In addition to its effects on neuronal survival and differentiation, brain-derived neurotrophic factor (BDNF) plays an important role in modulating synaptic transmission and plasticity in many brain areas, most notably the neocortex and hippocampus. These effects may underlie a role for BDNF in learning and memory as well as developmental plasticity. Consistent with localization of the trkB rec...

Background : New antidepressant strategies are needed, due to unsatisfactory clinical efficacy and many side effects of commonly used drugs. Recent studies linking the pathophysiology depression with glutamatergic imbalance. There is hyperactivity main excitatory system (glutamatergic) its inhibition (GABAergic). N-methyl D-aspartate (NMDA) receptors as a part synapses potential targets for int...

Chronic ethanol abuse causes up-regulation of NMDA receptors, which underlies seizures and brain damage upon ethanol withdrawal (EW). Here we show that tissue-plasminogen activator (tPA), a protease implicated in neuronal plasticity and seizures, is induced in the limbic system by chronic ethanol consumption, temporally coinciding with up-regulation of NMDA receptors. tPA interacts with NR2B-co...

Optimal function of neuronal networks requires interplay between rapid forms of Hebbian plasticity and homeostatic mechanisms that adjust the threshold for plasticity, termed metaplasticity. Numerous forms of rapid synapse plasticity have been examined in detail. However, the rules that govern synaptic metaplasticity are much less clear. Here, we demonstrate a local subunit-specific switch in N...

Activation and Thr286 autophosphorylation of calcium/calmodulindependent kinase II (CaMKII) following Ca2+ influx via N-methyl-D-aspartate (NMDA)-type glutamate receptors is essential for hippocampal long term potentiation (LTP), a widely investigated cellular model of learning and memory. Here, we show that NR2B, but not NR2A or NR1, subunits of NMDA receptors are responsible for autophosphory...

The midbrain periaqueductal grey (PAG) is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to invest...

The potency of Pb2+ inhibition of glutamate-activated currents mediated by N-methyl-D-aspartate (NMDA) receptors was dependent on the subunits composing the receptors when functionally expressed in Xenopus laevis oocytes. Pb2+ reduced the amplitudes of glutamate-activated currents and shifted the agonist EC50 values of NMDA receptors consisting of different subunit compositions. The IC50 values...

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...

The N-methyl-D-aspartate (NMDA) receptor has long been implicated in the pathophysiology of schizophrenia. NMDA receptor antagonists induce psychotic states in humans and when administered to rodents promote lasting behavioural phenotypes relevant to schizophrenia (Javitt and Zukin, 1991; Abi-Saab et al., 1998; Javitt, 2007). Further, schizophrenia brain tissue contains reduced expression and f...

Evidence is accumulating for a role for amyloid peptides in impaired synaptic plasticity and cognition, while the underlying mechanisms remain unclear. We here analyzed the effects of amyloid peptides on NMDA-receptor function in vitro and in vivo. A synthetic amyloid peptide preparation containing monomeric and oligomeric A beta (1-42) peptides was used and demonstrated to bind to synapses exp...