MAPK Signaling Determines Anxiety in the Juvenile Mouse Brain but Depression-Like Behavior in Adults

  • MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice, which exhibit protein depletion in principle forebrain neurons, enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inducible or constitutive inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In juvenile, constitutive mutants we found no alteration of GABAergic neurotransmission but MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice, which exhibit protein depletion in principle forebrain neurons, enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inducible or constitutive inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In juvenile, constitutive mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype. Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as a new valuable approach, allowing it to discriminate between gene function in the adult and the developing postnatal brain.show moreshow less

Download full text files

Export metadata

  • Export Bibtex
  • Export RIS

Additional Services

Share in Twitter Search Google Scholar
Metadaten
Author:Benedikt Wefers, Christiane Hitz, Sabine M. Hölter, Dietrich Trümbach, Jens Hansen, Peter Weber, Benno Pütz, Jan M. Deussing, Martin Hrabé de Angelis, Till Roenneberg, Fang Zheng, Christian Alzheimer, Alcino Silva, Wolfgang Wurst, Ralf Kühn
URN:urn:nbn:de:bvb:29-opus-37034
Document Type:Article
Language:English
Date of Publication (online):2012/10/30
Publishing Institution:Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Release Date:2012/10/30
SWD-Keyword:-
Original publication:PLoS ONE 7.4 (2012): 29.10.2012 <http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0035035>
Institutes:Medizinische Fakultät / Medizinische Fakultät -ohne weitere Spezifikation-
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Collections:Universität Erlangen-Nürnberg / Open Access Artikel ohne Förderung / Open Access Artikel ohne Förderung 2012

$Rev: 13581 $