The activity of the NMDA receptor (NMDAR), which is a glutamate-gated ion channel, is a key factor influencing the neuronal damage following cerebral ischemia. NMDAR is composed of two essential GluN1 subunits and two regionally localized GluN2 or GluN3 subunits. GluN1, GluN2A, and GluN2B are the primary NMDAR subunits in the adult forebrain. Thus, the three major NMDAR subtypes in the adult fo...

BACKGROUND N-methyl-D-aspartate (NMDA) receptors play a central role in glutamatergic synaptic transmission in the mammalian brain and are linked to the pathophysiology and symptomatology of Parkinson's disease (PD). However, changes in NMDA receptor expression in distinct subcellular compartments in PD have not been elucidated. In this study, we investigated changes in subcellular expression o...

NMDA receptors (NMDARs) form glutamate-gated ion channels that have central roles in neuronal communication and plasticity throughout the brain. Dysfunctions of NMDARs are involved in several central nervous system disorders, including stroke, chronic pain and schizophrenia. One hallmark of NMDARs is that their activity can be allosterically regulated by a variety of extracellular small ligands...

The reduced expression of the Sp4 gene in Sp4 hypomorphic mice resulted in subtle vacuolization in the hippocampus as well as deficits in sensorimotor gating and contextual memory, putative endophenotypes for schizophrenia and other psychiatric disorders. In this study, we examined both spatial learning/memory and hippocampal long-term potentiation (LTP) of Sp4 hypomorphic mice. Impaired spatia...

BACKGROUND The role of N-Methyl-D-aspartate (NMDA) receptors is critical to the development of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in Parkinson's disease (PD). Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is thought to regulate the expression and activation of NMDA receptors in LID, but the interaction between LID and CaMKII-modulated NMDA receptor activity ...

During development there is an activity-dependent switch in synaptic N-Methyl-D-aspartate (NMDA) receptor subunit composition from predominantly GluN2B to GluN2A, though the precise role of this switch remains unknown. By deleting GluN2 subunits in single neurons during synaptogenesis, we find that both GluN2B and GluN2A suppress AMPA receptor expression, albeit by distinct means. Similar to Gl...

The defining functional feature of N-methyl-d-aspartate (NMDA) receptors is activation gating, the energetic coupling of ligand binding into opening of the associated ion channel pore. NMDA receptors are obligate heterotetramers typically composed of glycine-binding GluN1 and glutamate-binding GluN2 subunits that gate in a concerted fashion, requiring all four ligands to bind for subsequent ope...

ICAM-5 is a negative regulator of dendritic spine maturation and facilitates the formation of filopodia. Its absence results in improved memory functions, but the mechanisms have remained poorly understood. Activation of NMDA receptors induces ICAM-5 ectodomain cleavage through a matrix metalloproteinase (MMP)dependent pathway, which promotes spine maturation and synapse formation. Here, we rep...

N-methyl-d-aspartate receptors (NMDARs) are ion channels whose synaptic versus extrasynaptic localization critically influences their functions. This distribution of NMDARs is highly dependent on their lateral diffusion at the cell membrane. Each obligatory subunit of NMDARs (GluN1 and GluN2) contains two extracellular clamshell-like domains with an agonist-binding domain and a distal N-termina...

N-methyl-D-aspartate (NMDA) receptor activation involves a dynamic series of structural rearrangements initiated by glutamate binding to glycine-loaded receptors and culminates with the clearing of the permeation pathway, which allows ionic flux. Along this sequence, three rate-limiting transitions can be quantified with kinetic analyses of single-channel currents, even though the structural de...