In the 1990s there was intense interest in ionotropic glutamate receptors as therapeutic targets for diverse neurological disorders, including epilepsy. NMDA receptors were thought to play a key role in the generation of seizures, leading to clinical studies of NMDA receptor blocking drugs in epilepsy. Disappointing results dampened enthusiasm for ionotropic glutamate receptors as a therapeutic...

Glutamate transporters (GluTs) prevent the accumulation of glutamate and influence the occupancy of receptors at synapses. The ability of extrasynaptic NMDA receptors and metabotropic glutamate receptors to participate in signaling is tightly regulated by GluT activity. Astrocytes express the highest density of GluTs and dominate clearance away from these receptors; synapses that are not associ...

Ischemic injury of immature oligodendrocytes is a major component of the brain injury associated with cerebral palsy, the most common human birth disorder. We now report that cultured immature oligodendrocytes [O4(+)/galactoceramide (GC)(-)] are exquisitely sensitive to ischemic injury (80% of cells were dead after 25.5 min of oxygen and glucose withdrawal). This rapid ischemic cell death was m...

The NMDA type of ligand-gated glutamate receptor requires the presence of both glutamate and glycine for gating. These receptors are hetero-oligomers of NR1 and NR2 subunits. Previously it was thought that the binding sites for glycine and glutamate were formed by residues on the NR1 subunit. Indeed, it has been shown that the effects of glycine are controlled by residues on the NR1 subunit, an...

Under standard conditions, cultured ventral spinal neurons cluster AMPA- but not NMDA-type glutamate receptors at excitatory synapses on their dendritic shafts in spite of abundant expression of the ubiquitous NMDA receptor subunit NR1. We demonstrate here that the NMDA receptor subunits NR2A and NR2B are not routinely expressed in cultured spinal neurons and that transfection with NR2A or NR2B...

It is widely held that the soma and basal dendrites of olfactory bulb mitral cells receive exclusively inhibitory synaptic input from local interneurons. However, the mitral somatodendritic membrane exhibits immunoreactivity for a variety of glutamate receptors, and blocking GABA receptors unmasks mitral cell self-excitation. This excitation is proposed to be mediated either by diffuse spillove...

McNearney TA, Ma Y, Chen Y, Taglialatela G, Yin H, Zhang W, Westlund KN. A peripheral neuroimmune link: glutamate agonists upregulate NMDA NR1 receptor mRNA and protein, vimentin, TNF, and RANTES in cultured human synoviocytes. Am J Physiol Regul Integr Comp Physiol 298: R584–R598, 2010. First published December 9, 2009; doi:10.1152/ajpregu.00452.2009.—Human primary and clonal synovial cells we...

Previous studies have shown that blockade of ventral tegmental area (VTA) glutamate N-Methyl-D-Aspartate (NMDA) receptors induces reward, stimulates forward locomotion and enhances brain stimulation reward. Glutamate induces two types of excitatory response on VTA neurons, a fast and short lasting depolarization mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors and ...

With key roles in essential brain functions ranging from the basics of excitatory neurotransmission to the complexities of learning and memory, the N-methyl-D-aspartate (NMDA) receptor can be considered one of the fundamental neurotransmitter receptors in the brain. Named for its most potent exogenous agonist, the NMDA receptor has been thoroughly characterized via electrophysiological and phar...

We have used site-directed mutagenesis of amino acids located within the S1 and S2 ligand binding domains of the NR2A N-methyl-D-aspartate (NMDA) receptor subunit to explore the nature of ligand binding. Wild-type or mutated NR1/NR2A NMDA receptors were expressed in Xenopus laevis oocytes and studied using two electrode voltage clamp. We investigated the effects of mutations in the S1 and S2 re...