A recently described form of synaptic plasticity results in dynamic changes in the calcium permeability of synaptic AMPA receptors. Since the AMPA receptor GluR2 subunit confers calcium permeability, this plasticity is thought to occur through the dynamic exchange of synaptic GluR2-lacking and GluR2-containing receptors. To investigate the molecular mechanisms underlying this calcium-permeable ...

Transmembrane AMPA receptor regulatory proteins (TARPs) are auxiliary AMPA receptor subunits that regulate both the trafficking and gating properties of AMPA receptors, and different TARP isoforms display distinct expression patterns in brain. Here, we compared the effects of four TARP isoforms on the kinetics of AMPA receptor currents. Each isoform slowed the deactivation of GluR1 currents, bu...

Long-term potentiation (LTP) of excitatory transmission in the hippocampus likely contributes to learning and memory. The mechanisms underlying LTP at these synapses are not well understood, although phosphorylation and redistribution of AMPA receptors may be responsible for this form of synaptic plasticity. We show here that miniature excitatory postsynaptic currents (mEPSCs) in cultured hippo...

In mature neurons AMPA receptors cluster at excitatory synapses primarily on dendritic spines, whereas GABAA receptors cluster at inhibitory synapses mainly on the soma and dendritic shafts. The molecular mechanisms underlying the precise sorting of these receptors remain unclear. By directly studying the constitutive exocytic vesicles of AMPA and GABAA receptors in vitro and in vivo, we demons...

We generated a polyclonal antibody, 12P3, specifically recognizing rat AMPA-type glutamate receptor (GluR) subunits phosphorylated at Ser-696 of GluR2 or at the homologous sites in GluR1, GluR3, and GluR4. Using 12P3, we demonstrate that a brief exposure of a rat cerebellar slice to AMPA leads to transient phosphorylation of the GluR subunits in Purkinje cell dendrites. Persistent phosphorylati...

Dynamic regulation of AMPA-type glutamate receptors represents a primary mechanism for controlling synaptic strength, though mechanisms for this process are poorly understood. The palmitoylated postsynaptic density protein, PSD-95, regulates synaptic plasticity and associates with the AMPA receptor trafficking protein, stargazin. Here, we identify palmitate cycling on PSD-95 at the synapse and ...

Glutamate receptors belonging to the subclass specifically activated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) were solubilized from rat forebrain membranes with Triton X-100 and partially purified through a series of three chromatographic steps. Specific [3H]AMPA binding increased 30-60-fold during the isolation procedure. A protein band recognized by antibodies agains...

Glutamate receptors of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type mediate fast excitatory synaptic transmission in the CNS. Synaptic strength is modulated by AMPA receptor binding partners, which regulate receptor synaptic targeting and functional properties. We identify Contactin-associated protein 1 (Caspr1) as an AMPA receptor interactor. Caspr1 is present in synaps...

The nucleus basalis of Meynert (NBM), a heterogeneous area in the basal forebrain involved in the modulation of sleep and wakefulness, is rich in glutamate receptors, and glutamatergic fibers represent an important part of the input to this nucleus. With the use of unilateral infusions in the NBM, the effects of two different glutamatergic subtype agonists, namely N-methyl-d-aspartic acid (NMDA...

Agonist responses and channel kinetics of native α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are modulated by transmembrane accessory proteins. Stargazin, the prototypical accessory protein, decreases desensitization and increases agonist potency at AMPA receptors. Furthermore, in the presence of stargazin, the steady-state responses of AMPA receptors show a gradual d...