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Conditional reduction of adult born doublecortin-positive neurons reversibly impairs selective behaviours

By Lillian eGarrett, Jingzhong eZhang, Annemarie eZimprich, Kristina M Niedermeier, Kristina M Niedermeier, Helmut eFuchs, Valerie eGailus-Durner, Martin eHrabe de Angelis, Martin eHrabe de Angelis, Daniela eVogt-Weisenhorn, Wolfgang eWurst, Wolfgang eWurst, Wolfgang eWurst, Wolfgang eWurst and Sabine M Hölter


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 CreERT2 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 (from 10 months) aged 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 tamoxifen 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

Topics: Mice, Neurogenesis, doublecortin, emotionality, social discrimination, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Publisher: Frontiers Media S.A.
Year: 2015
DOI identifier: 10.3389/fnbeh.2015.00302
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