title: Regulation of NMDA receptor Ca2+ signalling and synaptic plasticity.
abstract: NMDARs (N-methyl-D-aspartate receptors) are critical for synaptic function throughout the CNS (central nervous system). NMDAR-mediated Ca(2+) influx is implicated in neuronal differentiation, neuronal migration, synaptogenesis, structural remodelling, long-lasting forms of synaptic plasticity and higher cognitive functions. NMDAR-mediated Ca(2+) signalling in dendritic spines is not static, but can be remodelled in a cell- and synapse-specific manner by NMDAR subunit composition, protein kinases and neuronal activity during development and in response to sensory experience. Recent evidence indicates that Ca(2+) permeability of neuronal NMDARs, NMDAR-mediated Ca(2+) signalling in spines and induction of NMDAR-dependent LTP (long-term potentiation) at hippocampal Schaffer collateral-CA1 synapses are under control of the cAMP/PKA (protein kinase A) signalling cascade. Thus, by enhancing Ca(2+) influx through NMDARs in spines, PKA can regulate the induction of LTP. An emerging concept is that activity-dependent regulation of NMDAR-mediated Ca(2+) signalling by PKA and by extracellular signals that modulate cAMP or protein phosphatases at synaptic sites provides a dynamic and potentially powerful mechanism for bi-directional regulation of synaptic efficacy and remodelling.
authors.affiliation: Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: C Geoffrey
authors.initials: CG
authors.lastname: Lau
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Alma
authors.initials: A
authors.lastname: Rodenas-Ruano
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takayasu
authors.forename: Jessica
authors.initials: J
authors.lastname: Murphy
authors.forename: Michael V L
authors.initials: MV
authors.lastname: Bennett
authors.forename: R Suzanne
authors.initials: RS
authors.lastname: Zukin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D016194:Receptors, N-Methyl-D-Aspartate; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium