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1. Intracellular recording techniques were used to characterize monosynaptic inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in rat hippocampal slices and to study the mechanism of paired-pulse depression of these synaptic responses. This was achieved by stimulation in stratum radiatum close (less than 0.5 mm) to an intracellularly recorded(More)
The N-methyl-D-aspartate (NMDA)-subtype of glutamate receptors has been well described as a result of the early appearance of NMDA antagonists, but no potent antagonist for the "non-NMDA" glutamate receptors has been available. Quinoxalinediones have now been found to be potent and competitive antagonists at non-NMDA glutamate receptors. These compounds(More)
The vanilloid receptor VR1 is a nonselective cation channel that is most abundant in peripheral sensory fibers but also is found in several brain nuclei. VR1 is gated by protons, heat, and the pungent ingredient of "hot" chili peppers, capsaicin. To date, no endogenous compound with potency at this receptor comparable to that of capsaicin has been(More)
Axonal injury is considered the major cause of disability in patients with multiple sclerosis (MS), but the underlying effector mechanisms are poorly understood. Starting with a proteomics-based approach, we identified neurofascin-specific autoantibodies in patients with MS. These autoantibodies recognize the native form of the extracellular domains of both(More)
We have examined the effects of ketamine and kynurenate on the initial response and frequency dependent potentiation of response (wind-up) of class 2 neurones of the rat dorsal horn induced by repeated electrical stimulation of their receptive fields. Iontophoretic kynurenate reduced both the initial response and the wind-up. Iontophoretic or intravenous(More)
Neurotransmission at most excitatory synapses in the brain operates through two types of glutamate receptor termed alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors; these mediate the fast and slow components of excitatory postsynaptic potentials respectively. Activation of NMDA receptors can also lead to(More)
Long-term potentiation (LTP) in the hippocampus is widely studied as the mechanisms involved in its induction and maintenance are believed to underlie fundamental properties of learning and memory in vertebrates. Most synapses that exhibit LTP use an excitatory amino-acid neurotransmitter that acts on two types of receptor, the N-methyl-D-aspartate (NMDA)(More)
The new antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which blocks responses to kainate and quisqualate, has been used in conjunction with D-2-amino-5-phosphonovalerate (APV), which blocks selectively responses to N-methyl-D-aspartate (NMDA), to determine the role of excitatory amino acid receptors in synaptic transmission. An excitatory(More)
Incubation of rat hippocampal slices in the presence of the synthetic cannabinoid (-)-11-OH-delta 8-dimethylheptyl tetrahydrocannabinol (HU-210) (100 nM) prevented the induction of long-term potentiation (LTP). Slices co-incubated with both HU-210 (100 nM) and the cannabinoid antagonist, SR141716A (100 nM), exhibited tetanically induced LTP, comparable to(More)
Cannabinoids cause an increase in synaptic transmission via gamma-aminobutyric acid (GABA) receptors and this may be the mechanism by which activation of CB1 receptors blocks the induction of long-term potentiation (LTP). To test this hypothesis, we used paired pulse depression (PPD) of CA1 population spike responses recorded in the rat hippocampal slice as(More)