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Related Experiment Video

Updated: May 5, 2026

Trace Fear Conditioning in Mice
07:02

Trace Fear Conditioning in Mice

Published on: March 20, 2014

33.2K

Developing and validating trace fear conditioning protocols in C57BL/6 mice.

Michael A Burman1, Cassandra A Simmons1, Miles Hughes1

  • 1Department of Psychology, Center for Excellence in the Neurosciences, University of New England, United States.

Journal of Neuroscience Methods
|November 26, 2013
PubMed
Summary

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This study developed a reliable trace fear conditioning protocol for mice, demonstrating its dependence on the hippocampus. This new method is crucial for future research on fear, anxiety, and memory in genetically modified mouse models.

Area of Science:

  • Neuroscience
  • Behavioral Science

Background:

  • Fear conditioning is a key model for studying fear, anxiety, and memory.
  • While delay conditioning primarily involves the amygdala, trace and contextual conditioning require both the amygdala and hippocampus.
  • These paradigms, traditionally used in rats, are increasingly applied to mice.

Purpose of the Study:

  • To develop and validate a robust trace fear conditioning protocol for C57BL/6N mice.
  • To ensure the protocol accurately assesses hippocampus-dependent learning, differentiating it from non-associative fear responses.
  • To establish a reliable method for future studies involving genetically modified mice.

Main Methods:

  • Modified an initial trace conditioning protocol by decreasing tone intensity and increasing the inter-trial interval.
Keywords:
Associative learningBehaviorConditioningFearMouse

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  • Included an unpaired stimulus control group to differentiate associative learning from non-associative freezing.
  • Utilized hippocampus lesions to confirm the neural basis of the observed trace conditioning.

    • Main Results:

    • The refined protocol successfully induced significant trace conditioned freezing in mice.
    • Trace conditioned freezing was demonstrably greater than in the unpaired control group.
    • Hippocampus lesions abolished the learned trace conditioned freezing, confirming its dependence on this structure.

    Conclusions:

    • The developed trace fear conditioning protocol is effective and hippocampus-dependent in C57BL/6N mice.
    • This validated protocol addresses limitations in previous mouse models, particularly the lack of appropriate control groups.
    • It provides a valuable tool for future research on the neurobiology of fear and memory, especially in genetically modified mouse lines.