Recent evidence has linked striatal N-methyl-D-aspartate (NMDA) receptor function to the adverse effects of long-term dopaminergic treatment in Parkinson's disease. We have studied the abundance, composition, and phosphorylation of NMDA receptor subunits (NRs) in the rat 6-hydroxydopamine lesion model of parkinsonism. In lesioned striatum, the abundance of NR1 and NR2B in striatal membranes was...

Spinal NMDA receptor (NMDAR), protein kinase C (PKC), and glucocorticoid receptor (GR) have all been implicated in the mechanisms of morphine tolerance; however, how these cellular elements interact after chronic morphine exposure remains unclear. Here we show that the expression of spinal NMDAR and PKCgamma after chronic morphine is regulated by spinal GR through a cAMP response element-bindin...

Epidemiological studies have suggested a negative correlation between alcohol intake and Alzheimer's disease. In vitro, ethanol negatively modulates NMDA receptor function. We hypothesized that chronic moderate alcohol intake leads to improved memory via adaptive responses in the expression of NMDA receptors and downstream signaling. We fed liquid diets containing no, moderate, or high amounts ...

Classical conditioning of the eyeblink reflex is a simple form of associative learning for motor responses. To examine the involvement of hippocampal CA3 NMDA receptors (NRs) in nonspatial associative memory, mice lacking an NR1 subunit selectively in adult CA3 pyramidal cells [CA3-NR1 knock-out (KO) mice] were subjected to eyeblink conditioning paradigms. Mice received paired presentations of ...

To study potential molecular mechanisms of epileptogenesis in the neocortex, the motor cortex of rats was injected with tetanus toxin (TT), and gene expression for 67 kDa glutamic acid decarboxylase (GAD-67), type II calcium/calmodulin-dependent protein kinase (CaMKII), NMDA receptor subunit 1 (NR1), and AMPA receptor subunit 2 (GluR2) was investigated by in situ hybridization histochemistry. I...

OF THESIS TIME-DEPENDENCE OF DISTAL-TO-PROXIMAL HIPPOCAMPAL NEURODEGENERATION PRODUCED BY N-METHYL-D-ASPARTATE RECEPTOR ACTIVATION Excitotoxicity is the overexcitation of neurons due to the excessive activation of excitatory amino acid receptors and is thought to be involved in many neurodegenerative states. The manner in which the neuron breaks down during excitotoxicity is still unclear. The ...

Retinal ganglion cells (RGCs) receive excitatory glutamatergic input from ON and OFF bipolar cells in distinct sublaminae of the inner plexiform layer (IPL). AMPA and NMDA receptors (AMPARs and NMDARs) mediate excitatory inputs in both synaptic layers, but specific roles for NMDARs at RGC synapses remain unclear. NMDARs comprise NR1 and NR2 subunits and are anchored by membrane-associated guany...

During postnatal development, changes in the subunit composition of glutamate receptors of the NMDA subtype (NMDARs) are key to the refinement of excitatory synapses. Hypotheses for maturation of synaptic NMDARs include regulation of their expression levels, membrane targeting, and surface movements. In addition, several members of extracellular matrix (ECM) proteins such as Reelin are involved...

Extracellular protons inhibit N-methyl-D-aspartate (NMDA) receptors with an IC50 value in the physiological pH range. To identify the molecular determinants of proton sensitivity, we used scanning mutagenesis of the NR1 subunit to search for residues that control proton inhibition of NMDA receptors. Homology modeling of the extracellular domains suggested that residues at which mutations pertur...

Glutaminase-deficient mice (GLS1 hets), with reduced glutamate recycling, have a focal reduction in hippocampal activity, mainly in CA1, and manifest behavioral and neurochemical phenotypes suggestive of schizophrenia resilience. To address the basis for the hippocampal hypoactivity, we examined synaptic plastic mechanisms and glutamate receptor expression. Although baseline synaptic strength w...