The tremendous variety of odors perceived in the environment as well as aromas perceived in food result from the processing of complex chemical mixtures of volatile compounds that should be efficiently processed by the olfactory system. It is known for decades that this processing generates perceptual interactions, such as masking, synergy, or perceptual blending, which contribute to elaborating a synthetic brain representation of the complex chemical information. Nevertheless, the perceptual processes underlying these interactions are still poorly known. In the academic MultiMix research project, we set out a multidisciplinary approach to identify the characteristics of odorants and olfactory receptors (ORs) that could support perceptual interactions. We hypothesized that odorants involved in interactions at the peripheral level should share common structural characteristics to allow the activation of a common set of ORs. To test this hypothesis, we selected 4 model mixtures in which masking (octanal + citronellal [1], isoamyl acetate + whiskey lactone [2]) or blending (pineapple [3], red cordial mixtures [4]) has been reported. We first used the RNA-sequencing approach in mice [5,6] to identify the ORs responding to either single odorants or mixtures. In a second step, we checked if the identified ORs responded to the target odorants using an in vitro cellular assay [1], and if the expected perceptual interactions occurred in vivo through EOG recordings [2] on mice's olfactory mucosa, and sensory evaluation [2] in humans. Finally, we examined through an in silico approach [7,8] the common molecular features between the odorants involved in the mixtures. When combined, the results of this multidisciplinary approach highlighted that perceptual interactions such as masking could rise from competition between odorants at the OR level, but that other interactions such as perceptual blending most likely originate from more central integrative brain processing [9]. Références: 1. El Mountassir, F. et al. Flavour Fragrance J, 2016, 31(5), 400‑4072. Chaput, M. et al. Eur J Neurosci, 2012, 35(4), 584‑5973. Le Berre, E., et al. Chem. Senses, 2008. 33(4): p. 389-3954. Romagny, S. et al. Flavour Fragrance J, 2018, 33(1), 97‑1055. Jiang, Y., et al. Nat Neurosci, 2015. 18(10): p. 1446-54.6. Von der Weid, B., et al. Nat Neurosci, 2015. 18(10): p. 1455-637. Tromelin, A. et al. Molecules, 2020, 25(13), 30328. Rugard M. et al. Plos One, 2021, 16(5), e02524869. Thomas-Danguin, T., et al. Front. Psychol., 2014. 5