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

• Published in: The Journal of neuroscience 2002-05, Vol.22 (9), p.3359-3365
• Main Authors: Sanna, Pietro Paolo, Cammalleri, Maurizio, Berton, Fulvia, Simpson, Cindy, Lutjens, Robert, Bloom, Floyd E, Francesconi, Walter
• Format: Article
• Language: English
• Subjects: Androstadienes - pharmacology; Animals; Calcium Channel Blockers - pharmacology; Calcium Channels - drug effects; Calcium Channels - metabolism; Chromones - pharmacology; Electric Stimulation; Enzyme Activation - drug effects; Enzyme Activation - physiology; Enzyme Inhibitors - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; GABA Antagonists - pharmacology; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - physiology; In Vitro Techniques; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Morpholines - pharmacology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Ribosomal Protein S6 Kinases - metabolism; Signal Transduction - physiology; Synapses - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.22-09-03359.2002

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.