The excitatory neurotransmitter glutamate plays important roles in the mammalian brain, ranging from synaptic plasticity to memory. To mediate these functions, glutamate activates two types of receptors: ligand-gated channels and metabotropic receptors coupled to G-proteins. Both families of glutamate receptors share no sequence homology and possess original structural features compared with ot...

Introduction Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. There are multiple receptors for glutamate: in addition to the fast transfer of information via the recently cloned receptors for AMPA [(RS)-y-amino-3hydroxy5 -methyl-4-isoxazolepropionate]/kainate [ l ] and the high-affinity kainate receptor [2], Ca+ influx via the post-synaptic N-methyl-i>...

The glutamate excitotoxicity hypothesis of ischemic cell damage holds that cell damage caused by transient cerebral ischemia is triggered by glutamate, released during ischemia from the intracellular compartment into the synaptic cleft: high extracellular glutamate levels activate ionotropic glutamate receptors, thus inducing an overflow of calcium ions into the neurones and a calcium-induced a...

the protective effect of a l-type calcium channel blocker, nimodipine, on cell injury induced by oxygen-glucose deprivation (ogd) in pc12 cells was investigated. pc12 cells were exposed to in-vitro oxygen-glucose deprivation (30 minutes and 60 minutes respectively) in the presence or absence of nimodipine (10mm/l) in three different time schedules (pre-24h, pre-3h and concurrently). cellular vi...

Excitatory postsynaptic currents in the CA1 region of rat hippocampal slices are mediated primarily by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in response to synaptically released glutamate. Outside-out patches from pyramidal cells in this region have shown that AMPA receptors are desensitized by short (1 ms) pulses of glutamate. We have taken a number of appro...

Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS) and is a major player in complex brain functions. Glutamatergic transmission is primarily mediated by ionotropic glutamate receptors, which include NMDA, AMPA and kainate receptors. However, glutamate exerts modulatory actions through a family of metabotropic G-protein-coupled glutamate receptors (mGluRs). Dys...

Glutamate receptors are promising drug targets for the treatment of urgent suicide ideation and chronic major depressive disorder (MDD) that may lead to suicide completion. Antagonists of glutamatergic NMDA receptors reduce depressive symptoms faster than traditional antidepressants, with beneficial effects occurring within hours. Glutamate is the prominent excitatory input to the noradrenergic...

The objective of the present study was to determine if a neuron that expresses multiple glutamate receptors targets the same receptors to all glutamatergic postsynaptic populations, or if the receptors are differentially targeted to specific postsynaptic populations. As a model for this study, we chose the fusiform cell of the dorsal cochlear nucleus. This neuron expresses multiple glutamate re...

Ionotropic glutamate receptors are postsynaptic tetrameric ligand-gated channels whose activity mediates fast excitatory transmission. Glutamate binding to clamshell-shaped ligand binding domains (LBDs) triggers opening of the integral ion channel, but how the four LBDs orchestrate receptor activation is unknown. Here, we present a high-resolution x-ray crystal structure displaying two tetramer...

A specific set of molecules including glutamate receptors is targeted to the postsynaptic specialization of excitatory synapses in the brain, gathering in a structure known as the postsynaptic density (PSD). Synaptic targeting of glutamate receptors depends on interactions between the C-terminal tails of receptor subunits and specific PDZ domain-containing scaffold proteins in the PSD. These sc...