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Altered emotional and locomotor responses in mice deficient in the transcription factor CREM
R Maldonado1, C Smadja, C Mazzucchelli
1Département de Pharmacologie Moléculaire et Structurale, Institut National de la Santé et de la Recherche Médicale U266, France. rafael.maldonado@cexs.upf.es
Abstract:
Various transcription factors act as nuclear effectors of the cAMP-dependent signaling pathway. These are the products of three genes in the mouse, CREB, CRE modulator (CREM), and ATF-1. CREM proteins are thought to play important roles within the hypothalamic-pituitary axis and in the control of rhythmic functions in the pineal gland. We have generated CREM-mutant mice and investigated their response in a variety of behavioral tests. CREM-null mice show a drastic increase in locomotion. In contrast to normal mice, the CREM-deficient mice show equal locomotor activity during the circadian cycle. The anatomy of the hypothalamic suprachiasmatic nuclei, the center of the endogenous pacemaker, is normal in mutant mice. Remarkably, CREM mutant mice also elicit a different emotional state, revealed by a lower anxiety in two different behavioral models, but they preserve the conditioned reactiveness to stress. These results demonstrate the high degree of functional specificity of each cAMP-responsive transcription factor in behavioral control.
Insights
Mice lacking the CREM gene exhibit altered circadian rhythms and reduced anxiety. This highlights the specific role of cAMP-responsive transcription factors in controlling behavior.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- cAMP-dependent signaling pathway involves transcription factors like CREB, CREM, and ATF-1.
- CREM proteins are implicated in the hypothalamic-pituitary axis and pineal gland rhythmic functions.
Purpose of the Study:
- To investigate the behavioral responses of CREM-mutant mice.
- To understand the functional specificity of cAMP-responsive transcription factors in behavioral control.
Main Methods:
- Generation of CREM-mutant mice.
- Behavioral testing, including locomotion and anxiety models.
- Analysis of circadian locomotor activity and stress reactivity.
Main Results:
- CREM-null mice display significantly increased locomotion.
- Mutant mice exhibit normalized locomotor activity across the circadian cycle.
- CREM deficiency leads to reduced anxiety but preserved stress-induced responses.
Conclusions:
- CREM plays a crucial role in regulating locomotor activity and circadian rhythms.
- CREM influences emotional states, specifically anxiety levels.
- These findings underscore the distinct functional roles of cAMP-responsive transcription factors in behavior.