Activation of NMDA receptors and postsynaptic events

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R-HSA-442755
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Pathway
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Homo sapiens
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NMDA receptors are a subtype of ionotropic glutamate receptors that are specifically activated by a glutamate agonist N-methyl-D-aspartate (NMDA). Activation of NMDA receptors involves opening of the ion channel that allows the influx of Ca2+. NMDA receptors are central to activity dependent changes in synaptic strength and are predominantly involved in the synaptic plasticity that pertains to learning and memory. A unique feature of NMDA receptors, unlike other glutamate receptors, is the requirement for dual activation, both voltage-dependent and ligand-dependent activation. The ligand-dependent activation of NMDA receptors requires co-activation by two ligands, glutamate and glycine. However, at resting membrane potential, the pore of ligand-bound NMDA receptors is blocked by Mg2+. The voltage dependent Mg2+ block is relieved upon depolarization of the post-synaptic membrane. NMDA receptors are coincidence detectors, and are activated only if there is a simultaneous activation of both pre- and post-synaptic cell. Upon activation, NMDA receptors allow the influx of Ca2+ that initiates various molecular signaling cascades involved in the processes of learning and memory. For review, please refer to Cohen and Greenberg 2008, Hardingham and Bading 2010, Traynelis et al. 2010, and Paoletti et al. 2013.

Literature References
PubMed ID Title Journal Year
18616423 Communication between the synapse and the nucleus in neuronal development, plasticity, and disease

Cohen, S, Greenberg, ME

Annu Rev Cell Dev Biol 2008
20842175 Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders

Hardingham, GE, Bading, H

Nat. Rev. Neurosci. 2010
20716669 Glutamate receptor ion channels: structure, regulation, and function

Traynelis, SF, Wollmuth, LP, McBain, CJ, Menniti, FS, Vance, KM, Ogden, KK, Hansen, KB, Yuan, H, Myers, SJ, Dingledine, R

Pharmacol. Rev. 2010
23686171 NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease

Paoletti, P, Bellone, C, Zhou, Q

Nat. Rev. Neurosci. 2013
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