Phosphatidylinositol 3-kinase is required for the expression but not for the induction or the maintenance of long-term potentiation in the hippocampal CA1 region
| Autor: | Sanna, Pp, Cammalleri, Maurizio, Berton, Fulvia, Simpson, C, Lutjens, R, Bloom, Fe, Francesconi, W., Neurosci, J. |
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| Rok vydání: | 2002 |
| Předmět: |
Morpholines
Long-Term Potentiation Stimulation In Vitro Techniques Protein Serine-Threonine Kinases Biology Hippocampal formation Hippocampus GABA Antagonists Wortmannin Phosphatidylinositol 3-Kinases chemistry.chemical_compound Proto-Oncogene Proteins LTP induction medicine Animals Phosphatidylinositol Enzyme Inhibitors Rats Wistar ARTICLE Phosphoinositide-3 Kinase Inhibitors Ribosomal Protein S6 Kinases musculoskeletal neural and ocular physiology General Neuroscience Excitatory Postsynaptic Potentials Long-term potentiation Calcium Channel Blockers Electric Stimulation Rats Androstadienes Enzyme Activation medicine.anatomical_structure nervous system chemistry Chromones Schaffer collateral Synapses Calcium Channels Signal transduction Excitatory Amino Acid Antagonists Proto-Oncogene Proteins c-akt Neuroscience Signal Transduction |
| Popis: | Several signal transduction pathways have been implicated in the induction of long-term potentiation (LTP), yet the signal transduction mechanisms behind the maintenance–expression phase of LTP are still poorly understood. We investigated the role of phosphatidylinositol 3-kinase (PI3-kinase) in LTP at Schaffer collateral/commissural fiber–CA1 synapses in rat hippocampal slices using biochemical approaches and extracellular electrophysiological recordings. We observed that PI3-kinase activity was induced in the CA1 region during LTP of field EPSPs (fEPSPs) and that two structurally unrelated PI3-kinase inhibitors, LY294002 and wortmannin, abated established LTP, suggesting that PI3-kinase is involved in the maintenance–expression phase of LTP. However, LTP recovered after washout of the reversible PI3-kinase inhibitor LY294002, confirming that LTP maintenance and expression are distinct events and indicating that PI3-kinase activity is required for LTP expression rather than for its maintenance. Interestingly, preincubation with LY294002 did not prevent LTP induction. In fact, if LY294002 was withdrawn 5 min after high-frequency stimulation, an LTP of fEPSP was seen. Last, a voltage-dependent calcium channel-dependent form of LTP in the CA1 could also be reversibly abated by LY294002, raising the possibility that PI3-kinase could be required for the expression of multiple forms of synaptic potentiation. |
| Databáze: | OpenAIRE |
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