Reactome | Activation of NMDA receptors and postsynaptic events

Activation of NMDA receptors and postsynaptic events

Stable Identifier

R-HSA-442755

DOI

10.3180/R-HSA-442755.4

Type

Pathway

Species

Homo sapiens

Compartment

extracellular region, plasma membrane, cytosol, nucleoplasm

ReviewStatus

5/5

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Activation of NMDA receptors and postsynaptic events

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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
23686171	NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease Zhou, Q, Paoletti, P, Bellone, C	Nat. Rev. Neurosci.	2013
20716669	Glutamate receptor ion channels: structure, regulation, and function Myers, SJ, Dingledine, R, Ogden, KK, Wollmuth, LP, Menniti, FS, Hansen, KB, Vance, KM, Yuan, H, Traynelis, SF, McBain, CJ	Pharmacol. Rev.	2010
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