BACKGROUND AND PURPOSE Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor inhibition has been hypothesized to provide neuroprotective efficacy after cerebral ischemia on the basis of the activity in experimental ischemia models of a variety of compounds with varying selectivity for AMPA over other glutamate receptor subtypes. CP-465,022 is a new, potent, and selective nonc...

AMPA and NMDA receptors mediate most excitatory synaptic transmission in the CNS. We have developed antibodies that recognize all AMPA or all NMDA receptor variants on the surface of living neurons. AMPA receptor variants were identified with a polyclonal antibody recognizing the conserved extracellular loop region of all four AMPA receptor subunits (GluR1-4, both flip and flop), whereas NMDA r...

Recent evidence suggests that Ca(2+)-permeable AMPA receptors display rapid, short-lasting current facilitation. In this study, we investigated the properties of AMPA receptor-mediated synaptic currents in medial septal neurons of the rat in an in vitro slice preparation. Immunocytochemistry with a selective antibody to the GluR2 subunit revealed that both choline acetyltransferase-containing a...

Both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-D-aspartate (NMDA) glutamatergic receptor subtypes in hippocampus have been shown to express long-term potentiation (LTP), a form of synaptic modification believed to be involved in memory formation. Because of their postsynaptic localization, any differential expression of LTP by the two receptor subtypes would stro...

Removal of synaptic AMPA receptors is important for synaptic depression. Here, we characterize the roles of individual subunits in the inducible redistribution of AMPA receptors from the cell surface to intracellular compartments in cultured hippocampal neurons. The intracellular accumulation of GluR2 and GluR3 but not GluR1 is enhanced by AMPA, NMDA, or synaptic activity. After AMPA-induced in...

AMPA receptor-mediated excitotoxicity has been implicated in the pathogenesis of stroke, neurotrauma, epilepsy, and many neurodegenerative diseases such as motoneuron disease. We studied the role of Cl- in AMPA receptor-mediated Ca2+-dependent excitotoxicity in cultured rat spinal motoneurons. Using the gramicidin perforated patch-clamp technique, the intracellular Cl- concentration could be ca...

Endocytosis of postsynaptic AMPA receptors is a mechanism through which efficiency of neurotransmission is regulated. We have genetically tested the hypothesis that synaptojanin 1, a phosphoinositide phosphatase implicated in the endocytosis of synaptic vesicles presynaptically, may also function in the endocytosis of AMPA receptors postsynaptically. Electrophysiological recordings of cultured ...

Maturation of the glutamatergic synapse is thought to require the incorporation of AMPA receptors at pure NMDA synapses, also called "silent" synapses. However, the relative number of silent synapses at different developmental stages, and even the concept that silent synapses lack AMPA receptors, is actively debated. In the present work, spontaneous synaptic events were used to investigate the ...

Whole-cell or outside-out patch recordings were used to investigate the effects of protons and positive modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on the desensitization of glutamate-evoked AMPA receptor currents in isolated hippocampal CA1 neurons. Protons inhibited glutamate-evoked currents (IC(50) of 6.2 pH units) but also enhanced the apparent ra...

A variety of evidence suggests that the effects of light on the mammalian circadian system are mediated by direct retinal ganglion cell projection to the suprachiasmatic nucleus (SCN). This synaptic connection is glutamatergic and the release of glutamate is detected by both N-methyl-D-asparate (NMDA) and amino-methyl proprionic acid/kainate (AMPA/KA) iontotropic glutamate receptors (GluRs). It...