Bardy and Pallotto OB circuitry, by investigating whether the blockade of adult neurogenesis induced signiﬁcant changes in OB activity. By combining immunohistochemistry and patch-clamping techniques,the authors con- vincingly demonstrated that the number of functional GABAergic contacts received by mitral cells was much smaller in the AraC- treated mice than in the controls (Breton- Provencher, Figures 3 and 4). Surprisingly, despite the prevention of new neuron pro- duction over a period of 28 days, the overall number of granule cells was not modiﬁed (Breton-Provencher, Figures 2A,B). The authors of the study also demonstrated that the dendrite length and spine density of the neurons produced 1 month before AraC- treatment were not affected by the short- age of new neurons (Breton-Provencher, Figures 2C–E). It has been reported on several occasions that a rigorous selection of newly generated neurons for survival occurs around 2 weeks after their arrival in the OB (Mouret et al., 2008). This raises questions as to whether the blockade of new neuron production increases the survival of neurons generated just before AraC-treat- ment, thus accounting for the lack of change in the overall number of granule cells. This hypothesis could be tested experimentally by counting the number of neurons gen- erated shortly before the beginning of the treatment, and by showing that, 1 month later, a larger proportion of these neurons survived in AraC-treated than in saline- treated mice. The observation that mitral cells received about half as many spontane- ous GABAergic synaptic events in AraC- treated animals than in controls, despite the presence of similar numbers of gran- ule cells, is also rather surprising. The authors interpreted this result as a con- sequence of new neurons being prone to plastic excitatory centrifugal inputs unlike older pre-existing granule cells (Nissant et al., 2009). However, this conclusion is probably invalidated by the observa- tion that, even in the presence of TTX or Kynurenate, the frequency of IPSCs is signiﬁcantly lower in mitral cells of AraC- treated animals. Thus, to account for these results, it still need to be demonstrated that GABA synaptic release is much more efﬁcient in newly generated neurons than in older neurons, or that newly generated www.frontiersin.org What role for neurons generated in adults? neurons simply make far more functional the same function as the majority of OB GABAergic contacts. interneurons, which are presumably more The GABAergic interneurons in the gran- mature. Nevertheless, the challenge remains ule cell layer are known to synchronize the to ﬁnd a clear explanation of the mecha- activity of neurons in the mitral cell layer. nisms underlying the qualitative changes in The authors recorded local ﬁeld potentials network dynamics observed in the absence (LFPs) around the mitral cell layer of brain of newly generated neurons. slices from acutely treated mice and ana- Determining the value of new neurons to lyzed the gamma oscillations (20–80 Hz) the adult OB and DG is an important and evoked by electrical stimulation of the olfac- timely challenge in the ﬁeld of neurobiol- tory nerve (Breton-Provencher, Figure 5). ogy. The work of Breton-Provencher et al., Blocking the supply of new interneurons to together with recently published analyses of the adult OB did not affect the magnitude animals with impaired adult neurogenesis of the LFP oscillations, but tended to reduce provides us with precious food for thought their frequency. concerning the possible role of new neurons Similar results for oscillation frequen- (Imayoshi et al., 2008; Clelland et al., 2009; cies have been obtained for knockout Deng et al., 2009; Kitamura et al., 2009; mice lacking GABAA α1-subunit receptors Lazarini et al., 2009; Moreno et al., 2009; (Lagier et al., 2007). In α1-knockout mice, Valley et al., 2009). The contrasting results the remaining GABAA α3-subunit receptors obtained in different studies blocking adult in mitral cells were shown to mediate less neurogenesis and assessing olfactory behav- frequent spontaneous IPSCs of unchanged ior highlight the need for further investi- amplitude, but with a slower decay, result- gations to decipher the precise function of ing in slower gamma oscillations (Lagier adult neurogenesis for the sense of smell. It et al., 2007). However, it should be borne remains an open question whether newly in mind that Lagier et al. studied mice with generated interneurons in the OB play a constitutive KO, which may have affected roles different from those of their older, OB development or long-term compen- pre-existing counter-parts. We also cannot sation by other GABAergic mechanisms. rule out the possibility that newly gener- Nevertheless, the striking similarities in the ated neurons have different roles at different effects on oscillations between the studies stages of maturation. This process is prob- of Lagier and Breton-Provencher lead us ably even more complex than this, in that to think that the properties of the synaptic adult neurogenesis populates the OB with contacts established with mitral cells may several subtypes of interneurons, which differ between newly generated and pre- probably have different functions. However, existing neurons, particularly in terms of despite the many questions that remain post-synaptic GABAA receptor subunits, unresolved, the efforts of these authors to for example. If this hypothesis were cor- associate behavioral effects and changes in rect though, the kinetics of the spontane- OB circuit activity are remarkable, and will ous GABAergic events measured in the no doubt represent a major step toward a mitral cells of AraC-treated mice should greater understanding of the role of adult display a slower decay, similar to that for neurogenesis in olfaction. α3-subunit receptors. By contrast, another study showed that ACKNOWLEDGMENTS progressively blocking every subtype of We thank the members of the laboratory, GABAA receptor with various concentrations including, in particular, Mariana Alonso, of Gabazine reduced the amplitude of evoked Gabriel Lepousez, Françoise Lazarini, LFP oscillations, but not their frequen- Antoine Nissant, Gilles Gheusi and Pierre- cies (Bathellier et al., 2006). Bathelier et al. Marie Lledo, for fruitful discussions. This induced a broad blockade of post-synaptic work was supported by the Agence Nationale receptors, whereas Breton-Provencher et al. de la Recherche (ANR-2007 SEST-01411), eliminated a subpopulation of interneurons the Fondation pour la Recherche Médicale generated in adult animals. The contrast- “Equipe FRM”, the Groupe AG2R, the Ecole ing results obtained by Bathelier et al. and des Neurosciences de Paris (ENP), and a Breton-Provencher et al. again suggest that doctoral fellowship from Università Italo- newly generated neurons do not perform Francese (Progetto Vinci). March 2010 | Volume 4 | Article 24 | 3