Consolidation of an Olfactory Memory Trace in the Olfactory Bulb Is Required for Learning-Induced Survival of Adult-Born Neurons and Long-Term Memory

Background: It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. Methodology/Principal Findings: Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days), but not a massed (within day), learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. Conclusion/Significance: We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival durin

Neural basis of olfactory preferences

La valence hédonique des odeurs (leur caractère plus ou moins plaisant) est une dimension primordiale de l'olfaction chez l'homme. Les préférences olfactives sont fortement façonnées par l'expérience, la culture et le contexte. Cependant, des études récentes montrent qu'elles seraient également partiellement dictées par les propriétés physicochimiques des molécules odorantes. L'objectif de ce travail est d'une part de préciser les paramètres physico-chimiques des odorants déterminant la dimension hédonique de la perception. D'autre part, nous avons recherché comment le premier relais cortical olfactif, le bulbe olfactif (BO) encode la valence hédonique des odeurs, qu'elle soit spontanée ou modulée par l apprentissage. Dans une première partie, nous avons exploré l'effet de la complexité des odorants sur la perception olfactive chez l'homme. Nous avons montré que ce paramètre influence à la fois la complexité perceptuelle (le nombre de notes olfactives évoquées) et la valence hédonique des odeurs. Ceci suggère que le système olfactif est capable de coder la valeur hédonique à partir de la molécule odorante chez l'homme. Dans une seconde partie, nous avons mis à profit la conservation de l'organisation anatomofonctionnelle du système olfactif chez les mammifères pour explorer, dans le modèle murin, la représentation de la valence hédonique des odeurs dans le BO. Nous avons analysé la réponse bulbaire à des odorants non biologiques plus ou moins complexes, et donc attractifs, grâce à la cartographie de l'expression des gènes précoces Zif268 et cFos. Nous mettons en évidence une activation postérieure du BO plus importante pour les odeurs les moins attractives. Dans une dernière partie, nous avons examiné la plasticité des représentations bulbaires quand la valence hédonique de l'odorant change. La valence des odorants a été modifiée chez la souris par apprentissage associatif appétitif ou aversif. La réponse bulbaire a ensuite été examinée en fonction de la valence acquise des odeurs. Nous montrons que lorsqu'un même odorant passe d'une valence positive à une valence négative, l'activité des interneurones granulaires diminue dans la partie postérieure du BO. Ceci indique un rôle de la distribution antéro-postérieure de l'activité bulbaire dans le codage de la valence hédonique apprise des odeurs. En raison du renouvellement constant des interneurones bulbaires à l'âge adulte, impliqués dans la mémoire associative olfactive, l effet de la modulation de la valence des odeurs sur la neurogenèse a également été déterminé. De façon intéressante, la neurogenèse adulte est impliquée dans ce processus car l'activité des cellules granulaires nouvellement formées diminue également dans le BO postérieur en réponse à l'odeur devenue aversive. Ainsi, les deux dernières parties suggèrent une plasticité de la représentation de la valeur hédonique sur l'axe antéro-postérieur selon que la préférence est spontanée ou acquise. Dans leur ensemble, ces trois études montrent d'une part que la complexité moléculaire des odorants est un facteur déterminant de la valence hédonique de l'odeur chez l'homme et la souris. D'autre part, elles démontrent l'existence d'une trace neurale de la valence spontanée ou apprise des odeurs, exprimée le long de l'axe antéro-postérieur du BO, révélant une nouvelle régionalisation fonctionnelle du BOThe first dimension of human olfactory perception is the pleasantness of smells. Numerous studies suggest that olfactory preferences are strongly modulated by experience, culture and context. However, recent evidences suggest that olfactory hedonics could be also partly driven by the physico-chemical features of the odorant molecule. The objective of this work was first to identify the odorant’s physico-chemical parameters determining odor hedonic valence. Second, we studied how the first olfactory cerebral relay, the olfactory bulb (OB), encodes spontaneous or learned odor hedonic valence. In a first part, we looked at the effect of the structural complexity of odorant molecules on human olfactory perception and found that this parameter can influence both the odorant’s perceptual complexity (number of olfactory notes evoked) and its hedonic valence. This suggests that the human olfactory system is able to encode odorant hedonic valence from the molecule itself. In a second part, taking advantage of the highly conserved olfactory system in mammals and the shared olfactory preferences between mice and human, we analyzed the OB response to attractive (complex) or less attractive (less complex) odorants by mapping the expression of the immediate early genes Zif268 and cFos. Results indicated a stronger activity in the posterior OB for the low compared to the high attractiveness odors. In a last part, we examined the plasticity of the odorant bulbar representation when the predictive value of the odorant changes. We first modulated the valence of an odorant using an appetitive or an aversive learning in mice and measured the OB response to this odorant depending on its acquired positive or negative valence. We found that, when the same odorant goes from positive to negative valence, the responsiveness of granule interneurons in the posterior part of the OB was dramatically decreased. This indicated that the anteroposterior distribution of activation conveys information regarding the acquired valence of the odorants. Because the OB undergoes a constant neuronal turnover during adulthood, which has been implicated in associative memory, we also looked at the effect of valence modulation on neurogenesis. Interestingly, neurogenesis was involved in this process since the activity of newborn granule cells present in the posterior OB was also decreased in response to the negatively-reinforced odorant. Interestingly, the two last parts of this work suggest a plasticity of the neural representation of hedonic value along the antero-posterior axis depending on the spontaneous versus acquired preference. Altogether, these results show first that molecular complexity is an important factor determining odor hedonic valence in humans and mice. Second, they show an early neural trace of spontaneous and learned hedonic valence which is expressed along the anteroposterior axis of the OB. The latter data reveal an early coding of hedonics in the OB and a yet unknown antero-posterior functional regionalization of the O

Chronic unpredictable stress induces anxiety-like behaviors in young zebrafish

Exposure to stress during early life affects subsequent behaviors and increases the vulnerability to adult pathologies, a phenomenon that has been well documented in humans and rodents. In this study, we introduce a chronic unpredictable stress protocol adapted to young zebrafish, which is an increasingly popular vertebrate model in neuroscience research. We exposed zebrafish to a series of intermittent and unpredictable mild stressors from day 10 to 17 post-fertilization. The stressed fish showed a reduced exploration of a novel environment one day post-stress and an increased responsiveness to dark-light transition two days post-stress, indicative of heightened anxiety-related behaviors. The stress-induced decrease in exploration lasted for at least three days and returned to control levels within one week. Moreover, stressed fish were on average 8% smaller than their control siblings two days post-stress and returned to control levels within one week. All together, our results demonstrate that young zebrafish exposed to chronic unpredictable stress develop growth and behavioral alterations akin to those observed in rodent models

Odor hedonics coding in the vertebrate olfactory bulb

International audienceAbstract Whether an odorant is perceived as pleasant or unpleasant (hedonic value) governs a range of crucial behaviors: foraging, escaping danger, and social interaction. Despite its importance in olfactory perception, little is known regarding how odor hedonics is represented and encoded in the brain. Here, we review recent findings describing how odorant hedonic value is represented in the first olfaction processing center, the olfactory bulb. We discuss how olfactory bulb circuits might contribute to the coding of innate and learned odorant hedonics in addition to the odorant’s physicochemical properties

Interhemispheric connections between olfactory bulbs improve odor detection.

Interhemispheric connections enable interaction and integration of sensory information in bilaterian nervous systems and are thought to optimize sensory computations. However, the cellular and spatial organization of interhemispheric networks and the computational properties they mediate in vertebrates are still poorly understood. Thus, it remains unclear to what extent the connectivity between left and right brain hemispheres participates in sensory processing. Here, we show that the zebrafish olfactory bulbs (OBs) receive direct interhemispheric projections from their contralateral counterparts in addition to top-down inputs from the contralateral zebrafish homolog of olfactory cortex. The direct interhemispheric projections between the OBs reach peripheral layers of the contralateral OB and retain a precise topographic organization, which directly connects similarly tuned olfactory glomeruli across hemispheres. In contrast, interhemispheric top-down inputs consist of diffuse projections that broadly innervate the inhibitory granule cell layer. Jointly, these interhemispheric connections elicit a balance of topographically organized excitation and nontopographic inhibition on the contralateral OB and modulate odor responses. We show that the interhemispheric connections in the olfactory system enable the modulation of odor response and contribute to a small but significant improvement in the detection of a reproductive pheromone when presented together with complex olfactory cues by potentiating the response of the pheromone selective neurons. Taken together, our data show a previously unknown function for an interhemispheric connection between chemosensory maps of the olfactory system

Interhemispheric connections between olfactory bulbs improve odor detection

Interhemispheric connections enable interaction and integration of sensory information in bilaterian nervous systems and are thought to optimize sensory computations. However, the cellular and spatial organization of interhemispheric networks and the computational properties they mediate in vertebrates are still poorly understood. Thus, it remains unclear to what extent the connectivity between left and right brain hemispheres participates in sensory processing. Here, we show that the zebrafish olfactory bulbs (OBs) receive direct interhemispheric projections from their contralateral counterparts in addition to top-down inputs from the contralateral zebrafish homolog of olfactory cortex. The direct interhemispheric projections between the OBs reach peripheral layers of the contralateral OB and retain a precise topographic organization, which directly connects similarly tuned olfactory glomeruli across hemispheres. In contrast, interhemispheric top-down inputs consist of diffuse projections that broadly innervate the inhibitory granule cell layer. Jointly, these interhemispheric connections elicit a balance of topographically organized excitation and nontopographic inhibition on the contralateral OB and modulate odor responses. We show that the interhemispheric connections in the olfactory system enable the modulation of odor response and contribute to a small but significant improvement in the detection of a reproductive pheromone when presented together with complex olfactory cues by potentiating the response of the pheromone selective neurons. Taken together, our data show a previously unknown function for an interhemispheric connection between chemosensory maps of the olfactory system

Olfactory perceptual learning requires action of noradrenaline in the olfactory bulb: comparison with olfactory associative learning

International audienceNoradrenaline contributes to olfactory-guided behaviors but its role in olfactory learning during adulthood is poorly documented. We investigated its implication in olfactory associative and perceptual learning using local infusion of mixed a1-b adrenergic receptor antagonist (labetalol) in the adult mouse olfactory bulb. We reported that associative learning, as opposed to perceptual learning, was not affected by labetalol infusions in the olfactory bulb. Accordingly, this treatment during associative learning did not affect the survival of bulbar adult-born neurons. Altogether, our results suggest that the noradrenergic system plays different parts in specific olfactory learning tasks and their neurogenic correlates

Context-driven activation of odor representations in the absence of olfactory stimuli in the olfactory bulb and piriform cortex

Sensory neural activity is highly context dependent and shaped by experience and expectation. In the olfactory bulb (OB), the first cerebral relay of olfactory processing, responses to odorants are shaped by previous experiences including contextual information thanks to strong feedback connections. In the present experiment, mice were conditioned to associate an odorant with a visual context and were then exposed to the visual context alone. We found that the visual context alone elicited exploration of the odor port similar to that elicited by the stimulus when it was initially presented. In the OB, the visual context alone elicited a neural activation pattern, assessed by mapping the expression of the immediate early gene zif268 (egr-1) that was highly similar to that evoked by the conditioned odorant, but not other odorants. This OB activation was processed by olfactory network as it was transmitted to the piriform cortex. Interestingly, a novel context abolished neural and behavioral responses. In addition, the neural representation in response to the context was dependent on top-down inputs, suggesting that context-dependent representation is initiated in cortex. Modeling of the experimental data suggests that odor representations are stored in cortical networks, reactivated by the context and activate bulbar representations. Activation of the OB and the associated behavioral response in the absence of physical stimulus showed that mice are capable of internal representations of sensory stimuli. The similarity of activation patterns induced by imaged and the corresponding physical stimulus, triggered only by the relevant context provides evidence for an odor-specific internal representation

Stimulus-specific behavioral responses of zebrafish to a large range of odors exhibit individual variability

Background Odor-driven behaviors such as feeding, mating, and predator avoidance are crucial for animal survival. The neural pathways processing these behaviors have been well characterized in a number of species, and involve the activity of diverse brain regions following stimulation of the olfactory bulb by specific odors. However, while the zebrafish olfactory circuitry is well understood, a comprehensive characterization linking odor-driven behaviors to specific odors is needed to better relate olfactory computations to animal responses. Results Here, we used a medium-throughput setup to measure the swimming trajectories of 10 zebrafish in response to 17 ecologically relevant odors. By selecting appropriate locomotor metrics, we constructed ethograms systematically describing odor-induced changes in the swimming trajectory. We found that adult zebrafish reacted to most odorants using different behavioral programs and that a combination of a few relevant behavioral metrics enabled us to capture most of the variance in these innate odor responses. We observed that individual components of natural food and alarm odors do not elicit the full behavioral response. Finally, we show that zebrafish blood elicits prominent defensive behaviors similar to those evoked by skin extract and activates spatially overlapping olfactory bulb domains. Conclusion Altogether, our results highlight a prominent intra- and inter-individual variability in zebrafish odor-driven behaviors and identify a small set of waterborne odors that elicit robust responses. Our behavioral setup and our results will be useful resources for future studies interested in characterizing innate olfactory behaviors in aquatic animals