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Cyclic AMP response element-binding protein is required for normal maternal nurturing behavior.

S-H Jin¹, J A Blendy, S A Thomas

¹Department of Pharmacology, 103 John Morgan Building, 3620 Hamilton Walk, University of Pennsylvania, Philadelphia, PA 19104-6084, USA.

|May 17, 2005

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Cyclic AMP response element-binding protein (CREB) is crucial for maternal nurturing behavior in mice. Disrupting CREB impairs pup retrieval and survival, but not FosB expression, indicating a distinct role in maternal care.

Area of Science:

Neuroscience
Behavioral Genetics
Molecular Biology

Background:

FosB and adrenergic signaling are vital for maternal nurturing behavior.
Previous studies showed that disruptions in FosB or dopamine beta-hydroxylase impair maternal care.
The role of cyclic AMP response element-binding protein (CREB) as a potential intermediary was investigated.

Purpose of the Study:

To investigate the role of CREB in maternal nurturing behavior.
To determine if CREB shares a signaling pathway with FosB and adrenergic signaling in maternal care.
To examine the relationship between CREB, FosB, and pup-induced FosB expression.

Main Methods:

Analysis of mice with targeted disruptions of CREB (Creb-alphaDelta-/-) and CREM genes.
Cross-fostering experiments to assess maternal care capabilities.

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Immunostaining for phospho-CREB in the medial preoptic area of the hypothalamus.

Measurement of FosB expression in response to pup exposure.

Main Results:

Mice lacking major CREB isoforms (Creb-alphaDelta-/-) exhibited significant neonate mortality and impaired pup retrieval in virgin females.
CREB deficiency did not affect FosB expression or induction in response to pup exposure.
Phospho-CREB levels increased in the medial preoptic area upon pup exposure in wild-type mice.
No maternal behavior phenotype was observed in mice with a null mutation of the CREM gene.

Conclusions:

CREB plays a critical role in maternal nurturing behavior, independent of FosB.
CREB signaling is essential for the survival and care of neonates.
The findings implicate CREB as a key regulator in the neural circuits governing maternal behavior.