GENERAL COMMENTARY published: 26 March 2010 doi: 10.3389/fnnes.2010.00002 What happens to olfaction without adult neurogenesis? Cedric Bardy1* and Marta Pallotto1,2 1 Laboratory for Perception and Memory, Department of Neuroscience, Centre National de la Recherche Scientiﬁque, Institut Pasteur, Paris, France 2 Department of Anatomy, Pharmacology and Forensic Medicine, National Institute of Neuroscience-Italy, University ofTurin,Turin, Italy *Correspondence: e-mail: cedbardy@pasteur.fr A commentary on Interneurons produced in adulthood are required for the normal functioning of the olfactory bulb network and for the execu- tion of selected olfactory behaviors. by Breton-Provencher, V., Lemasson, M., Peralta, M.R. III, Saghatelyan, A. (2009) J. Neurosci. 29(48), 15245–15257. Constitutive neurogenesis clearly occurs within the adult central nervous system of almost all mammals. This process gener- ates new neurons in at least two areas of the brain: the olfactory bulb (OB) and the dentate gyrus (DG) of the hippocampus. However, it remains unknown why new neurons speciﬁcally populate those two neural structures rather than other areas. In empirical experiments, adult neurogen- esis was impaired and the consequences of this impairment for the neural circuitry and behavior of animals were investigated with a view to determining the role of new neurons in the adult brain. In the December issue of the Journal of Neuroscience, Breton-Provencher et al. addressed this issue, by using drugs to estab- lish a transient blockade of adult neuro- genesis and combining several techniques to evaluate the consequences of this block- ade for OB circuits and particular types of behavior. Here, we summarize and discuss some of their ﬁndings in light of other recently published data. for 28 days. The neurogenic niches of the neural precursors that migrate to the OB circuit are located in the wall of the LV, in the subventricular zone (SVZ). AraC infu- sion into the LV is thus a highly effective method for decreasing OB neurogenesis. After AraC-treatment, the authors reported a 75% decrease in Dcx levels on western blots, this protein being a marker for immature neuroblasts; they also showed an almost complete absence of Dcx immunos- taining in the OB (see Breton-Provencher, Figure 1A,B). This infusion also affected neurogenesis in the DG, but to lesser extent (−50%; see Breton-Provencher, Figure 1C). Different methods for blocking adult neu- rogenesis may have different effects on the proportion of new neurons in the OB or DG (see Table 1). Focused irradiation tends to be more speciﬁc than pharmacological methods (Clelland et al., 2009; Lazarini et al., 2009; Valley et al., 2009). Various genetic approaches have also been used to decrease the size of newly generated neuron population in a transient manner (Imayoshi et al., 2008; Deng et al., 2009). However, these genetic approaches have, to date, proved even less speciﬁc than irradia- tion or pharmacological approaches, affect- ing adult neurogenesis to similar extents in the OB and DG. Adult neurogenesis may serve different functions in these two structures, but may also underlie common patterns of behavior, such as exploratory or learning behavior. It is therefore impor- tant to check the speciﬁcity of the blockade BLOCKING ADULT NEUROGENESIS of adult neurogenesis in both neurogenic Several experimental approaches have areas, particularly when trying to deter- been developed for blocking adult neuro- mine the contribution of new neurons to genesis. Most were inspired by tools origi- speciﬁc types of behavior. nally designed to reduce cell proliferation in the treatment of cancers. For example, INFLUENCE OF THE BLOCKADE OF cytosine-β-d-arabinofuranoside (AraC) ADULT NEUROGENESIS ON is an antimitotic drug used in chemo- OLFACTORY BEHAVIOR therapy to treat hematological malignan- Breton-Provencher et al. investigated the cies in humans. Breton-Provencher et al. role of neurons generated in adult animals, used osmotic pumps to infuse AraC into in several behavioral tests.They ﬁrst checked the lateral ventricle (LV) of adult mice that the effects observed were speciﬁcally www.frontiersin.org due to the ablation of new neurons in the OB, by demonstrating that AraC-treat- ment had no effect on the performance of the mice in diverse activities that might indirectly inﬂuence their performance in speciﬁc olfactory tests (Breton-Provencher, Figure 6). In particular, they reported that AraC-treated mice performed well in exer- cises involving spontaneous locomotor activity, object exploration and recogni- tion. They also tested the treated mice in tail suspension and novelty suppressed feed- ing tests, to demonstrate that the treatment did not induce anxious behavior (see also (Kitamura et al., 2009; Moreno et al., 2009). These controls were necessary and entirely appropriate. Nevertheless, the role of the hippocampus in olfactory behavior can- not be excluded (Gourevitch et al., 2010). In our opinion, for the complete exclusion of possible effects of a partial blockade of DG neurogenesis on the olfactory tests, a straightforward control would have been to evaluate the olfactory behavior of the mice whilst impairing DG neurogenesis alone. The olfactory behavior experiments showed that continuous neurogenesis in the OB was required only for certain non rein- forced olfactory tasks (Breton-Provencher, Figure 7). The authors showed that AraC- treated mice had higher detection thresh- olds for odorants. The authors therefore used high odor concentrations for their subsequent evaluation of olfactory memory in the mice. They found that brief, non rein- forced exposure to an odor was remembered for only 30 min by the AraC-treated mice, whereas the same odor was remembered for at least 2 h by the saline-treated mice. Finally, the authors assessed the long-term associative olfactory memory of the mice with impaired adult neurogenesis. In partic- ular, they tested the capacity of the mice to remember an odor associated with a reward (food) and to discriminate this odor from an odor not associated with a reward. They reported that 24 h or 1 week after learning, mice with impaired adult neurogenesis March 2010 | Volume 4 | Article 24 | 1