How is the sense of smell generated?
Introduction
Can you envisage living without your nose? While there are lots of finding regarding how the eyes and ears function, we may ignore our sense of smell, which indeed contribute 70-75% of what perceive as taste from food. After all, we do actively “watch” TV, “listen” to music, but a lot of us seldom actively “smell” things in our daily life. The nose is small, but the generation of sense of smell is too complex to be fully understood still.
Main body
There are a myriad of differentiated cells responsible for the generation of smell situated in the nasal cavity which constitute part of the olfactory system. Inside the nasal cavity, the turbinates direct the inspired air toward the olfactory epithelium in the upper posterior region, the surface of which is covered by a mucus layer. Though only a few centimeters wide, there are an estimated 6,000,000 bipolar olfactory receptor cells (or neurons) inside the olfactory epithelium. There are about 347 related and various olfactory receptor types and a typical receptor cell contains only one type. Astonishingly, one cell is responsible for a range of odorants, the reason for which will be discussed in the later part. The olfactory cells step into the olfactory mucus with 10-30 receptor bearing cilia, and extend a long axon through the epithelium and cribriform plate to the olfactory bulb, a signal relay center.
For detection, odorants, essentially volatile and non-reacting chemicals, have to pass through the 10–40μm thick mucus layer, which is achieved by either diffusion or the aid of odorant binding proteins which escort lipophilic molecules through the aqueous mucus medium. Note that the mucus, mainly secreted by Bowman’s glands, contains a number of enzymes which can kill bacteria and inactivate virus. The odorant then come into contact with one of the many cilia and absorbed onto one of the receptors at the extracellular–intracellular interface.
Upon recognition, the odorant is the first messenger. The occupied receptor, G-protein-coupled receptor (GPCRS), activates a GTP-binding protein, which in turn activates type III adenylyl cyclase, catalyzing the production of 3′,5′-cyclic monophosphate (cAMP). The second messenger process then initializes with cAMP inducing the opening of a cyclic nucleotide-gated channel, controlling an influx of Na+ and Ca2+ ions and depolarization of the receptor cell. Subsequently, Ca2+ ions act as third messengers that activate the flow of Cl− ions which further amplifies this initial depolarization and trigger an electronic impulse in the olfactory sensory neuron.
An interesting point to note is that, the brain may be under the threat of direct viral and xenobiotic invasion, which can effectively bypass the blood brain barrier due to the direct projection of the receptor neurons from the nasal cavity into the brain. Nonetheless, within the lamina propria, the unmyelinated axons of the receptor neurons bundles together with unit each contain about 200 axons and is surrounded by olfactory ensheathing cells (OECs). Between the OECs, there is a significant population of microglia and macrophages for protection. The bundles are further encapsulated by olfactory nerve fibroblasts (ONFs) to form the olfactory nerve (CNI) fascicles which finally enter into the cribriform plate.
The signal generated in the receptor cell goes to the brain via the neuron through the cribriform plate, and finally terminate at the olfactory bulb locating at the base of the brain directly over the cribriform plate. The bulb is of complex structure and perform the final stage of signal processing before the signals are relayed to the olfactory cortex in the brain. Upon completion of this cycle, a sense of smell is generated.
Discussion
You may wonder, why it is mentioned in the introduction, up to now the complete picture of the generation of sense smell is not known. The conundrum being, what actually activates the receptor for an impulse to be generated? Why can a receptor be responsible for a range of odorants? There exists several theories pinpointing this matter.
Traditionally, scientists used the key-and-lock theory purported in 1963 by Amoore which states that molecules of a particular shape can fit into a particular receptor. This theory works in many enzymatic action but not in this case as physiological studies of rodent olfactory receptor neurons showed olfactory cells respond to many odorants of different shapes.
Mori & Shepard later proposed the ‘odotope theory’, an alternative version on the lock and key model. It states that the receptor recognize and respond to key features, for instance, the functional groups, of the odorant in lieu of the whole shape. Whether the atoms are present is more important in this theory than the position of the atoms. The ‘combinatorial code’ nature of odorant signaling is addressed as one odorant can activate several receptor types and conversely, one type can respond to several odorants. However, chiral molecules such as enantiomer pairs may smell different in their mirror image forms. Should the receptors detect individual groups contained on the molecule rather than the whole molecule as a whole, mirror image forms of molecules should smell the same as they chemically contain the same functional groups and atoms, though with different spatial configuration.
Besides, there exist a theory that the vibrational spectrum of a molecule defines its smell, which, again, is turned down by the fact that mirror image molecules should give the same smell due to the same spectrum.
Riding on the tide of the advancement in Physics, Turin proposed a molecule vibrational theory utilizing quantum mechanics in 1996. A news in BBC dated 28, Jan, 2013 quoted Turin’s "There are many, many problems with the shape theory of smell - many things it doesn't explain that the vibrational theory does." While many scientists still do not give it a green light due to the lack of valid scientific substantiation, he insists the theory can explain the loophole of the widely accepted shape-dependent theory.
Despite the efforts by scientists, still, the question what actually activates the receptor for an impulse to be generated is still unsolved. To me, Turin’s theory is appealing, but not convincing enough. After all, a theory must be supported by evidence for it to be valid. Somehow, Turin has opened the door and given scientists subtle insights on the route of investigation.
Conclusion
For just a simple fragrant that we take for a grant, numerous biochemical processes are behind the scene. The picture is not yet fully unveiled but it is unquestionably in progress. Notwithstanding, with continued research and experiment, it is likely to see the real picture in the not too distant future.

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