Laura CHALENCON defense thesis - Bases neurales de la valeur hédonique des odeurs et ses altérations au cours du vieillissement

Abstract

Sensory information elicits emotional responses that drive our approach or withdrawal behavior, reflecting the hedonic value of the sensory stimulus. The hedonic value is a dominant parameter of olfactory perception. Indeed, our first reaction to an odorant is generally "I like" or "I don't like" before even try to identify it.
It is well established that the hedonic value of an odorant has an innate component but it can also be modified by a large number of parameters including aging. The age-related alteration of odor hedonics can profoundly affect the quality of life by modifying social interactions or food intake. During my thesis, I investigated the neural mechanisms underlying the attraction induced by pleasant odorants and their alterations during aging.
In a previous study, our group showed that pleasant odorants are represented in the posterior part of the olfactory bulb, the first cortical relay of olfactory information. These data raised the question of how the hedonic information present in the olfactory bulb is processed by the rest of the brain to generate an attractive behavior. As motivated behaviors are known to rely on the reward system, in a first study, we have investigated the role of this neural circuit in the attraction induced by pleasant odorants. We first demonstrated that optogenetic activation of the posterior olfactory bulb induced an intracranial self-stimulation behavior, revealing the capacity of this region to recruit the reward system. This conditioning is accompanied by neural activation of the ventral tegmental area and the olfactory tubercle. This last structure is part of the ventral striatum, giving it the particularity of being at the crossroads between the olfactory system and the reward system. Using the iDISCO technic, we showed that the posterior olfactory bulb projects preferentially to the olfactory tubercle. Furthermore, we revealed that attractive odorants specifically activate the olfactory tubercle and induce a conditioned place preference under control of the dopaminergic transmission. We extended the evidence of a rewarding power of some odorants with a strong involvement of the olfactory tubercle to humans. Indeed, thanks to experiments conducted in living labs and fMRI, we showed that attractive odorants induced conditioned place preference and an increase of the BOLD signal specifically in the olfactory tubercle.
In a second study, I investigated the impact of aging on the perception of pleasant odorants and the neural bases underlying it. We showed that, in accordance with previous studies in humans, the pleasantness of some odorants is altered during aging in mice. We have
also shown that some odorants remained attractive and still activated the posterior olfactory bulb and the olfactory tubercle, whereas this neural pattern was no longer observed for odorants that have lost their attractive power. Moreover, we revealed that optogenetic activation of the posterior olfactory bulb in elderly mice is able to induce intracranial self-stimulation behavior. Finally, this conditioning was accompanied by neural activation of the olfactory tubercle, without activation of the ventral tegmental area, revealing only partial recruitment of the reward system.
In a third study, we proposed to use the motivational property of odorants to identify new behavioral parameters to assess odor hedonic value in humans. We recorded and automatically analyzed freely moving human subjects exploring odorized flasks and revealed that five motor parameters are linked to odor hedonics: the approach and withdrawal speeds of the odorant to the nose, the distance between the flask and the nose, the number of sniff and distance of withdrawal corresponding to the maximal distance between the nose and the flask after odor sniffing. We thus highlighted new, non-verbal and non-invasive parameters to evaluate olfactory hedonics in humans based on the assessment of odor motivated behavior.
Thus, during my thesis, I demonstrated the existence of a direct and privileged pathway between the olfactory system and the reward system conferring to some odorants a rewarding effect that could explain their strong attractive power. In addition, I showed that an alteration of this pathway could be at the origin of the selective olfactory anhedonia observed during aging.