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Related Experiment Video

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Trace Fear Conditioning in Mice
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Input associativity underlies fear memory renewal.

Wei-Guang Li1, Yan-Jiao Wu1, Xue Gu1

  • 1Center for Brain Science of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

National Science Review
|October 25, 2021
PubMed
Summary

Synaptic associativity between auditory cortex and ventral hippocampus inputs to the lateral amygdala drives fear renewal. This neural mechanism reactivates learning-associated ensembles, underlying context-dependent memory relapse.

Keywords:
auditory cortexfear renewalinput associativitylateral amygdalalong-term potentiationmemory ensemblesventral hippocampus

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Area of Science:

  • Neuroscience
  • Learning and Memory
  • Synaptic Plasticity

Background:

  • Synaptic associativity, a key mechanism in Hebbian plasticity, is crucial for associative learning.
  • The role of synaptic associativity in context-dependent memory relapse, specifically fear renewal, remains largely unexplored.

Purpose of the Study:

  • To investigate the involvement of synaptic associativity in fear renewal.
  • To identify the neural pathways and mechanisms underlying context-dependent fear memory relapse.

Main Methods:

  • Auditory fear conditioning paradigm in mice.
  • Electrophysiological recordings and optogenetic manipulations in the lateral amygdala (LA).
  • Assessment of synaptic strength changes in auditory cortex (ACx) to LA and ventral hippocampus (vHPC) to LA pathways.

Main Results:

  • Fear renewal was found to be dependent on the associativity between ACx and vHPC inputs converging onto the LA.
  • Fear renewal enhanced synaptic strengths in both ACx-LA and previously uncharacterized vHPC-LA monosynaptic inputs.
  • Inactivation of either pathway abolished fear renewal, while optogenetic activation of their input associativity in the LA successfully recapitulated fear renewal.

Conclusions:

  • Input associativity within the lateral amygdala is a critical neural substrate for fear memory renewal.
  • This study elucidates a cellular mechanism linking synaptic plasticity to the context-dependent relapse of extinguished fear memories.