ED Sciences de la Vie et de la Santé
Olfaction and feeding behaviour: Neuronal substrates underlying odour modulation of food intake regulating neuronal circuits
by Louise EYGRET (Nutrition et Neurobiologie Intégrée)
The defense will take place at 14h00 - Amphithéâtre BBS Bâtiment Biologie Santé 2 rue Docteur Hoffmann Martinot 33000 Bordeaux
in front of the jury composed of
- David JARRIAULT - Chargé de recherche - Université de Bordeaux - Directeur de these
- Sophie STECULORUM - Directrice de recherche - Max Planck Institute for Metabolism Research - Rapporteur
- Pablo CHAMERO - Directeur de recherche - Université de Tours - Rapporteur
- Claire MARTIN - Directrice de recherche - Université Paris Cité - Examinateur
Maintaining a stable body weight is a major challenge in modern societies, and current treatments have limited efficacy and numerous side effects. Olfaction emerges as a promising candidate to modulate food intake in a more physiological way. Food odours are ubiquitous environmental cues that can influence meal initiation, meal size, and metabolic responses. While the role of hypothalamic agouti-related peptide (AgRP) and proopiomelanocortin (POMC) neurons in the central control of feeding is well established, the contribution of sensory cues to this regulation remains poorly understood. This thesis investigates how food odours with innate or learned valence modulate food intake and hypothalamic appetite-regulating circuits, focusing on AgRP and POMC neurons. Using an olfactory exploration assay, we identified several food odours as attractive and appetitive. Bacon and butter odours induce innate attraction associated with an increase in food consumption, whereas peanut butter odour becomes appetitive only after odour-nutrient association, reflecting a learned valence. These findings highlight the ability of specific food odours to drive feeding and approach behaviour. After exposure to an obesogenic diet rich in sugars and fats, the orexigenic effect is abolished. To link these effects to hypothalamic circuits, we recorded in vivo AgRP and POMC neuronal activity using fibre photometry, synchronising neuronal signal with odour-evoked sniffing monitored by plethysmography. All tested odours rapidly inhibit AgRP and POMC neurons, consistent with an anticipation of feeding. These data show that food odour detection modulates the activity of the melanocortin network. We next examined ex vivo the electrophysiological properties of these neurons following prolonged odorant exposure. Bacon odour enhances excitatory drive onto POMC and AgRP neurons while specifically reducing POMC firing frequency. Other odours produce weaker effects, modulating the intrinsic excitability of neurons without affecting their firing rate. Each odour elicits distinct changes in electrophysiological parameters within the arcuate nucleus. Prolonged odour exposure differentially shapes neuronal dynamics compared with brief acute stimulation. Finally, we investigated the anatomical links between the olfactory system and the hypothalamus, focusing on the medial amygdala, previously proposed as a relay between those two systems. Its viral inhibition abolishes the orexigenic effect of bacon odour without altering its attractiveness, whereas naïve and learned responses to the peanut butter odour remain unchanged. The medial amygdala thus appears to act as a key relay for the orexigenic component of innate but not learned olfactory cues. To conclude, this thesis demonstrates the orexigenic power of food odours with innate or learned valence, and shows that they finely tune the activity of melanocortin neurons in the arcuate nucleus, contributing to anticipatory mechanisms of food consumption. The medial amygdala is identified as a core relay linking innate olfactory signals to food intake. Altogether, this work advances the understanding of sensory regulation of food intake and opens perspectives for safer, non-pharmacological strategies to help regulate appetite.