title: Conditional Reduction of Adult Born Doublecortin-Positive Neurons Reversibly Impairs Selective Behaviors.
abstract: Adult neurogenesis occurs in the adult mammalian subventricular zone (SVZ) along the walls of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus. While a burgeoning body of research implicates adult neurogenesis in olfactory bulb (OB)- and hippocampal-related behaviors, the precise function continues to elude. To further assess the behavioral importance of adult neurogenesis, we herein generated a novel inducible transgenic mouse model of adult neurogenesis reduction where mice with CreER(T2) under doublecortin (DCX) promoter control were crossed with mice where diphtheria toxin A (DTA) was driven by the Rosa26 promoter. Activation of DTA, through the administration of tamoxifen (TAM), results in a specific reduction of DCX+ immature neurons in both the hippocampal dentate gyrus and OB. We show that the decrease of DCX+ cells causes impaired social discrimination ability in both young adult (from 3 months) and middle aged (from 10 months) mice. Furthermore, these animals showed an age-independent altered coping behavior in the Forced Swim Test without clear changes in anxiety-related behavior. Notably, these behavior changes were reversible on repopulating the neurogenic zones with DCX+ cells on cessation of the TAM treatment, demonstrating the specificity of this effect. Overall, these results support the notion that adult neurogenesis plays a role in social memory and in stress coping but not necessarily in anxiety-related behavior.
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany ; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany.
authors.forename: Lillian
authors.initials: L
authors.lastname: Garrett
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany ; Max Delbrück Zentrum für Molekulare Medizin Berlin, Germany.
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany ; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Zimprich
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany ; Technische Universität München Freising-Weihenstephan, Germany.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Niedermeier
authors.affiliation: German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.affiliation: German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Gailus-Durner
authors.affiliation: German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany ; Technische Universität München Freising-Weihenstephan, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vogt Weisenhorn
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany ; Technische Universität München Freising-Weihenstephan, Germany ; Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE) Munich, Germany ; Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-Universität München Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany ; German Mouse Clinic, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany.
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
keywords: doublecortin; emotionality; mice; neurogenesis; social discrimination