Oboti and Platel Figure 1 | Principal brain centrifugal afferents to the olfactory bulb. The modulatory role of noradrenergic, glutamatergic, and cholinergic brain afferents on neuronal survival in the olfactory bulb (main and accessory, mOB/aOB) has been reported by the studies indicated by the references. The projection sites of noradrenergic (locus coeruleus, LC), glutamatergic (medial, cortical amygdala, and anterior olfactory nucleus; MeA, ACo, AON), and cholinergic afferents (cholinergic basal forebrain, CBF) to the olfactory bulb are represented unilaterally in the brain model and in the coronal planes on the right, ipsilaterally to the targeted bulbar region (mOB/aOB). Other abbreviations used: svz-rms, sub-ventricular zone-rostral migratory stream; GrL, granular layer; lv, lateral ventricle; 4v, fourth ventricle. sustain this interpretation and give a more precise view of their functional integration dynamics. However, limited by the experi- mental paradigm adopted in this work, OB neurogenesis and noradrenergic signaling seem to be tightly connected. Accordingly, ablation of younger neurons through short- term AraC treatment impedes olfactory enrichment to improve mice discriminatory abilities. In contrast to what happens when new neurons are still present, this defect is not rescued by the stimulation of the noradrenergic system. Eventually lesion- ing of the noradrenergic inputs on the OB, possibly the LC, would further confirm this observation. These results strongly suggest that olfactory perceptual learning in mice is improved specifically by the noradrenergic control of newborn cell functional integra- tion. This direct link is further supported by the observation of synaptic contacts between young GCs and noradrenergic fib- ers and direct GCs response to noradrena- line stimulation. These interesting results, combined with other studies, support the idea that the selection of functional elements in the peripheral sensory circuitry depends on the concurrence of external inputs and the con- sequent backward stimulation from down- stream brain nuclei (Gilbert and Sigman, 2007; Fletcher and Chen, 2010; Robinson et al., 2011). This opens the way to new connectome studies focused on the role of Frontiers in Neuroscience | Neurogenesis other regions sending afferent projections to the OB, such as the anterior olfactory nucleus, the limbic system, the piriform cortex, among others. The main question should now shift from why individual cells are important, to how the whole brain uses them. Indeed, either stimulus novelty, arousal, or the rewarding value of olfactory cues, seem to define the functional context in which olfactory bulb neurogenesis is modulated (Figure 1). 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Neurosci. 6:117. doi: 10.3389/fnins.2012.00117 This article was submitted to Frontiers in Neurogenesis, a specialty of Frontiers in Neuroscience. Copyright © 2012 Oboti and Platel. This is an open- access article distributed under the terms of the Creative Commons Attribution License, which permits use, dis- tribution and reproduction in other forums, provided the original authors and source are credited and sub- ject to any copyright notices concerning any third-party graphics etc. August 2012 | Volume 6 | Article 117 | 2