Neurobehavioral basis of the impaired nurturing in mice lacking the immediate early gene FosB.
The transcription factor FosB is induced in neurons of the medial preoptic area (MPOA) during parenting, through activation of the extracellular signal-regulated kinase (ERK). FosB mutant (-/-) postpartum mice and virgin mice that are exposed to pups show defective nurturing behavior. The FosB (-/-) MPOA fails to fully up-regulate SPRY1 and Rad, the feedback regulators of ERK and calcium signaling, respectively. Here we studied FosB function by examining the gene expression profiles and the behavioral characteristics of FosB (-/-) mice. We found that FosB (-/|-) mice exhibited not only decreased parenting but also decreased infanticide compared with (+/) littermates. We then performed gene expression analysis in the MPOA of FosB (-/-) mice compared with the wild-type littermates. We found up-regulation of glial fibrillary acidic protein (GFAP), C4, and Ela1 mRNA in the MPOA of FosB (-/-) mice; all of these gene products were implicated in general neuropathological conditions. Immunohistochemical analysis showed that up-regulation of GFAP was not restricted to MPOA but extended throughout the forebrain, including the cerebral cortex and striatum. Such pervasive GFAP up-regulation suggested that FosB (-/-) mice might have other behavioral abnormalities than nurturing. Indeed, these mice showed a clear alteration in emotionality, detected by the acoustic startle, elevated plus maze, and passive avoidance tests. These results suggest that FosB (-/-) mice have broader neurobehavioral dysfunctions, with which the nurturing defect might share the common mechanism.
Kuroda
Kumi O
KO
Kuroda Research Unit for Affiliative Social Behavior, RIKEN Brain Science Institute, Saitama 351-0198, Japan. asbcontact@brain.riken.jp
Meaney
Michael J
MJ
Uetani
Noriko
N
Kato
Tadafumi
T
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D005260:Female; D016762:Genes, fos / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008425:Maternal Behavior / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009490:Neurosecretory Systems / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011301:Preoptic Area / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics / Q000502:physiology; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
D005904:Glial Fibrillary Acidic Protein; D016760:Proto-Oncogene Proteins c-fos; D006854:Hydrocortisone