BDNF regulates translation through mTOR/p70S6K signaling in memory consolidation of a fear-motivated learning task

SLIPCZUK L.; BEKINSCHTEIN P.; KATCHE C.; CAMMAROTA M.; IZQUIERDO I.; MEDINA JH.

Santiago de Chile, Chile.

Workshop; Neuronal signalling and plasticity course; 2008

Universidad de Chile

It is widely accepted that consolidation 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, nevertheless its upstream and downstream signaling in memory formation remains unknown. Here, we show that LTM formation of one-trial inhibitory avoidance (IA) in rats, a hippocampus-dependent fear-motivated learning task, requires mTOR during training and 3hs afterwards.Bilateral intra-CA1 infusion of rapamycin, a selective mTOR inhibitor, 15 min before, or 3 hs after training completely hinders IA LTM without affecting short-term memory (STM) retention. Blocking BDNF activity hinders mTOR activity produced by IA learning, and blocking BDNF or mTOR activity blocks GluR1 expression induced by learning in a synaptic terminals enriched subcellular fraction. Therefore, our findings indicate that the regulation of hippocampal mRNA translation has two windows of activity required for IA consolidation through BDNF/mTOR signaling.