mTOR inhibition impairs extinction memory reconsolidation

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• Fear extinction memory is crucial for adaptive behavior.
• Memory reconsolidation is a process where recalled memories become labile and require stabilization.
• Hippocampal brain-derived neurotrophic factor (BDNF) is implicated in memory reconsolidation.

Purpose of the Study:

• To investigate the role of mammalian target of rapamycin (mTOR) signaling in the reconsolidation of fear-motivated avoidance extinction memory.
• To determine the relationship between mTOR and BDNF in this process.

Main Methods:

• Activation of mTOR in the dorsal CA1 region of the hippocampus during extinction memory recall was assessed.
• The effect of post-recall inhibition of hippocampal mTOR on memory persistence was evaluated.
• The influence of co-administering recombinant BDNF with hippocampal mTOR inhibition was examined.

Main Results:

• Extinction memory recall activates mTOR in the dorsal CA1 hippocampus.
• Inhibiting mTOR after recall impaired avoidance extinction memory persistence and reinstated the aversive response.
• Recombinant BDNF administration counteracted the behavioral effects of hippocampal mTOR inhibition.

Conclusions:

• mTOR signaling is essential for the reconsolidation of fear-motivated avoidance extinction memory.
• BDNF appears to act downstream of mTOR in a protein synthesis-independent manner to stabilize reactivated extinction memory traces.