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Long-term Synaptic Plasticity (long-term + synaptic_plasticity)
Selected AbstractsInsulin promotes functional induction of silent synapses in differentiating rat neocortical neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2001Daniela Plitzko Abstract Long-term synaptic plasticity is thought to underlie synaptic reorganization phenomena that occur during neocortical development. Recently, it has been proposed, that the functional induction of AMPA receptors at silent glutamatergic synapses is of major importance in activity-dependent, developmental plasticity. To investigate the mechanisms involved in the developmental regulation of silent synapses, we analysed the functional maturation of the thalamocortical projection in culture. A large proportion of the thalamocortical synapses were functionally silent at an early stage in vitro. During further differentiation, the incidence of silent synapses decreased drastically, indicating a conversion of silent into functional synapses. Chronic blockade of spontaneous network activity by addition of tetrodotoxin to the culture medium strongly impaired this developmental maturation. Moreover, the developmental decline in the proportion of silent synapses was dramatically accelerated by chronic addition of the neurotrophic factor, insulin. This effect of insulin was partly dependent on spontaneous activity. Thus, insulin appears to be involved in the modulation of long-term developmental plasticity at immature glutamatergic synapses. [source] Orexins/hypocretins control bistability of hippocampal long-term synaptic plasticity through co-activation of multiple kinasesACTA PHYSIOLOGICA, Issue 3 2010O. Selbach Abstract Aim:, Orexins/hypocretins (OX/Hcrt) are hypothalamic neuropeptides linking sleep,wakefulness, appetite and neuroendocrine control. Their role and mechanisms of action on higher brain functions, such as learning and memory, are not clear. Methods:, We used field recordings of excitatory post-synaptic potentials (fEPSP) in acute mouse brain slice preparations to study the effects of orexins and pharmacological inhibitors of multiple kinases on long-term synaptic plasticity in the hippocampus. Results:, Orexin-A (OX-A) but not orexin-B (OX-B) induces a state-dependent long-term potentiation of synaptic transmission (LTPOX) at Schaffer collateral-CA1 synapses in hippocampal slices from adult (8- to 12-week-old) mice. In contrast, OX-A applied to slices from juvenile (3- to 4-week-old) animals causes a long-term depression (LTDOX) in the same pathway. LTPOX is blocked by pharmacological inhibition of orexin receptor-1 (OX1R) and plasticity-related kinases, including serine/threonine- (CaMKII, PKC, PKA, MAPK), lipid- (PI3K), and receptor tyrosine kinases (Trk). Inhibition of OX1R, CaMKII, PKC, PKA and Trk unmasks LTDOX in adult animals. Conclusion:, Orexins control not only the bistability of arousal states and threshold for appetitive behaviours but, in an age- and kinase-dependent manner, also bidirectional long-term synaptic plasticity in the hippocampus, providing a possible link between behavioural state and memory functions. [source] Localization of the A kinase anchoring protein AKAP79 in the human hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000Attila Sík Abstract The phosphorylation state of the proteins, regulated by phosphatases and kinases, plays an important role in signal transduction and long-term changes in neuronal excitability. In neurons, cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and calcineurin (CN) are attached to a scaffold protein, A kinase anchoring protein (AKAP), thought to anchor these three enzymes to specific sites of action. However, the localization of AKAP, and the predicted sites of linked phosphatase and kinase activities, are still unknown at the fine structural level. In the present study, we investigated the distribution of AKAP79 in the hippocampus from postmortem human brains and lobectomy samples from patients with intractable epilepsy, using preembedding immunoperoxidase and immunogold histochemical methods. AKAP79 was found in the CA1, presubicular and subicular regions, mostly in pyramidal cell dendrites, whereas pyramidal cells in the CA3, CA2 regions and dentate granule cells were negative both in postmortem and in surgical samples. In some epileptic cases, the dentate molecular layer and hilar interneurons also became immunoreactive. At the subcellular level, AKAP79 immunoreactivity was present in postsynaptic profiles near, but not attached to, the postsynaptic density of asymmetrical (presumed excitatory) synapses. We conclude that the spatial selectivity for the action of certain kinases and phosphatases regulating various ligand- and voltage-gated channels may be ensured by the selective presence of their anchoring protein, AKAP79, at the majority of glutamatergic synapses in the CA1, but not in the CA2/CA3 regions, suggesting profound differences in signal transduction and long-term synaptic plasticity between these regions of the human hippocampus. [source] Translation of striatal-enriched protein tyrosine phosphatase (STEP) after ,1-adrenergic receptor stimulationJOURNAL OF NEUROCHEMISTRY, Issue 2 2007Yaer Hu Abstract The ,-adrenergic system is implicated in long-term synaptic plasticity in the CNS, a process that requires protein synthesis. To identify proteins that are translated in response to ,-adrenergic receptor stimulation and the pathways that regulate this process, we investigated the effects of isoproterenol on the translation of striatal-enriched protein tyrosine phosphatase (STEP) in both cortico-striatal slices and primary neuronal cultures. Isoproterenol stimulation induced a rapid dose-dependent increase in STEP expression. Anisomycin blocked the increase in STEP expression while actinomycin D had no effect, suggesting a translation-dependent mechanism. Isoproterenol-induced STEP translation required activation of ,1-receptors. Application of the MAPK/ERK kinase (MEK) inhibitor SL327 blocked both isoproterenol-induced activation of pERK and subsequent STEP translation. Inhibitors of PI3K (LY294002) or mTOR (rapamycin) also completely blocked STEP translation. These results suggest that co-activation of both the ERK and PI3K-Akt-mTOR pathways are required for STEP translation. As one of the substrates of STEP includes ERK itself, these results suggest that STEP is translated upon ,-adrenergic activation as part of a negative feedback mechanism. [source] Emerging roles for endocannabinoids in long-term synaptic plasticityBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2003Gregory L Gerdeman British Journal of Pharmacology (2003) 140, 781,789. doi:10.1038/sj.bjp.0705466 [source] | ||||||||||