Altered Emotional and Locomotor Responses in Mice Deficient in the Transcription Factor CREM

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Nov 26

PMID 10570204

Citations 27

Authors

R Maldonado

C Smadja

C Mazzucchelli

P Sassone-Corsi

C Mazucchelli

Affiliations

Soon will be listed here.

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.

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References

Frank D, Greenberg M . CREB: a mediator of long-term memory from mollusks to mammals. Cell. 1994; 79(1):5-8. DOI: 10.1016/0092-8674(94)90394-8. View

Huang Y, Li X, Kandel E . cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase. Cell. 1994; 79(1):69-79. DOI: 10.1016/0092-8674(94)90401-4. View

Belvin M, Zhou H, Yin J . The Drosophila dCREB2 gene affects the circadian clock. Neuron. 1999; 22(4):777-87. PMC: 11772075. DOI: 10.1016/s0896-6273(00)80736-9. View

Monaco L, Foulkes N, Sassone-Corsi P . Pituitary follicle-stimulating hormone (FSH) induces CREM gene expression in Sertoli cells: involvement in long-term desensitization of the FSH receptor. Proc Natl Acad Sci U S A. 1995; 92(23):10673-7. PMC: 40674. DOI: 10.1073/pnas.92.23.10673. View

Foulkes N, Duval G, Sassone-Corsi P . Adaptive inducibility of CREM as transcriptional memory of circadian rhythms. Nature. 1996; 381(6577):83-5. DOI: 10.1038/381083a0. View

Mellstrom B, Naranjo J, Foulkes N, Lafarga M, Sassone-Corsi P . Transcriptional response to cAMP in brain: specific distribution and induction of CREM antagonists. Neuron. 1993; 10(4):655-65. DOI: 10.1016/0896-6273(93)90167-p. View

Fisher L . Corticotropin-releasing factor: endocrine and autonomic integration of responses to stress. Trends Pharmacol Sci. 1989; 10(5):189-93. DOI: 10.1016/0165-6147(89)90236-8. View

Yin J, Wallach J, Del Vecchio M, Wilder E, Zhou H, Quinn W . Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell. 1994; 79(1):49-58. DOI: 10.1016/0092-8674(94)90399-9. View

Alberini C, Ghirardi M, Metz R, Kandel E . C/EBP is an immediate-early gene required for the consolidation of long-term facilitation in Aplysia. Cell. 1994; 76(6):1099-114. DOI: 10.1016/0092-8674(94)90386-7. View

10.

Thiebot M, Soubrie P, Sanger D . Anxiogenic properties of beta-CCE and FG 7142: a review of promises and pitfalls. Psychopharmacology (Berl). 1988; 94(4):452-63. DOI: 10.1007/BF00212837. View

11.

Rodgers R, Lee C, Shepherd J . Effects of diazepam on behavioural and antinociceptive responses to the elevated plus-maze in male mice depend upon treatment regimen and prior maze experience. Psychopharmacology (Berl). 1992; 106(1):102-10. DOI: 10.1007/BF02253596. View

12.

Stehle J, Foulkes N, Molina C, Simonneaux V, Pevet P, Sassone-Corsi P . Adrenergic signals direct rhythmic expression of transcriptional repressor CREM in the pineal gland. Nature. 1993; 365(6444):314-20. DOI: 10.1038/365314a0. View

13.

Kornhauser J, Nelson D, Mayo K, Takahashi J . Photic and circadian regulation of c-fos gene expression in the hamster suprachiasmatic nucleus. Neuron. 1990; 5(2):127-34. DOI: 10.1016/0896-6273(90)90303-w. View

14.

Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva A . Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell. 1994; 79(1):59-68. DOI: 10.1016/0092-8674(94)90400-6. View

15.

Molina C, Foulkes N, Lalli E, Sassone-Corsi P . Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor. Cell. 1993; 75(5):875-86. DOI: 10.1016/0092-8674(93)90532-u. View

16.

Kokkinidis L, Anisman H . Dissociation of the effects of scopolamine and d-amphetamine on a spontaneous alternation task. Pharmacol Biochem Behav. 1976; 5(3):293-7. DOI: 10.1016/0091-3057(76)90081-2. View

17.

Lister R . The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berl). 1987; 92(2):180-5. DOI: 10.1007/BF00177912. View

18.

Foulkes N, Borjigin J, Snyder S, Sassone-Corsi P . Rhythmic transcription: the molecular basis of circadian melatonin synthesis. Trends Neurosci. 1997; 20(10):487-92. DOI: 10.1016/s0166-2236(97)01109-0. View

19.

Balsalobre A, Damiola F, Schibler U . A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell. 1998; 93(6):929-37. DOI: 10.1016/s0092-8674(00)81199-x. View

20.

Kokkinidis L, Anisman H . Circling behavior following systemic d-amphetamine administration: potential noradrenergic and dopaminergic involvement. Psychopharmacology (Berl). 1979; 64(1):45-54. DOI: 10.1007/BF00427344. View