+levels with Ca2+ chelators blocks LTD and drives strong synaptic potentiation, indicating that basal Ca2+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. (...) - by Nabavi S. et al.PNAS 2013 110 (10) 4027-4032

Julien Hering, PhD's insight:

A great article from R. Malinov's team about fine mechanisms controlling synaptic plasticity through levels of calcium 

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