Age-related differences in perception and coding of attractive odorants in mice.

Hedonic perception deeply changes with aging, significantly impacting health and quality of life in elderly. In young adult mice, an odor hedonic signature is represented along the antero-posterior axis of olfactory bulb, and transferred to the olfactory tubercle and ventral tegmental area, promoting approach behavior. Here, we show that while the perception of unattractive odorants was unchanged in older mice (22 months), the appreciation of some but not all attractive odorants declined. Neural activity in the olfactory bulb and tubercle of older mice was consistently altered when attraction to pleasant odorants was impaired while maintained when the odorants kept their attractivity. Finally, in a self-stimulation paradigm, optogenetic stimulation of the olfactory bulb remained rewarding in older mice even without ventral tegmental area's response to the stimulation. Aging degrades behavioral and neural responses to some pleasant odorants but rewarding properties of olfactory bulb stimulation persisted, providing new insights into developing novel olfactory training strategies to elicit motivation even when the dopaminergic system is altered as observed in normal and/or neurodegenerative aging.

A stress-sensitive frontostriatal circuit supporting effortful reward-seeking behavior.

Effort valuation-a process for selecting actions based on the anticipated value of rewarding outcomes and expectations about the work required to obtain them-plays a fundamental role in decision-making. Effort valuation is disrupted in chronic stress states and is supported by the anterior cingulate cortex (ACC), but the circuit-level mechanisms by which the ACC regulates effort-based decision-making are unclear. Here, we show that ACC neurons projecting to the nucleus accumbens (ACC-NAc) play a critical role in effort valuation behavior in mice. Activity in ACC-NAc cells integrates both reward- and effort-related information, encoding a reward-related signal that scales with effort requirements and is necessary for supporting future effortful decisions. Chronic corticosterone exposure reduces motivation, suppresses effortful reward-seeking, and disrupts ACC-NAc signals. Together, our results delineate a stress-sensitive ACC-NAc circuit that supports effortful reward-seeking behavior by integrating reward and effort signals and reinforcing effort allocation in the service of maximizing reward.

Chronic unpredictable mild stress alters odor hedonics and adult olfactory neurogenesis in mice.

Experiencing chronic stress significantly increases the risk for depression. Depression is a complex disorder with varied symptoms across patients. However, feeling of sadness and decreased motivation, and diminished feeling of pleasure (anhedonia) appear to be core to most depressive pathology. Odorants are potent signals that serve a critical role in social interactions, avoiding danger, and consummatory behaviors. Diminished quality of olfactory function is associated with negative effects on quality of life leading to and aggravating the symptoms of depression. Odor hedonic value (I like or I dislike this smell) is a dominant feature of olfaction and guides approach or avoidance behavior of the odor source. The neural representation of the hedonic value of odorants is carried by the granule cells in the olfactory bulb, which functions to modulate the cortical relay of olfactory information. The granule cells of the olfactory bulb and those of the dentate gyrus are the two major populations of cells in the adult brain with continued neurogenesis into adulthood. In hippocampus, decreased neurogenesis has been linked to development or maintenance of depression symptoms. Here, we hypothesize that chronic mild stress can alter olfactory hedonics through effects on the olfactory bulb neurogenesis, contributing to the broader anhedonia phenotype in stress-associated depression. To test this, mice were subjected to chronic unpredictable mild stress and then tested on measures of depressive-like behaviors, odor hedonics, and measures of olfactory neurogenesis. Chronic unpredictable mild stress led to a selective effect on odor hedonics, diminishing attraction to pleasant but not unpleasant odorants, an effect that was accompanied by a specific decrease in adult neurogenesis and of the percentage of adult-born cells responding to pleasant odorants in the olfactory bulb.

Identification of new behavioral parameters to assess odorant hedonic value in humans: A naturalistic approach.

BACKGROUND: When you smell an odorant, your first reaction will certainly be either I like it or I dislike it. This primary reaction is a reflection of what is called the "hedonic value" of the odor. Very often, this hedonic value dominates the olfactory percept, more than olfactory identification or intensity. This component of olfactory perception is of primary importance for guiding behavior: avoiding danger (the smell of smoke, gas, etc.), consuming food, or seduction. Olfactory hedonics can be assessed using a large number of methods in humans, including psychophysical measures, autonomic responses, measurement of facial expressions or peripheral nervous activity. All of these techniques have their limitations: subjectivity, invasiveness, need for expertise, etc. A NEW METHOD: The olfactory system is closely linked to the reward system, the role of which is to mediate motivated behavior. In this context, we propose that the capacity odorants have of recruiting the reward system and thus inducing motivated behavior can be used to identify new behavioral parameters to assess odor hedonic value in humans. RESULTS: We recorded freely moving human participants exploring odors emanating from flasks, and showed that five parameters linked to motivated behavior were closely linked to odor hedonics: speed of approach to the nose and withdrawal of the flask containing the odorant, distance between flask and nose, number of samplings, and withdrawal distance (maximal distance between nose and flask after odor sampling). CONCLUSIONS: We highlighted new non-verbal and non-invasive parameters to evaluate olfactory hedonics in humans based on the assessment of odor-motivated behavior.

Neural processing of the reward value of pleasant odorants.

Pleasant odorants are represented in the posterior olfactory bulb (pOB) in mice. How does this hedonic information generate odor-motivated behaviors? Using optogenetics, we report here that stimulating the representation of pleasant odorants in a sensory structure, the pOB, can be rewarding, self-motivating, and is accompanied by ventral tegmental area activation. To explore the underlying neural circuitry downstream of the olfactory bulb (OB), we use 3D high-resolution imaging and optogenetics and determine that the pOB preferentially projects to the olfactory tubercle, whose increased activity is related to odorant attraction. We further show that attractive odorants act as reinforcers in dopamine-dependent place preference learning. Finally, we extend those findings to humans, who exhibit place preference learning and an increase BOLD signal in the olfactory tubercle in response to attractive odorants. Thus, strong and persistent attraction induced by some odorants is due to a direct gateway from the pOB to the reward system.

Odor hedonics coding in the vertebrate olfactory bulb.

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.

Role of Adult-Born Versus Preexisting Neurons Born at P0 in Olfactory Perception in a Complex Olfactory Environment in Mice.

Olfactory perceptual learning is defined as an improvement in the discrimination of perceptually close odorants after passive exposure to these odorants. In mice, simple olfactory perceptual learning involving the discrimination of two odorants depends on an increased number of adult-born neurons in the olfactory bulb, which refines the bulbar output. However, the olfactory environment is complex, raising the question of the adjustment of the bulbar network to multiple discrimination challenges. Perceptual learning of 1 to 6 pairs of similar odorants led to discrimination of all learned odor pairs. Increasing complexity did not increase adult-born neuron survival but enhanced the number of adult-born neurons responding to learned odorants and their spine density. Moreover, only complex learning induced morphological changes in neurons of the granule cell layer born during the first day of life (P0). Selective optogenetic inactivation of either population confirmed functional involvement of adult-born neurons regardless of the enrichment complexity, while preexisting neurons were required for complex discrimination only.

Short-term availability of adult-born neurons for memory encoding.

Adult olfactory neurogenesis provides waves of new neurons involved in memory encoding. However, how the olfactory bulb deals with neuronal renewal to ensure the persistence of pertinent memories and the flexibility to integrate new events remains unanswered. To address this issue, mice performed two successive olfactory discrimination learning tasks with varying times between tasks. We show that with a short time between tasks, adult-born neurons supporting the first learning task appear to be highly sensitive to interference. Furthermore, targeting these neurons using selective light-induced inhibition altered memory of this first task without affecting that of the second, suggesting that neurons in their critical period of integration may only support one memory trace. A longer period between the two tasks allowed for an increased resilience to interference. Hence, newly formed adult-born neurons regulate the transience or persistence of a memory as a function of information relevance and retrograde interference.

Non-imaged based method for matching brains in a common anatomical space for cellular imagery.

BACKGROUND: Cellular imagery using histology sections is one of the most common techniques used in Neuroscience. However, this inescapable technique has severe limitations due to the need to delineate regions of interest on each brain, which is time consuming and variable across experimenters. NEW METHOD: We developed algorithms based on a vectors field elastic registration allowing fast, automatic realignment of experimental brain sections and associated labeling in a brain atlas with high accuracy and in a streamlined way. Thereby, brain areas of interest can be finely identified without outlining them and different experimental groups can be easily analyzed using conventional tools. This method directly readjusts labeling in the brain atlas without any intermediate manipulation of images. RESULTS: We mapped the expression of cFos, in the mouse brain (C57Bl/6J) after olfactory stimulation or a non-stimulated control condition and found an increased density of cFos-positive cells in the primary olfactory cortex but not in non-olfactory areas of the odor-stimulated animals compared to the controls. COMPARISON WITH EXISTING METHOD(S): Existing methods of matching are based on image registration which often requires expensive material (two-photon tomography mapping or imaging with iDISCO) or are less accurate since they are based on mutual information contained in the images. Our new method is non-imaged based and relies only on the positions of detected labeling and the external contours of sections. CONCLUSIONS: We thus provide a new method that permits automated matching of histology sections of experimental brains with a brain reference atlas.