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Updated: May 15, 2026

Protocol for Studying Extinction of Conditioned Fear in Naturally Cycling Female Rats
09:07

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Published on: February 23, 2015

Behavioral tagging of extinction learning.

Jociane de Carvalho Myskiw1, Fernando Benetti, Iván Izquierdo

  • 1National institute of Translational Neuroscience, National Research Council of Brazil, and Memory Center, Brain Institute, Pontifical Catholic University of Rio Grande do Sul, 90610-000 Porto Alegre, RS, Brazil. jociane_carvalho@hotmail.com

Proceedings of the National Academy of Sciences of the United States of America
|January 2, 2013
PubMed
Summary
This summary is machine-generated.

Novel environments enhance fear extinction memory in rats by activating protein synthesis in the hippocampus. This process, similar to synaptic tagging, strengthens fear memory consolidation.

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Area of Science:

  • Neuroscience
  • Behavioral Neuroscience
  • Molecular Neuroscience

Background:

  • Contextual fear extinction is crucial for treating anxiety disorders.
  • Environmental novelty is known to influence memory consolidation processes.
  • Synaptic plasticity mechanisms underlie learning and memory formation.

Purpose of the Study:

  • To investigate the role of environmental novelty in modulating contextual fear extinction in rats.
  • To elucidate the molecular mechanisms, including protein synthesis and gene expression, involved in this modulation.
  • To explore the involvement of the hippocampus and amygdala in novelty-enhanced fear extinction.

Main Methods:

  • Rats underwent contextual fear conditioning followed by extinction training.
  • Exposure to a novel environment was administered before or after extinction.
  • Protein synthesis inhibitors (anisomycin, rapamycin) and a gene expression blocker were administered into the hippocampus or amygdala.
  • Behavioral testing assessed fear extinction recall.

Main Results:

  • Exposure to a novel environment significantly enhanced contextual fear extinction.
  • This enhancement was blocked by hippocampal administration of protein synthesis inhibitors given after novelty or extinction.
  • Gene expression blockers impaired the effect when given after novelty exposure.
  • The amygdala was not involved in mediating this effect.

Conclusions:

  • Environmental novelty enhances contextual fear extinction through a protein synthesis-dependent mechanism in the hippocampus.
  • The findings support a synaptic tagging and capture model, where novelty provides plasticity-related proteins captured by extinction-induced synaptic tags.
  • This suggests that novelty can strengthen the neural circuits involved in fear memory suppression.