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Updated: Jul 31, 2026
07:02
Trace Fear Conditioning in Mice
Published on: March 20, 2014
Long-term memory is facilitated by cAMP response element-binding protein overexpression in the amygdala
S A Josselyn1, C Shi, W A Carlezon
1Department of Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center, New Haven, Connecticut 06508, USA. sjosselyn@mednet.ucla.edu
Summary
Spaced training enhances long-term memory (LTM) more than massed training. Increasing cAMP response element-binding protein (CREB) in the amygdala boosts LTM after massed fear conditioning, suggesting CREB acts as a molecular switch.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Science
Background:
- Long-term memory (LTM) formation requires de novo protein synthesis.
- Spaced training is generally more effective than massed training for LTM.
- cAMP response element-binding protein (CREB) is a potential regulator of LTM.
Purpose of the Study:
- To investigate the role of CREB in LTM formation during fear conditioning.
- To determine if CREB levels in the amygdala influence LTM after massed training.
Main Methods:
- Rats received either spaced or massed fear conditioning.
- CREB levels in the basolateral amygdala were manipulated using viral vectors.
- LTM was assessed using fear-potentiated startle.
Main Results:
- Massed fear conditioning resulted in weak or no LTM compared to spaced training.
- Overexpression of CREB in the basolateral amygdala enhanced LTM after massed training.
- The effect of CREB was specific to biochemistry, anatomy, time course, and training procedure.
Conclusions:
- CREB activity in the amygdala is crucial for LTM formation in fear conditioning.
- CREB acts as a molecular switch regulating LTM consolidation.
- Targeting CREB may offer therapeutic strategies for memory disorders.
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