mTOR inhibition impairs extinction memory reconsolidation

Fear-motivated avoidance extinction memory is prone to hippocampal brain-derived neurotrophic factor (BDNF)-dependent reconsolidation upon recall. Here, we show that extinction memory recall activates mammalian target of rapamycin (mTOR) in dorsal CA1, and that post-recall inhibition of this kinase hinders avoidance extinction memory persistence and recovers the learned aversive response. Importantly, coadministration of recombinant BDNF impedes the behavioral effect of hippocampal mTOR inhibition. Our results demonstrate that mTOR signaling is necessary for fear-motivated avoidance extinction memory reconsolidation and suggests that BDNF acts downstream mTOR in a protein synthesis-independent manner to maintain the reactivated extinction memory trace.

Automated summary

Fear-motivated avoidance extinction memory is reconsolidated upon recall through hippocampal BDNF-dependent pathway, which involves activation of mTOR in dorsal CA1. Inhibition of mTOR post-recall hinders memory persistence, while coadministration of recombinant BDNF impedes mTOR inhibition from affecting the memory trace. This suggests that mTOR signaling is essential for fear-motivated avoidance extinction memory reconsolidation and BDNF may act downstream mTOR in a protein synthesis-independent manner.