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Updated: Jun 22, 2026
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Trace Fear Conditioning in Mice
Published on: March 20, 2014
A cholinergic-dependent role for the entorhinal cortex in trace fear conditioning
Frederic Esclassan1, Etienne Coutureau, Georges Di Scala
1Centre National de la Recherche Scientifique, Centre de Neurosciences Intégratives et Cognitives, Unité Mixte de Recherche (UMR) 5228, Talence, France.
Summary
The entorhinal cortex (EC) is crucial for learning fear through trace conditioning, where a tone CS must be remembered across a 30-second interval. Blocking M1 receptors in the EC during acquisition impairs this learning.
Area of Science:
- Neuroscience
- Cognitive Neuroscience
- Behavioral Neuroscience
Background:
- Trace conditioning models higher cognitive functions in associative learning.
- Cortical areas and the hippocampal formation are essential for associating temporally separated events.
- Mechanisms bridging the trace interval in trace conditioning remain unclear.
Purpose of the Study:
- To investigate the entorhinal cortex (EC) role in acquiring fear conditioning under a trace-30 s protocol.
- To elucidate the neural mechanisms underlying the trace interval in associative learning.
Main Methods:
- Fear conditioning in rats using a trace-30 s protocol.
- Pretraining neurotoxic lesions of the entorhinal cortex (EC).
- Local cholinergic deafferentation of the EC using 192-IgG-saporin.
- Pretraining local blockade of EC muscarinic receptors with pirenzepine.
Main Results:
- EC lesions selectively impaired trace-conditioned fear, not delay-conditioned fear.
- Cholinergic deafferentation of the EC did not replicate the deficit.
- Blockade of EC M1 receptors during acquisition dose-dependently impaired trace-conditioned fear.
- Post-conditioning M1 receptor blockade had no effect on fear responses.
Conclusions:
- The entorhinal cortex (EC) is necessary for acquiring trace-conditioned fear.
- Acetylcholine-dependent persistent activity in the EC is required to bridge the trace interval.
- The EC functions as a short-term stimulus buffer during trace conditioning acquisition.
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