Postsynaptic Signaling and Plasticity Mechanisms

Sheng, Morgan; Kim, Myung Jong

doi:10.1126/science.1075333

Cited by 658 publications

(521 citation statements)

References 86 publications

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“…In the CNS, NMDAR-mediated signals are critical for the survival of developing neurons and for several forms of synaptic plasticity and learning and memory (Sheng and Kim, 2002). Conversely, NMDAR-mediated excitotoxicity has been implicated in a diversity of neurodegenerative disorders.…”

Section: Discussionmentioning

confidence: 99%

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

Qian

He²,

Hu³

et al. 2007

J. Neurosci.

144

103

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Fleeting activation of NMDA receptors (NMDARs) induces long-term modification of synaptic connections and refinement of neuronal circuits, which may underlie learning and memory and contribute to pathogenesis of a diversity of neurological diseases, including epilepsy. Here, we found that NR2A and NR2B subunit-containing NMDARs were coupled to distinct intracellular signaling, resulting in differential BDNF expression and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Selective activation of NR2A-containing NMDARs increased BDNF gene expression. Activation of NR2B-containing NMDARs led to ERK1/2 phosphorylation. Furthermore, selectively blocking NR2A-containing NMDARs impaired epileptogenesis and the development of mossy fiber sprouting in the kindling and pilocarpine rat models of limbic epilepsy, whereas inhibiting NR2B-containing NMDARs had no effects in epileptogenesis and mossy fiber sprouting. Interestingly, blocking either NR2A- or NR2B-containing NMDARs decreased status epilepticus-induced neuronal cell death. The specific requirement of NR2A and its downstream signaling for epileptogenesis implicates attractive new targets for the development of drugs that prevent epilepsy in patients with brain injury.

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Section: Discussionmentioning

confidence: 99%

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

Qian

He²,

Hu³

et al. 2007

J. Neurosci.

144

103

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show abstract

“…The major postsynaptic glutamate receptors include the N-methyl-D-aspartate receptor (NMDAR), the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR), and the group I metabotropic glutamate receptor (mGluR). It has been reported that PSD-70 as Src, a member of the Src family in the central nervous system (CNS), which plays important roles in the synaptic targeting and signaling of NMDARs [4,5] . However, the mechanisms remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Knock-down of postsynaptic density protein 95 expression by antisense oligonucleotides protects against apoptosis-like cell death induced by oxygen-glucose deprivation in vitro

et al. 2012

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“…Postsynaptic density (PSD) proteins are necessary for excitatory glutamatergic postsynaptic responses, and include scaffolding and functional elements that modulate/mediate signal transduction and trafficking of synaptic proteins (reviewed by Sheng and Kim, 2002;Wenthold et al, 2003;Bredt and Nicoll, 2003;Ehrengruber et al, 2004). In addition to glutamate receptors (GluRs) such as α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) and Nmethyl-D-aspartate (NMDA) receptors, numerous other proteins associate with GluRs in the postsynaptic membrane and PSD.…”

Section: Introductionmentioning

confidence: 99%

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Petralia

Sans

Wang

et al. 2005

Molecular and Cellular Neuroscience

209

196

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In glutamatergic synapses, glutamate receptors (GluRs) associate with many other proteins involved in scaffolding and signal transduction. The ontogeny of these postsynaptic density (PSD) proteins involves changes in their composition during development, paralleling changes in GluR type and function. In the CA1 region of the hippocampus, at postnatal day 2 (P2), many synapses already have a distinct PSD. We used immunoblot analysis, subcellular fractionation, and quantitative immunogold electron microscopy to examine the distribution of PSD proteins during development of the hippocampus. Synapses at P2 contained substantial levels of NR1 and NR2B and most GluRassociated proteins, including SAP102, SynGAP, the chain of proteins from GluRs/SAP102 through GKAP/Shank/Homer and metabotropic glutamate receptors, and the adhesion factors, cadherin, catenin, neuroligin, and Nr-CAM. Development was marked by substantial decreases in NR2B and SAP102 and increases in NR2A, PSD-95, AMPA receptors and CaMKII. Other components showed more moderate changes.

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Postsynaptic Signaling and Plasticity Mechanisms

Cited by 658 publications

References 86 publications

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

Knock-down of postsynaptic density protein 95 expression by antisense oligonucleotides protects against apoptosis-like cell death induced by oxygen-glucose deprivation in vitro

Ontogeny of postsynaptic density proteins at glutamatergic synapses

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