Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways

By G. Hardingham, Y. Fukunaga, Hilmar Bading. Nature Neuroscience, 2002

1,731 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience

View Paper: https://www.semanticscholar.org/paper/2e469907f7848bb28a38d775a728d8fa6918975b

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In Cellular and Molecular Neuroscience

Citations in the corpus

Cytokine Targets in the Brain: Impact on Neurotransmitters and Neurocircuits (2013, background): “[7, 75, 76] Of note, release of glutamate by astrocytes is more likely to access extrasynaptic n-methylD-aspartate (NMDA) receptors, which have been shown to lead to decreased brain derived neurotrophic factor, which is important in neurogenesis.[77] Activation of IDO also leads to the production of”
Immune System to Brain Signaling: Neuropsychopharmacological Implications (2011, background): “Of particular concern, excessive release of glutamate by astrocytes can access extrasynaptic NMDA receptors, which mediate excitotoxicity and decreased production of trophic factors including brain derived neurotrophic factor (BDNF) (Hardingham et al., 2002; Haydon and Carmignoto, 2006).”
Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists. (2012, result): “They are, however, in strong disagreement with those obtained in cultured neurons (Hardingham et al., 2002; Hardingham and Bading, 2003; Léveillé et al., 2008) reporting a preferential role for extrasynaptic NMDARs in excitotoxicity.”
Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond (2006, background): “Additionally, the NR2B subunit predominates in extrasynaptic rather than synaptic NMDARs, and it is thought that excessive stimulation of extrasynaptic (NR2B predominant) receptors might contribute to neurotoxicity, whereas physiological synaptic activity (predominantly containing NR2A>NR2B subunits”
A guide to cell death pathways (2023, neutral): “Glutamate is a key excitatory neurotransmitter in the mammalian nervous system that drives Ca 2+ influx into neurons 191 (Fig.”
Soluble Aβ oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors (2011, background): “Although some reports suggest that supraphysiological concentrations of synthetic A can enhance ERK and CREB phosphorylation within minutes (Dineley et al., 2001; Chong et al., 2006), the differences from our time course may relate to our natural sources of soluble A and our low concentrations, as f”
Regulation of NMDA Receptor Subunit Expression and Its Implications for LTD, LTP, and Metaplasticity (2008, background): “Extrasynaptic NMDARs are activated not only at pathological situations (Hardingham et al., 2002), but also by bursts of activity that can occur under physiological situations (Harris and Pettit, 2008).”
Chronic Glutamate Toxicity in Neurodegenerative Diseases—What is the Evidence? (2015, background): “An influential study using primary neuronal cultures (Hardingham et al., 2002) suggested that synaptic and extrasynaptic NMDA receptors have counteracting effects on cell fate with nerve cell death being mainly mediated by extrasynaptic NMDA receptors.”