Olfactory perceptual learning requires adult neurogenesis

Abstract

Perceptual learning is required for olfactory function to adapt appropriately to changing odor environments. We here show that newborn neurons in the olfactory bulb are not only involved in, but necessary for, olfactory perceptual learning. First, the discrimination of perceptually similar odorants improves in mice after repeated exposure to the odorants. Second, this improved discrimination is accompanied by an elevated survival rate of newborn inhibitory neurons, preferentially involved in processing of the learned odor, within the olfactory bulb. Finally, blocking neurogenesis before and during the odorant exposure period prevents this learned improvement in discrimination. Olfactory perceptual learning is thus mediated by the reinforcement of functional inhibition in the olfactory bulb by adult neurogenesis. discrimination ͉ mice ͉ enrichment ͉ olfactory bulb P erceptual learning is an implicit (nonassociative) form of learning in which discrimination between sensory stimuli is improved by previous experience (1). For instance, animals trained on a tactile discrimination task improve their behavioral performances and in parallel, the neural representation of the stimuli is sharpened (2, 3). In the olfactory modality, perceptual learning has been shown to occur in humans (4), and an experimental model of olfactory perceptual learning has recently been proposed in rats (5). Olfactory perceptual learning is crucial for basic olfactory functions because it sets the degree of discrimination between stimuli, and thus contributes to the perceptual representation of the environment, which guides the animal's behavior. However, neural mechanisms underlying such changes of perception remain elusive. We here show that a modulation of newborn cell survival in the olfactory bulb (OB) underlies olfactory perceptual learning. We show that neurogenesis is not only involved in, but necessary for perceptual learning to occur.We have shown that odor enrichment enhances rats' ability to discriminate between chemically similar odorants in a relatively odor-unspecific manner (5, 6). Indeed, the discrimination of a pair of similar odorants is improved by enrichment with the same odorants or with other odorants that activate regions of the OB partially overlapping with the regions activated by the discriminated pair. Even if the mechanisms underlying this learning remain unclear, it has been shown that infusions of NMDA into the OB improves odor discrimination in a manner similar to odor enrichment indicating that changes in OB processing contribute at least partially to the perceptual plasticity (5). A computational model proposed that activation of OB neurons produces widespread changes in inhibitory processing, which can underlie the observed improvement of odor discrimination (5). In support to this model, odor exposure has been shown to increase inhibition of mitral cells (7) and to increase the responsiveness of the inhibitory granule cells to odorants, as measured by expression of an immediate early gene (8).Inhibitory neuro...

Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons

“…Sensory experience might promote cell survival during a specific critical window, when new neurons receive synaptic inputs from preexisting circuits (6-9) and exhibit long-term potentiation (LTP) (10). During this window, an odor-reward association task (but not a mere odor exposure) promotes cell survival (11,12) and specific activation of adult-born neurons monitored through immediate early gene labeling (13,14). As a result, olfactory memory is impaired when adult neurogenesis is compromised (13,15).…”

What happens to olfaction without adult neurogenesis?

“…The work of Breton-Provencher et al, together with recently published analyses of animals with impaired adult neurogenesis provides us with precious food for thought concerning the possible role of new neurons (Imayoshi et al, 2008;Clelland et al, 2009;Deng et al, 2009;Kitamura et al, 2009;Lazarini et al, 2009;Moreno et al, 2009;Valley et al, 2009). The contrasting results obtained in different studies blocking adult neurogenesis and assessing olfactory behavior highlight the need for further investigations to decipher the precise function of adult neurogenesis for the sense of smell.…”

“…Overall, these independent studies seem to show, consistently, that blocking adult neurogenesis in the OB does not affect spontaneous discrimination between different odors (Imayoshi et al, 2008;Breton-Provencher et al, 2009;Lazarini et al, 2009). However, another recent study showed that blocking adult neurogenesis resulted in a dramatic decrease in performance in a task involving discrimination between two perceptually similar odorants after passive exposure (Moreno et al, 2009). Unlike BretonProvencher et al, Lazarini et al reported that the blockade of adult neurogenesis had no effect on odor detection thresholds.…”

“…Four other independent research groups have also recently studied the effect of blocking adult neurogenesis on olfactory behavior (Imayoshi et al, 2008;Lazarini et al, 2009;Moreno et al, 2009;Valley et al, 2009). However, no clear consensus emerges from their results.…”

“…In particular, they reported that AraC-treated mice performed well in exercises involving spontaneous locomotor activity, object exploration and recognition. They also tested the treated mice in tail suspension and novelty suppressed feeding 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.…”