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DCXCreERT2 – deciphering the role of adult neurogenesis

The birth and assimilation of new neurons in the adult brain – adult neurogenesis – occurs in two regions: the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ) along the walls of the lateral ventricles. Through a multi-stage process the newly born neurons become integrated into the existing hippocampal and Olfactory bulb (OB) circuitry. Several experimental setups have tried to elucidate the precise contribution of adult neurogenesis to overall brain function. Since these methods had some limitations that prevented the decoding of the process on its own, Lillian Garrett and her colleagues generated a transgenic mouse model (DCXCreERT2; DTA) that permits the inducible and reversible reduction of newly born neurons in neurogenic zones, with minimum interference in other brain areas and peripheral systems.

The activation of DTA results in a selective decrease of newly-born neurons in the hippocampal dentate gyrus and OB. To assess the function of these neurons, a series of different behavioral assays were conducted. These tests covered aspects of locomotor activity, exploration, anxiety-related behavior, simple spatial working memory, short-term olfactory learning in a social context and stress reactivity/depression-related behavior.

The scientists showed that the decrease of newly-born neurons 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 on switching off Cre recombinase. This demonstrated in addition the specificity of this effect. 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.

Lillian Garrett, Jingzhong Zhang, Annemarie Zimprich, Kristina M. Niedermeier, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabé de Angelis, Daniela Vogt Weisenhorn, Wolfgang Wurst and Sabine M. Hölter (2015). Conditional Reduction of Adult Born Doublecortin-Positive Neurons Reversibly Impairs Selective Behaviors. Front. Behav. Neurosci. 9:302.
doi: 10.3389/fnbeh.2015.00302