Primary olfactory determinants, that is, the entities that actually bind to the different classes of olfactory receptor neurons, are generally thought to be different atomic aspects, or specific combinations of those aspects, of the effective molecules. In rare cases, such as with some insect pheromones, the entire molecule can act as the olfactory determinant. The current best interpretation of sensory data from many different model animals suggests that numerous different classes of olfactory receptor neuron can be found on any type of olfactory organ (nose) and that the receptors on each different class of neuron are keyed to a single kind of olfactory determinant.

The path from odorant to perception is quite complex. The initial events in olfaction take place in an olfactory neuroepithelium situated in the posterior nasal cavity. Olfaction begins with sniffing, that transports odorant molecules into the nose and delivers them to the mucus layer covering the olfactory epithelium. The binding of the odorant by a receptor protein initiates an intracellular cascade of signal transduction events, including the G-protein-dependent production of second messenger molecules, leading to opening of ion channels and passing of ion currents. This process triggers an action potential in the olfactory receptor neurons (ORNs) that projects directly to the olfactory bulb (OB). The signal is then transmitted to the anterior olfactory nucleus, piriform cortex, periamygdaloid cortex, and entorhinal cortex via olfactory stria. The signal at piriform cortex and periamygdaloid cortex is then sent to the thalamus and frontal cortex, where it is recognized and interpreted. The signal received at the entorhinal cortex projects to the hippocampus, where recognition memory of odors is processed. The anterior olfactory nucleus is involved in the processing of olfactory features and construction of representations (gestalts) for odorants. The correlations between olfactory gestalts are processed by the piriform cortex in association with frontal, entorhinal, and periamygdaloid areas. The periamygdaloid area is involved in processing the emotional information of the olfactory stimuli and memory encoding, whereas the entorhinal cortex collects and distributes information about olfactory memory and serves as a top-down modulator of olfactory cortical function. The medial and orbital parts of the frontal cortex are involved in cognitive integration of all sensory stimuli in relation to prior experiences. The thalamus’ role in olfaction is still controversial, whereas its involvement in odor thresholding and patterns of sniffing has been verified, at least in humans.

The fundamental mechanism of olfaction, is not fully understood. Presently, the most accepted theories of olfaction are either based on molecular shape (1, 2) or on vibrational properties of molecules (3-5). The first approach, a so-called lock-and-key mechanism, assumes the shape of the molecule determines the characteristic odor. The other suggested that molecular vibrations are the basis for odor specificity in different molecules. In 2011 Franco et al. (6) demonstrated that fruit flies (Drosophila melanogaster) can differentiate between regular odorants and their deuterated isotopes. Two years later Gane et al. (7) reported that also humans are capable of discriminating musk molecules from their deuterated isotopes. As deuteration does not change the shape of a molecule, the lock-and-key model is insufficient to explain those findings. The shape and vibrational models are highly debated and require new experimental and theoretical data (8, 9).

1.            Amoore JE. Stereochemical theory of olfaction. Nature. 1963;198:271-2. Epub 1963/04/20. PubMed PMID: 14012641.

2.            Moncrieff RW. The characterization of odours. J Physiol. 1954;125:453-65.

3.            Dyson GM. The Scientific basis of odour. Chem  Ind. 1938;57:647-51.

4.            Turin L. A spectroscopic mechanism for primary olfactory reception. Chem Senses. 1996;21(6):773-91. PubMed PMID: AN 1997:66428.

5.            Wright RH. Odor and molecular vibration: Neural coding of olfactory information. J Theor Biol. 1977;64(3):473-502.

6.            Franco MI, Turin L, Mershin A, Skoulakis EMC. Molecular vibration-sensing component in Drosophila melanogaster olfaction. Proc Nat Acad Sci. 2011. doi: 10.1073/pnas.1012293108.

7.            Gane S, Georganakis D, Maniati K, Vamvakias M, Ragoussis N, Skoulakis EM, Turin L. Molecular vibration-sensing component in human olfaction. PLoS One. 2013;8(1):e55780. Epub 2013/02/02. doi: 10.1371/journal.pone.0055780. PubMed PMID: 23372854; PMCID: 3555824.

8.            Block E, Jang S, Matsunami H, Sekharan S, Dethier B, Ertem MZ, Gundala S, Pan Y, Li S, Li Z, Lodge SN, Ozbil M, Jiang H, Penalba SF, Batista VS, Zhuang H. Implausibility of the vibrational theory of olfaction. Proc Natl Acad Sci U S A. 2015;112(21):E2766-74. Epub 2015/04/23. doi: 10.1073/pnas.1503054112. PubMed PMID: 25901328; PMCID: Pmc4450420.

9.            Turin L, Gane S, Georganakis D, Maniati K, Skoulakis EMC. Plausibility of the vibrational theory of olfaction. Proc Nat Acad Sci 2015;112(25):E3154. doi: 10.1073/pnas.1508035112.

I do not have much experience and research in this aspect, but from practical observation, I feel: memory and age have a huge impact on olfaction. And we all know very well these are neurological entities so to the best Neural factor, especially memory cell play important role in determining primaries of olfaction.