RT Journal Article SR Electronic T1 Action of the Noradrenergic System on Adult-Born Cells Is Required for Olfactory Learning in Mice JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 3748 OP 3758 DO 10.1523/JNEUROSCI.6335-11.2012 VO 32 IS 11 A1 Moreno, Melissa M. A1 Bath, Kevin A1 Kuczewski, Nicola A1 Sacquet, Joƫlle A1 Didier, Anne A1 Mandairon, Nathalie YR 2012 UL http://www.jneurosci.org/content/32/11/3748.abstract AB We have previously shown that an experience-driven improvement in olfactory discrimination (perceptual learning) requires the addition of newborn neurons in the olfactory bulb (OB). Despite this advance, the mechanisms which govern the selective survival of newborn OB neurons following learning remain largely unknown. We propose that activity of the noradrenergic system is a critical mediator providing a top-down signal to control the selective survival of newly born cells and support perceptual learning. In adult mice, we used pharmacological means to manipulate the noradrenergic system and neurogenesis and to assess their individual and additive effects on behavioral performance on a perceptual learning task. We then looked at the effects of these manipulations on regional survival of adult-born cells in the OB. Finally, using confocal imaging and electrophysiology, we investigated potential mechanisms by which noradrenaline could directly influence the survival of adult-born cells. Consistent with our hypotheses, direct manipulation of noradrenergic transmission significantly effect on adult-born cell survival and perceptual learning. Specifically, learning required both the presence of adult-born cell and noradrenaline. Finally, we provide a mechanistic link between these effects by showing that adult-born neurons receive noradrenergic projections and are responsive to noradrenaline. Based upon these data we argue that noradrenergic transmission is a key mechanism selecting adult-born neurons during learning and demonstrate that top-down neuromodulation acts on adult-born neuron survival to modulate learning performance.