Glarne Cyra tnemo published: 06 August 2012 doi: 10.3389/fnins.2012.00117 Brain control of olfaction via top-down regulation on adult neurogenesis Livio Oboti1* and Jean-Claude Platel 2 1 Department of Physiology, University of Saarland, Homburg, Germany 2 Grenoble Institute des Neurosciences U836, Université Joseph Fourier Grenoble, Grenoble, France *Correspondence: l.oboti@mx.uni-saarland.de Edited by: Joseph LoTurco, University of Connecticut, USA Reviewed by: Joanne C. Conover, University of Connecticut, USA Ottorino Belluzzi, University of Ferrara, Italy A commentary on Action of the noradrenergic system on adult-born cells is required for olfactory learning in mice by Moreno, M. M., Bath, K., Kuczewski, N., Sacquet, J., Didier, A., and Mandairon, N. (2012). J. Neurosci. 32, 3748–3758. According to Dr. Pangloss (Voltaire, 1759), noses were made to wear glasses, legs were meant to wear pants, and olfactory bulb newborn granule cells (GCs) to improve olfaction. While the first two hypotheses have been rejected almost unanimously, the latter may not be far from the truth, yet the reason has not been defined. Initially, this assumption has emerged by revealing the physiological properties of newborn GCs: they are highly excitable and preferentially involved in events of synaptic plasticity (Nissant et al., 2009), they selectively respond to experienced stimuli (Magavi et al., 2005), their ablation impairs olfactory learning and memory (see for example Mouret et al., 2008; Moreno et al., 2009; Oboti et al., 2011) while their specific stimulation facilitates these pro- cesses (Alonso et al., 2012). Inspired by the definition of the receptor neuron-to-mitral cell labeled-line as the essential functional unit of the OB circuitry, most functional studies have analyzed the problem under a paradigm dictated by this centripetal logic: a manipulation in the periphery (environ- ment, or local OB circuitry) is used to test the central brain function. However, GCs connectivity is not limited to local neuronal networks (interneurons and mitral cells). These cells also receive centrifugal inputs onto their basal and proximal dendritic www.frontiersin.org domains and show early synaptic responses to glutamate before the establishment of synaptic connections with mitral cells at the more distal portions of their dendritic arbors (Panzanelli et al., 2009). In addition, olfactory deprivation differentially affects spine density in the distal and proximal den- dritic domains, where respectively centrip- etal and centrifugal synaptic connections take place (Kelsch et al., 2009). Hence, the role of central brain activity is exceedingly likely to affect the fate of developing GCs, but the mechanisms of this effect have yet to be elucidated. Surprisingly, only a few reports have aimed to do so (Bauer et al., 2003; Cooper-Kuhn et al., 2004; Veyrac et al., 2005, 2009) and, although focusing on the local OB reveals why younger neurons may be preferable to older ones, the mecha- nisms by which the brain makes this choice can not be fully clarified without consider- ing its feedback modulatory activity. Moreno et al. (2012) have recently shed new light on this issue and analyzed the interaction between centrifugal innerva- tion and plasticity in the olfactory bulb in a sensory context meaningful for both. The authors investigated the involvement of the noradrenergic signaling in the olfac- tory perceptual learning, a form of learning in which previous experience like olfactory habituation allows discrimination between perceptually similar odorants. They showed that blocking the noradr- energic system during olfactory enrichment abolishes its positive effects on olfactory dis- criminatory ability while the stimulation of the noradrenergic system alone results in better performances in the discriminatory task. To complete the picture of the involve- ment of the noradrenergic system, they showed that olfactory enrichment induced a higher activity in the locus coeruleus, the source of noradrenergic fibers in the brain. Previous reports revealed that per- ceptual learning requires the incorporation and activation of newborn GCs (Moreno et al., 2009). Consistently, treatment with an agonist of the noradrenergic signaling increases newborn GCs survival, mimicking the effects of olfactory enrichment. These results, in conjunction with other studies on cholinergic or glutamatergic centrifugal afferents (Cooper-Kuhn et al., 2004; Oboti et al., 2011), suggest that the selection of newborn elements in this peripheral sen- sory circuitry depends on the concurrence of olfactory inputs and the consequent back- ward stimulation from downstream brain nuclei. This eventually results in neuronal activation and survival in those OB regions precisely and specifically matched with the activity patterns evoked by this concerted sensory stimulation. Moreno et al. give cre- dence to this hypothesis by showing that familiarized odorants induce higher activ- ity in newborn cells (% BrdU+/Zif268+) under enriched conditions, an effect that is abolished when the noradrenergic blocker is given during the olfactory enrichment pro- tocol. This suggests that centrifugal brain activity alone (in this case noradrenergic) represents an important factor in determin- ing the extent of OB neuronal excitability, an effect particularly evident in the new- born GCs. It would be interesting in the future to determine if the spatial mapping of BrdU/Zif268-positive cells match the activity pattern of familiarized odors or if it is more widespread. A detailed screening of NA-receptor expression in these cells along different maturational steps would certainly August 2012 | Volume 6 | Article 117 | 1