Based on results from the kindling model of epilepsy, we hypothesized that enhanced binding of radioligands to the NMDA receptor and decreased binding to the alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA)-sensitive quisqualate (ASQ) receptor would be found within epileptic hippocampi of humans with complex partial epilepsy (CPE). To test these hypotheses, we used tissue that was s...

Both serotonin and NMDA signaling in prefrontal cortex (PFC) are implicated in mental disorders, including depression and anxiety. To understand their potential contributions to PFC neuronal excitability, we examined the effect of co-activation of 5-HT and NMDA receptors on action potential firing elicited by depolarizing current injection in PFC pyramidal neurons. In the presence of NMDA, a lo...

ATP and glutamate are fast excitatory neurotransmitters in the central nervous system acting primarily on ionotropic P2X and glutamate [N-methyl-D-aspartate (NMDA) and non-NMDA] receptors, respectively. Both neurotransmitters regulate synaptic plasticity and long-term potentiation in hippocampal neurons. NMDA receptors are responsible primarily for the modulatory action of glutamate, but the me...

17-β-estradiol (E2) is a steroid hormone involved in neuroprotection against excitotoxicity and other forms of brain injury. Through genomic and nongenomic mechanisms, E2 modulates neuronal excitability and signal transmission by regulating NMDA and non-NMDA receptors. However, the mechanisms and identity of the receptors involved remain unclear, even though studies have suggested that estrogen...

Prefrontal cortex (PFC) functions, such as working memory, attention selection, and memory retrieval, depend critically on dopamine and NMDA receptor activation by way of an inverted-U-shaped pharmacological profile. Although single neuron responses in the PFC have shown some aspects of this profile, a network dynamic that follows the dopamine-NMDA dependence has not been identified. We studied...

The receptor pharmacology of cholinergic ("starburst") amacrine cells was studied in a newly developed rabbit retinal slice preparation with whole-cell patch clamp. Displaced starburst cells were labeled with the fluorescent dye 4,6-diamidino-2-phenylindole (DAPI), and their dendritic morphology was identified in the slice with Lucifer yellow. Under conditions in which synaptic transmission was...

This study aims to assess whether the antinociceptive actions of methadone are mediated solely through opioid mechanisms, or whether its reported affinity for NMDA receptors has physiological relevance in vivo. Methadone is a mu-opioid receptor agonist reported to relieve pain unresponsive to other opioids. It is a racemic mixture comprising d- and l-optical isomers; the d-isomer has a lower af...

N-methyl-D-aspartate (NMDA) receptors are glutamate-gated ion channels whose function is critical for normal excitatory synaptic transmission in the brain and whose dysfunction has been implicated in several neurologic conditions. NMDA receptor function is subject to extensive allosteric regulation both by endogenous compounds and by exogenous small molecules. Elucidating the structural determi...

Ionotropic glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype are highly expressed in the central nervous system and are involved in excitatory synaptic transmission and synaptic plasticity. Prolonged activation of NMDA receptors can lead to excitotoxicity, which is implicated in the pathogenesis of neurodegeneration occurring in various acute and chronic disorders of the central ne...

The specification and organization of glutamatergic synaptic transmission require the coordinated interaction among glutamate receptors and their synaptic adaptor proteins closely assembled in the postsynaptic density (PSD). Here we investigated the interaction between NMDA receptors and metabotropic glutamate receptor 5 (mGluR5) in the integral regulation of extracellular signal-regulated prot...