mTOR signaling in the hippocampus is necessary for memory formation

PEDRO BEKINSCHTEIN; CYNTHIA KATCHE; LEANDRO N. SLIPCZUK; LIONEL MÜLLER IGAZ; MARTÍN CAMMAROTA; IVAN IZQUIERDO; JORGE H. MEDINA

NEUROBIOLOGY OF LEARNING AND MEMORY

Elsevier Inc.

Lugar: Orlando, FLorida; Año: 2007 vol. 87 p. 303 - 307

1074-7427

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.