title: Neurobehavioral basis of the impaired nurturing in mice lacking the immediate early gene FosB.
abstract: 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.
authors.affiliation: Kuroda Research Unit for Affiliative Social Behavior, RIKEN Brain Science Institute, Saitama 351-0198, Japan. asbcontact@brain.riken.jp
authors.forename: Kumi O
authors.initials: KO
authors.lastname: Kuroda
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
authors.forename: Noriko
authors.initials: N
authors.lastname: Uetani
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Kato
mesh_terms: 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
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016760:Proto-Oncogene Proteins c-fos; D006854:Hydrocortisone