We showed previously that the induction of neural crest (NC) and neural tube (NT) defects is a general property of N-methyl-D-aspartate receptor (NMDAR) antagonists. Since homocysteine induces NC and NT defects and can also act as an NMDAR antagonist, we hypothesized that the mechanism of homocysteine-induced developmental defects is mediated by competitive inhibition of the NMDAR by homocystei...

Long-term potentiation of NMDA-receptor-mediated synaptic transmission (NMDAR-LTP) is a little-understood form of plasticity. In the present study, we investigated whether NMDAR-LTP in the dentate gyrus involves recruitment of extrasynaptic NMDARs, because NMDARs are expressed both synaptically and extrasynaptically with evidence for subtype differences at different locations. We show that befo...

NMDA receptor-dependent long-term depression (NMDAR-LTD) is a form of synaptic plasticity leading to long-lasting decreases in synaptic strength. NMDAR-LTD is essential for spatial and working memory, but its role in hippocampus-dependent fear memory has yet to be determined. Induction of NMDAR-LTD requires the activation of caspase-3 by cytochrome c. Cytochrome c normally resides in mitochondr...

During cortical development, when NR2B subunit is the major component of the NMDA glutamate receptors (NMDARs), moderate NMDAR activity supports neuronal survival at least in part by regulating gene transcription. We report that, in cultured cortical neurons from newborn rats, the NMDARs activated the calcium-responsive transcription regulator nuclear factor of activated T cells (NFAT). Moreove...

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The pathophysiology of perinatal brain injury is multifactorial and involves hypoxia-ischemia (HI) and inflammation. N-methyl-d-aspartate receptors (NMDAR) are present on neurons and glia in immature rodents, and NMDAR antagonists are protective in HI models. To enhance clinical translation of rodent data, we examined protein expression of 6 NMDAR subunits in postmortem human brains without inj...

The σ-1 receptor (Sig1R) is widely expressed in the CNS, where it has a neuroprotective role in ischemia and stroke and an involvement in schizophrenia. The Sig1R interacts functionally with a variety of ion channels, including the NMDA receptor (NMDAR). Here, we used atomic force microscopy (AFM) imaging to investigate the interaction between the Sig1R and the NMDAR. The Sig1R bound directly t...

Glutamate is probably the most important excitatory neurotransmitter in the brain. The glutamate N-methyl-D-aspartate receptor (NMDAR) is a calcium-gated channel that coordinates with G protein-coupled receptors (GPCRs) to establish the efficiency of the synaptic transmission. Cross-regulation between these receptors requires the concerted activity of the histidine triad nucleotide-binding prot...

Glutamate is the main excitatory neurotransmitter of the CNS. Tissue-type plasminogen activator (tPA) is recognized as a modulator of glutamatergic neurotransmission. This attribute is exemplified by its ability to potentiate calcium signaling following activation of the glutamate-binding NMDA receptor (NMDAR). It has been hypothesized that tPA can directly cleave the NR1 subunit of the NMDAR a...

Long-term depression (LTD) is a long-lasting activity-dependent decrease in synaptic strength. NMDA receptor (NMDAR)-dependent LTD, an extensively studied form of LTD, involves the endocytosis of AMPA receptors (AMPARs) via protein dephosphorylation, but the underlying mechanism has remained unclear. We show here that a regulated interaction of the endocytic adaptor RalBP1 with two synaptic pro...