Synaptic plasticity at excitatory synapses in the brain is largely achieved by rapid changes in the number of synaptic -amino3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptors. Stargazin, a membrane protein that interacts with AMPA receptors, is believed to play a pivotal role in trafficking AMPA receptors to the plasma membrane and targeting them to the synapse. However, it is unclear ...

Glutamate is the major excitatory amino acid neurotransmitter in the CNS, including the neocortex, hippocampus, and spinal cord. Normal synaptic transmission is mainly mediated by glutamate AMPA and/or kainate receptors. Glutamate N-methyl-D-aspartate (NMDA) receptors are normally inactive and only activated when a sufficient postsynaptic depolarization is induced by the activity. Here we show ...

Quisqualate, a glutamate analogue, displaced L-[3H]glutamate binding in a biphasic manner, corresponding to "high-affinity" and "low-affinity" binding sites. High-affinity quisqualate sites were termed "quisqualate-sensitive L-[3H]glutamate" binding sites. Quisqualate-sensitive L-[3H]glutamate binding was regionally distributed, with the highest levels present in the cerebellar molecular layer....

In this paper, we report a study on some new 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylate derivatives (TQXs), bearing a nitrogen-containing heterocycle at position-9, and designed as (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptor antagonists. These compounds ensue from the structural modification of previously reported 8-heteroaryl-TQXs which...

AMPA and NMDA receptor channels are closely related molecules, yet they respond to glutamate with distinct kinetics, attributable to differences in ligand binding and channel gating steps (for review, see Edmonds et al., 1995). We used two complementary approaches to investigate the number of functional binding sites on AMPA channels on outside-out patches from cultured hippocampal neurons. The...

We report the crystal structure of the glycosylated ligand-binding (S1S2) domain of the kainate receptor subunit GluR6, in complex with the agonist domoate. The structure shows the expected overall homology with AMPA and NMDA receptor subunit structures but reveals an unexpected binding mode for the side chain of domoate, in which contact is made to the larger lobe only (lobe I). In common with...

The "waist" area (W) of the parabrachial nucleus contains neurons that receive orosensory input and play a role in the initiation of oromotor behaviors. Immunohistochemical data indicate that neurons in W receive glutamatergic input and express glutamate receptors, but a behavioral role for glutamate neurotransmission within W has not been investigated. To determine the role of specific glutama...

During cerebral ischaemia, energetic failure of injured cells together with excessive release of glutamate the most common excitatory amino acid in the brain, lead to excitotoxicity and immediate or delayed neuronal death. There is strong experimental evidence to support the neuroprotective role played by anaesthetic agents. Hence, barbiturates, volatile anesthetics or ketamine exhibit signific...

Estrogen replacement therapy in women is associated with improvement of cognitive deficits and reduced incidence of Alzheimer's disease. The present study indicates that estrogen is neuroprotective against N-methyl-d-aspartate (NMDA)- and kainate-mediated neurotoxicity, an effect mediated by tyrosine kinase/mitogen-activated protein kinase (MAPK) pathways. Estrogen also stimulates tyrosine phos...