Home About us Contact
|
Home About us Contact | ||
|
|
||
Hippocampal Long-term Potentiation (hippocampal + long-term_potentiation)
Selected AbstractsCD4+CD25, effector T-cells inhibit hippocampal long-term potentiation in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Gil M. Lewitus Abstract During neuroinflammation T-cells invade the CNS, and may lead to the development and progression of several pathologies, of which multiple sclerosis is the most common. In these pathologies neuroinflammation is often associated with cognitive dysfunction. Using mouse hippocampal slices, we show here that CD4+CD25, T-cells inhibit long-term potentiation (LTP) induced by high-frequency stimulation. The T-cell-mediated inhibition of LTP can be prevented by blockade of ,-aminobutyric acid (GABA)A receptors. These findings provide additional insight into the multiple functions of T-cells in CNS pathologies. [source] Repeated withdrawal from ethanol spares contextual fear conditioning and spatial learning but impairs negative patterning and induces over-responding: evidence for effect on frontal cortical but not hippocampal function?EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2006Gilyana G. Borlikova Abstract Repeated exposure of rats to withdrawal from chronic ethanol reduces hippocampal long-term potentiation and gives rise to epileptiform-like activity in hippocampus. We investigated whether such withdrawal experience also affects learning in tasks thought to be sensitive to hippocampal damage. Rats fed an ethanol-containing diet for 24 days with two intermediate 3-day withdrawal episodes, resulting in intakes of 13,14 g/kg ethanol per day, showed impaired negative patterning discrimination compared with controls and animals that had continuous 24-day ethanol treatment, but did not differ from these animals in the degree of contextual freezing 24 h after training or in spatial learning in the Barnes maze. Repeatedly withdrawn animals also showed increased numbers of responses in the period immediately before reinforcement became available in an operant task employing a fixed-interval schedule although overall temporal organization of responding was unimpaired. Thus, in our model of repeated withdrawal from ethanol, previously observed changes in hippocampal function did not manifest at the behavioural level in the tests employed. The deficit seen after repeated withdrawal in the negative patterning discrimination and over-responding in the fixed-interval paradigm might be related to the changes in the functioning of the cortex after withdrawal. [source] Melatonin inhibits hippocampal long-term potentiationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2005Louisa M. Wang Abstract The goal of this study is to investigate the effect of the hormone melatonin on long-term potentiation and excitability measured by stimulating the Schaffer collaterals and recording the field excitatory postsynaptic potential from the CA1 dendritic layer in hippocampal brain slices from mice. Application of melatonin produced a concentration-dependent inhibition of the induction of long-term potentiation, with a concentration of 100 nm producing an ,,50% inhibition of long-term potentiation magnitude. Long-duration melatonin treatments of 6 h were also effective at reducing the magnitude of long-term potentiation. Melatonin (100 nm) did not alter baseline evoked responses or paired-pulse facilitation recorded at this synapse. The inhibitory actions of melatonin were prevented by application of the melatonin (MT) receptor antagonist luzindole as well as the MT2 receptor subtype antagonist 4-phenyl-2-propionamidotetraline. These inhibitory actions of melatonin were lost in mice deficient in MT2 receptors but not those deficient in MT1 receptors. In addition, application of the protein kinase A inhibitor H-89 both mimicked the effects of melatonin and precluded further inhibition by melatonin. Finally, the application an activator of adenylyl cyclase, forskolin, overcame the inhibitory effects of melatonin on LTP without affecting the induction of long-term potentiation on its own. These results suggest that hippocampal synaptic plasticity may be constrained by melatonin through a mechanism involving MT2-receptor-mediated regulation of the adenylyl cyclase,protein kinase A pathway. [source] A single application of MK801 causes symptoms of acute psychosis, deficits in spatial memory, and impairment of synaptic plasticity in ratsHIPPOCAMPUS, Issue 2 2008Denise Manahan-Vaughan Abstract Schizophrenia is mostly a progressive psychiatric illness. Although cognitive changes in chronic schizophrenia have been investigated, little is known about the consequences of a single psychotic episode on memory mechanisms and formation. We investigated changes in hippocampal long-term potentiation (LTP) and spatial memory in a rat model of an acute psychotic episode. Application of NMDA receptor antagonists, such as MK801 (dizolcilpine) in rats, have been shown to give rise to an acute and short-lasting behavioral state, which mirrors many symptoms of schizophrenia. Furthermore, NMDA antagonist-intake in humans elicits symptoms of schizophrenia such as hallucinations, delusions, and affective blunting. We therefore treated animals with a single systemic injection of MK801 (5 mg/kg). Increased stereotypy, locomotion, and ataxia were evident immediately after MK801-treatment, with effects disappearing within 24 h. MK801-treatment caused a disruption of prepulse inhibition of the acoustic startle reflex, 1 day but not 7 or 28 days after treatment. These effects were consistent with the occurrence of an acute psychotic episode. LTP was profoundly impaired in freely moving rats 7 days after MK801 application. Four weeks after treatment, a slight recovery of LTP was seen, however marked deficits in long-term spatial memory were evident. These data suggest that treatment with MK801 to generate an acute psychotic episode in rats, gives rise to grave disturbances in synaptic plasticity and is associated with lasting impairments with the ability to form spatial memory. © 2007 Wiley-Liss, Inc. [source] Transcription factor NF-,B activation after in vivo perforant path LTP in mouse hippocampusHIPPOCAMPUS, Issue 6 2004Ramiro Freudenthal Abstract There is increasing evidence that transcription factors (TFs) play a critical role in maintaining later phases of hippocampal long-term potentiation (LTP). We have been led to study the role in synaptic plasticity of the powerful, yet generally unheralded, NF-,B TF because it may serve as both a signaling molecule after its activation at the synapse and then a transcription initiator upon reaching the nucleus. In the present study, we show that LTP activates NF-,B in the intact mouse hippocampus. Mice were sacrificed 15 min after one of three treatments: tetanization (high-frequency stimulation [HFS]), low-frequency stimulation (LFS), or no stimulated control animals (CT). In a first study, nuclear NF-,B activity from hippocampus was estimated by electrophoretic mobility shift assays (EMSAs). A higher level of hippocampal TF binding to the NF-,B recognition element was found in the HFS group compared with LFS or CT. In a second study, NF-,B activity was evaluated by immunohistochemistry with a specific antibody that recognizes the activated form of NF-,B. This antibody binds to the exposed nuclear location sequence on the p65 subunit of NF-,B consequent to its dissociation from the inhibitory I,B molecule. In the four subfields of hippocampus examined,granule cell layer, hilus of the dentate gyrus, CA3 and CA1 pyramidal fields of the hippocampal gyrus,the highest levels of activated NF-,B, statistically significant in all cases were found after HFS. In certain comparisons, LFS animals also showed significant elevation with respect to CT. These results support the role of NF-,B as part of the synaptic signaling and transcriptional regulation mechanism required in long-term plasticity, emphasizing the combinatorial nature of TF function. © 2004 Wiley-Liss, Inc. [source] ,-Tocopheryl phosphate , An active lipid mediator?MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2010Jean-Marc Zingg Abstract The vitamin E (,-tocopherol, ,T) derivative, ,-tocopheryl phosphate (,TP), is detectable in small amounts in plasma, tissues, and cultured cells. Studies done in vitro and in vivo suggest that ,T can become phosphorylated and ,TP dephosphorylated, suggesting the existence of enzyme(s) with ,T kinase or ,TP phosphatase activity, respectively. As a supplement in animal studies, ,TP can reach plasma concentrations similar to ,T and only a part is dephosphorylated; thus, ,TP may act both as pro-vitamin E, but also as phosphorylated form of vitamin E with possibly novel regulatory activities. Many effects of ,TP have been described: in the test tube ,TP modulates the activity of several enzymes; in cell culture ,TP affects proliferation, apoptosis, signal transduction, and gene expression; in animal studies ,TP prevents atherosclerosis, ischemia/reperfusion injury, and induces hippocampal long-term potentiation. At the molecular level, ,TP may act as a cofactor for enzymes, as an active lipid mediator similar to other phosphorylated lipids, or indirectly by altering membrane characteristics such as lipid rafts, fluidity, and curvature. In this review, the molecular and cellular activities of ,TP are examined and the possible functions of ,TP as a natural compound, cofactor and active lipid mediator involved in signal transduction and gene expression discussed. [source] A new amyloid , variant favoring oligomerization in Alzheimer's-type dementiaANNALS OF NEUROLOGY, Issue 3 2008Takami Tomiyama PhD Objective Soluble oligomers of amyloid , (A,), rather than amyloid fibrils, have been proposed to initiate synaptic and cognitive dysfunction in Alzheimer's disease (AD). However, there is no direct evidence in humans that this mechanism can cause AD. Here, we report a novel amyloid precursor protein (APP) mutation that may provide evidence to address this question. Methods A Japanese pedigree showing Alzheimer's-type dementia was examined for mutations in APP, PSEN1, and PSEN2. In addition, 5,310 Japanese people, including 2,121 patients with AD, were screened for the novel APP mutation. The pathogenic effects of this mutation on A, production, degradation, aggregation, and synaptotoxicity were also investigated. Results We identified a novel APP mutation (E693,) producing variant A, lacking gulutamate-22 (E22,) in Japanese pedigrees showing Alzheimer's-type dementia and AD. Although the secretion of total A, was markedly reduced by this mutation, the variant A, was more resistant to proteolytic degradation. The mutant peptides showed the unique aggregation property of enhanced oligomerization but no fibrillization, and inhibited hippocampal long-term potentiation more potently than wild-type peptide in rats in vivo. Consistent with the nonfibrillogenic property of the variant A,, a very low amyloid signal was observed in the patient's brain on positron emission tomography using Pittsburgh compound-B. Interpretation The E693, mutation has been suggested as a cause of dementia because of enhanced formation of synaptotoxic A, oligomers. Our findings may provide genetic validation in humans for the emerging hypothesis that the synaptic and cognitive impairment in AD is primarily caused by soluble A, oligomers. Ann Neurol 2008 [source] | ||||||||||