1.6.1.1.1 Odorants
An odour is the sensory stimulation from a group of molecules that are airborne and travel to the olfactory epithelia, located in the roof of the nasal cavities in the nose, for detection by the nasal receptors. Not all molecules possess the properties to enable them to be odorants (Stoddart, 1976). In order to be an odorant a molecule or group of molecules has to be volatile, have a low molecular mass (below 350 Daltons) and have a high vapour pressure (Ohloff, 1986). They also have to have relatively low
polarity in order to travel through the lipid-rich nasal mucosa to the epithelium, where they can bind to nasal receptors (Ohloff, 1986). EO molecules are generally low molecular mass volatiles with these properties (Lamparsky & Müller, 1994; Kohlert et al., 2000). The olfactory sense is able to distinguish among a practically infinite number of chemical compounds at very low concentrations (Firestein, 1996; Mombaerts, 1999).
1.6.1.1.2 Olfactory pathways
The nose is an external structure on the head of most mammals and the nasal cavity is usually bilaterally symmetrical, bisected by a septum. In mammals, this olfactory organ is incorporated into the respiratory system. Structurally, the nose is designed to inhale odours, although it is the olfactory nerve, cranial nerve 1, which is responsible for the sense of smell (Kandel, Schwartz, & Jessell, 2000). In order to facilitate odour-detection, sniffing takes place, drawing the volatilised odour molecules up the nose to the olfactory epithelium where the odour molecules can bind to the olfactory receptors of cranial nerve 1. This in turn facilitates detection and identification of the odour, although even without sniffing odorants can still be detected (Sobel et al., 1998).
The olfactory epithelium is situated at the top of the nasal cavity. In humans, this area is about 5cm2 whereas in rodents it is much larger (Dodd & Squirrell, 1980; Engen, 1982). The nasal epithelium contains the sensory cells also known as the olfactory receptor cells. It is bathed in mucus, which contains water, mucopolysaccharides, immunoglobins (IgA) and proteins (which include enzymes such as lysozyme, and other peptidases and xenophobic agents). Some processing of odour molecules takes place here by the enzyme molecules. The lipids in the mucus assist in the transport of the odorants to the olfactory receptor molecules; only molecules that are soluble in the mucus will reach the olfactory receptors (Dodd & Squirrell, 1980).
The sensory cells, or olfactory nerve cells (cranial nerve 1), are bipolar neurons that are unique in that they can regenerate (Graziadei, Levine, Monti Graziadei, 1978). Each one is likely to express only one type of receptor but one odour molecule could activate more than one kind of receptor. In humans there are approximately 10
million receptor molecules and in dogs there are approximately 200 million (Engen, 1982). In 1991, Axel and Buck discovered a family of roughly 1000 genes that encode the odour receptors (Axel, 1995). In humans and mice, this comprises 1-2% of the total number of genes, second only to the immune system. This family of olfactory receptor genes is part of an even larger group of proteins called G protein- coupled receptors. G proteins, so named because they derive energy from the hydrolysis of guanosine triphosphate (GTP), sit below certain types of receptors that cross the cell membrane (Gilman, 1987). When an odorant binds to a specific odorant receptor, it triggers the G (olf) protein to stimulate adenylate cyclase type III to synthesize cAMP. cAMP in turn opens a cyclic nucleotide gated cation channel, allowing an influx of Ca2+ ions to open the Ca2+ activated chloride channel. This leads to an influx of chloride ions and depolarization of the olfactory neuron (Bhandawat, Reisert, & Yau, 2005).
Each olfactory neuron cell has hundreds of olfactory receptors situated on non-motile cilia, which project into the mucus. The other end of the sensory cell, the axon, projects into the olfactory bulb at the front of the brain and terminates in structures called glomeruli, which are nerve junctions containing numerous synapses. A given receptor-type projects to one or at most a few glomeruli. The olfactory bulbs are elongated paired structures at the anterior (front) inferior (underneath) surface of the cerebral hemispheres. There are two olfactory bulbs lying on each side of the centre of the brain. The olfactory receptors in the nose project to the ipsilateral (same hemispheric side of the brain) mitral and tufted cells that form the glomeruli in the olfactory bulb. The axons of the mitral and tufted cells form the lateral olfactory tract; this projects to the olfactory cortex and via the anterior commissure to the other olfactory bulb. The mitral cell axons project ipsilaterally to the olfactory cortex, whereas the axons of the tufted cells are responsible for the connection between the two bulbs, allowing feedback control of the signal between the two olfactory bulbs (Engen, 1982; Savic & Gulyas, 2000; Savic, 2001).
The olfactory cortex consists of the anterior olfactory nucleus, the piriform cortex, the periamygdaloid and the transentorhinal cortex. The olfactory tract connects directly to the periamygdaloid cortex, while the olfactory tubercle connects to the mediodorsal thalamic nucleus. Additionally, the third neuron in the olfactory pathway projects from the olfactory cortex and the amygdala to the orbitofrontal cortex, the
subiculum, the thalamus, the hypothalamus, the brain stem, and, the caudate nucleus. All of these structures are involved in the processing of emotions and emotional information (Royet et al., 2001; Savic, 2001; Davis & Eichenbaum 1999; Zald & Pardo, 1997; Kalin, Shelton, & Davidson, 2007; Royet et al., 2001; Savic et al., 2000; Zald & Kim, 1996) (see section 1.1.3.1). Likewise, there are projections back to the olfactory bulbs from most of the main structures involved in the anxiety or defence response. Concurrent with this is the olfactory bulbectomy animal model of depression, in which treatment with antidepressants alleviates the behavioural symptoms that result from removal of the olfactory bulbs (Song & Leonard, 2005; McGrath & Norman, 1998).
Unlike rodents, humans are considered to be microsomatic, meaning that humans have relatively small olfactory bulbs. Rodents are classed as macrosomatic and thought to rely heavily on smell for their normal behaviour patterns. This idea has been challenged. Keverne, (1980) and Kohl, Atzmueller, Fink, and Grammer, (2001) argued that animals with more developed brains have the capacity to have a more sophisticated sense of smell (Keverne, 1980). In addition, in primates, olfactory receptors can respond to more than one odour type, and are thought to be detected via the patterns of signalling that the odours elicit, and the olfactory bulb is hypothesised to act more as a filter than a detection system.
Interestingly, a loss of olfaction can have a major impact on human wellbeing (Doty, 2001). This could be evidence for an influence of odorants, such as EOs, on health and wellbeing, Altered sense of smell has been reported after exposure to low levels of environmental chemicals; one example of this is cacosmia, which causes the sufferer to detect foul smells even when none is present (Bell, Schwartz, Amend, Peterson, & Stini, 1994). This illness is linked to multiple-chemical-sensitivity syndrome and can cause depression and anxiety in some individuals (Bell et al., 1994). Likewise, altered sense of smell has been reported in other psychological illnesses such as schizophrenia (Purdon & FlorHenry, 2000), hysteria (Weintraub, 1973), and alcoholic Korsakoff syndrome (Hulshoff Pol et al., 2002). Furthermore, in early Alzheimer’s disease, olfaction is impaired and this might be an early marker of the disease (Kovacs, Cairns, & Lantos, 2001). Loss of olfaction has also been reported in HIV patients (Graham, Graham, Bartlett, Heald, & Schiffman, 1995) and in Parkinson’s disease (Hawkes, Shephard, & Daniel, 1997).
It is also of interest that linalool interacts with adenyl-cyclases in in-vitro studies (Lis-Balchin & Hart, 1999 and see previous section), and cAMP is the most abundant second messenger in the olfactory neurons.