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

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Item Type:Article
Title:Conditional reduction of adult born doublecortin-positive neurons reversibly impairs selective behaviors
Creators Name:Garrett, L. and Zhang, J. and Zimprich, A. and Niedermeier, K.M. and Fuchs, H. and Gailus-Durner, V. and Hrabe de Angelis, M. and Vogt Weisenhorn, D. and Wurst, W. and Hoelter, S.M.
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.
Keywords:Neurogenesis, Doublecortin, Social Discrimination, Emotionality, Animals, Mice
Source:Frontiers in Behavioral Neuroscience
ISSN:1662-5153
Publisher:Frontiers Research Foundation (Switzerland)
Volume:9
Page Range:302
Date:12 November 2015
Official Publication:https://doi.org/10.3389/fnbeh.2015.00302
PubMed:View item in PubMed

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