Long-lasting LTP requires neither repeated trains for its induction nor protein synthesis for its development

PLoS One. 2012;7(7):e40823. doi: 10.1371/journal.pone.0040823. Epub 2012 Jul 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Electric Stimulation
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Long-Term Potentiation / physiology*
  • Memory / physiology*
  • Mice
  • N-Methylaspartate / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology*
  • Protein Synthesis Inhibitors / pharmacology
  • Receptors, AMPA / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Protein Synthesis Inhibitors
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • Phosphatidylinositol 3-Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • glutamate receptor ionotropic, AMPA 1