mTOR signaling in the hippocampus is necessary for memory formation

Neurobiol Learn Mem. 2007 Feb;87(2):303-7. doi: 10.1016/j.nlm.2006.08.007. Epub 2006 Sep 26.

Abstract

It is widely accepted that the formation of long-term memory (LTM) requires mRNA translation, but little is known about the cellular mechanisms in the brain that regulate this process. Mammalian target of rapamycin (mTOR) is a key regulator of translational efficacy and capacity. Here, we show that LTM formation of one-trial inhibitory avoidance (IA) in rats, a hippocampus-dependent fear-motivated learning task, requires mTOR activation. IA training is specifically associated with a rapid increase in the phosphorylation state of mTOR and its substrate ribosomal S6 kinase (p70S6K). Bilateral intra-CA1 infusion of rapamycin, a selective mTOR inhibitor, 15 min before, but not immediately after training completely hinders IA LTM without affecting short-term memory (STM) retention. Therefore, our findings indicate that the regulation of hippocampal mRNA translation is a major control step in memory consolidation.

MeSH terms

  • Analysis of Variance
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology
  • Behavior, Animal
  • Blotting, Western
  • Hippocampus / physiology*
  • Male
  • Memory / physiology*
  • Phosphorylation / drug effects
  • Protein Kinases / metabolism*
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases

Substances

  • Protein Kinases
  • TOR Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Sirolimus