Frontiers in Behavioral Neuroscience (Nov 2015)

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

  • 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,
  • Sabine M Hölter

DOI
https://doi.org/10.3389/fnbeh.2015.00302
Journal volume & issue
Vol. 9

Abstract

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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.

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