Abstract
Current thinking about LTP triggered in the area CA1 of hippocampal slices is ruled by two “dogmas”: (1) A single train of high-frequency stimulation is sufficient to trigger short-lasting LTP (1 – 3 h), whereas multiple trains are required to induce long-lasting LTP (L-LTP, more than 4 h). (2) The development of the late phase of L-LTP requires the synthesis of new proteins. In this study, we found that a single high-frequency train could trigger an LTP lasting more than 8 h that was not affected by either anisomycin or cycloheximide (two inhibitors of protein synthesis). We ascertained that the induction of this L-LTP made use of the same mechanisms as those usually reported to be involved in LTP induction: it was dependent on NMDA receptors and on the activation of two “core” kinases, CaMKII and PI3K. These findings call into question the two “dogmas” about LTP.
Highlights
Observations on patient H.M. have led to the undisputed idea that two different types of memory exist: short-term memory and long-term memory [1]
A relatively short-lasting long-term potentiation (LTP) (1–3 h) (SLTP) is induced with a single train of high-frequency stimulation (100 Hz, 1 s), whereas triggering a long-lasting LTP (L-LTP) requires repeated trains of stimulation (3 or 4, 5 or 10 min apart) [7]. (2) in analogy with memory, the late phase of L-LTP is believed to depend on a protein synthesis process triggered by the LTP-inducing stimulus whereas the early phase of L-LTP and the S-LTP induced by a single train would rely on post-translational modifications of pre-existing proteins and on incorporation of spare AMPA receptors into the postsynaptic density of the dendritic spines [8]
Studies carried out in rat hippocampal slices have revealed that a single tetanus could trigger a long-lasting LTP [9,10,11,12]
Summary
Observations on patient H.M. have led to the undisputed idea that two different types of memory exist: short-term memory (minutes to a few hours) and long-term memory (days, weeks, years) [1]. From a comprehensive review of experiments carried out on animals, Davis and Squire [2] concluded that short-term memory was independent of protein synthesis whereas long-term memory was prevented by protein-synthesis inhibitors (such as anisomycin) when administered before or just after training. Very popular, this conclusion has recently been questioned [3,4,5,6]. (1) In analogy with memory, LTP is believed to consist of two different temporal phases, each requiring a different type of triggering stimulation. A relatively short-lasting LTP (1–3 h) (SLTP) is induced with a single train of high-frequency stimulation (100 Hz, 1 s), whereas triggering a long-lasting LTP (L-LTP) (more than 4 h) requires repeated trains of stimulation (3 or 4, 5 or 10 min apart) [7]. (2) in analogy with memory, the late phase of L-LTP is believed to depend on a protein synthesis process triggered by the LTP-inducing stimulus whereas the early phase of L-LTP and the S-LTP induced by a single train would rely on post-translational modifications of pre-existing proteins and on incorporation of spare AMPA receptors into the postsynaptic density of the dendritic spines [8]
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