Commentary: “Posttraining ablation of adult-generated olfactory granule cells degrades odor-reward memories”

Citation: Vangeneugden J, Mazo C and Lepousez G (2015) Commentary: " Posttraining ablation of adult-generated olfactory granule cells degrades odor-reward memories. " Front. Neurosci. 9:110. In the adult brain, hippocampus and olfactory bulb retain the remarkable capacity of generating new neurons and implementing them into existing neural circuitry. This phenomenon, adult neu-rogenesis, results from the presence of specific neurogenic zones, i.e., the sub-granular zone of the dentate gyrus and the sub-ventricular zone (SVZ). Within these regions, new immature neurons are continuously produced and then migrate out to their respective target circuits, differentiating either into glutamatergic neurons (dentate gyrus) or into mostly GABAergic interneurons called granule cells in the olfactory bulb. As a result, the production of new neurons throughout life is recognized as an extreme form of plasticity. The functional impact of recruiting newly-formed neurons on circuit functioning and their associated behaviors is a matter of intense investigation. In the olfactory bulb, loss-of-function experiments have led to incongruent results regarding the role of newly-generated olfactory granule cells (OGC) in learning and memory. Previous method-ologies to experimentally reduce neurogenesis consisted of administration of anti-mitotic or anti-proliferative drugs (1), focal irradiation (2) or use of genetic knockout mice (3). These studies have provided much insight, however are affected by (1) a-specificity leading to off-target effects such as targeting all proliferating cells within the hippocampus and the olfactory bulb with limited possibility to restrict this ablation in time, by (2) strong side neuro-inflammatory responses and by (3) brain-wide compensatory mechanisms, respectively. To circumvent some of these issues, Arruda-Carvalho et al. (2014) investigated the functional significance of adult-born OGC by employing a powerful and selective " tag-and-ablate " genetic strategy while measuring the impact on behavior. To generate a conditional ablation of adult-born neurons, they crossed a line expressing a CRE-recombinase-dependent diphteria-toxine receptor (DTR) transgene with a strain carrying a tamoxifen-inducible CRE-recombinase cassette preferentially in SVZ Nestin-positive cells, that is to say preferentially in SVZ neural precursor cells compared to dentate gyrus precursor cells. In these double transgenic mice, short exposure to tamoxifen (TAM) triggers the expression of DTR in the neural stem cells and all their progeny. Following this tagging, a subsequent diphteria toxin injection specifically kills the tagged cells born after TAM injection, however the effectiveness of the ablation technique was not examined directly, via e.g. BrdU/NeuN or BrdU/Dcx staining. It is noteworthy that the administration of TAM induces a permanent recombination …