A direct relationship has been established between synaptic activity and amyloid-β secretion. Dysregulation of neuronal calcium homeostasis was shown to increase production of amyloid-β, contributing to the initiation of Alzheimer's disease. Among the different routes of Ca(2+) entry, N-methyl-d-aspartate (NMDA) receptors, a subtype of ionotropic glutamate receptors, are especially involved in ...

The perforant path constitutes the primary projection system relaying information from the neocortex to the hippocampal formation. Long-term synaptic potentiation (LTP) in the perforant path projections to the dentate gyrus is well characterized. However, surprisingly few studies have addressed the mechanisms underlying LTP induction in the direct perforant path projections to the hippocampus. ...

NMDA receptor (NMDAR) antagonists are dissociative anesthetics, drugs of abuse, and are of therapeutic interest in neurodegeneration and neuropsychiatric disease. Many well-known NMDAR antagonists are positively charged, voltage-dependent channel blockers. We recently showed that the hydrophobic anion dipicrylamine (DPA) negatively regulates GABA(A) receptor function by a mechanism indistinguis...

The main objective of this study was to establish the contribution of NMDA receptors to natural processing of somatosensory information within rat SI barrel cortex. Responses of 52 cells in layers I-IV of the rat barrel cortex were analyzed by PSTH (peristimulus histogram) analysis of evoked spikes in reply to brief deflections of the principal whisker in animals anesthetized with urethane. Sho...

introduction: n-methyl-d-aspartate (nmda) receptors play a pivotal role in the development of tolerance and physical dependence to opiates. activation of nmda receptors involves the induction of long term potentiation (ltp) in hippocampus. our previous study suggested that chronic oral administration of morphine enhanced nmda dependent ltp in the ca1 area of hippocampal slices of rats. the pres...

background and objective: regarding the prevalence of epilepsy in human society and with respect to insufficiency of usual treatments, new strategies and methods for medical treatment of epileptic patients are necessary. as nmda receptor antagonists are the most prominent anti-epileptic drugs, in the present study, we synthesized and investigated anti-epileptic effect of a new piperidine deriva...

We previously reported that the histamine H1 receptor antagonist terfenadine enhances the excitotoxic response to N-methyl-D-aspartate (NMDA) receptor agonists in cerebellar neurons. Here we investigated whether this unexpected action of terfenadine relates to its antihistamine activity, and which specific events in the signal cascade coupled to NMDA receptors are affected by terfenadine. Low c...

In the mammalian brain, new neurons are continuously generated throughout life in the dentate gyrus (DG) of the hippocampus. Previous studies have established that newborn neurons migrate a short distance to be integrated into a preexisting neuronal circuit in the hippocampus. How the migration of newborn neurons is governed by extracellular signals, however, has not been fully understood. Here...

Impairment of insulin-like growth factor I (IGF-I) signaling plays an important role in the development of neurodegeneration. In the present study, we investigated the effect of H2O2 on the survival signaling of IGF-1 and its underlying mechanisms in human neuronal cells SH-SY5Y. Our results showed that IGF-1 promoted cell survival and stimulated phosphorylation of IGF-1R as well as its downstr...

We have used confocal microscopy to monitor synaptically evoked Ca2+ transients in the dendritic spines of hippocampal pyramidal cells. Individual spines respond to single afferent stimuli (<0.1 Hz) with Ca2+ transients or failures, reflecting the probability of transmitter release at the activated synapse. Both AMPA and NMDA glutamate receptor antagonists block the synaptically evoked Ca2+ tra...