mTOR Inhibition Impairs Extinction Memory Reconsolidation

• Published in: Learning & memory (Cold Spring Harbor, N.Y.) Vol. 28; no. 1; pp. 1 - 6
• Main Authors: Radiske, Andressa, Gonzalez, Maria Carolina, Nôga, Diana A, Rossato, Janine I, Bevilaqua, Lia R. M, Cammarota, Martín
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.01.2021
• Subjects: Animals; Avoidance Learning - drug effects; Avoidance Learning - physiology; Brain Hemisphere Functions; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - pharmacology; Brief Communication; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - metabolism; Extinction behavior; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Fear; Fear - drug effects; Fear - physiology; Hippocampus; Inhibition; Memory; Memory Consolidation - drug effects; Memory Consolidation - physiology; Mental Recall - drug effects; Mental Recall - physiology; Protein biosynthesis; Protein Kinase Inhibitors - pharmacology; Rapamycin; Recall; Recall (Psychology); Recombinant Proteins; Responses; Signal Transduction - drug effects; Signal Transduction - physiology; TOR protein; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism
• ISSN: 1072-0502; 1549-5485; 1549-5485
• DOI: 10.1101/lm.052068.120

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.