In most mammals, pheromones are detected using a dual olfactory system (Figure 1.5). This olfactory system consists of the main olfactory system (MOS) and the accessory olfactory system (AOS). Mammals use either one or both of these system to detect chemosensory clues present in scent marks. The main olfactory epithelium (MOE) is responsible for the conscious perception of odours while the accessory olfactory system is responsible for the detection of pheromones that elicit various behavioural and physiological responses between conspecifics.
1.5.1 Main olfactory system
The MOE is located at the posterior end of the nasal cavity and is mostly made up of olfactory sensory neurons (OSNs). These OSNs send their axons into the main olfactory bulb (MOB) which in turn sends out nerve fibres to the olfactory cortex
Chapter 1: Introduction
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before proceeding to higher sensory centres. The OSN contain olfactory receptors which are heptahelical G-protein-coupled receptors (GPCR) that share a significant homology in vertebrates (Rouquier and Giorgi, 2007). The amount of receptors varies between mammals depending on how much olfactory system is required for survival. For instance, humans contain less functional olfactory receptor genes than most other mammals. A rise in pseudogenes from old world monkeys to new world monkeys suggests primates may have lost part of their olfactory ability over time (Rouquier et al., 2000). In contrast to this mice and rats have over 1300 olfactory receptors that bind a broad range of odorants with different affinities (Zhang and Firestein, 2002).
The MOS is not normally associated with pheromone detection; it is usually responsible for detection and differentiation of complex chemical signals that are present in both the physical and social surroundings of individuals. However the individual sensory roles for the two olfactory systems are still unclear. Pheromone detection by the MOS has been reported in female boars. Male boars secrete a volatile steroid androstenone in their saliva that induces lordosis in females (Dorries
et al., 1995; Dorries et al., 1997). If the female AOS is blocked off the pheromone continues its effect inducing the female mating stance, suggesting this volatile is detected in the MOS (Dorries et al., 1995; Dorries et al., 1997). Also preovulatory LH surge and ovulation in ewes after exposure to ram odours is thought to involve the MOS. The ewes still experience a surge in LH in response to the rams after blocking off the AOS (Cohen-Tannoudji et al., 1989; Delgadillo et al., 2009). (methylthio) methanethiol (MTMT) in male mouse urine is also detected by the MOS (Lin et al., 2005). The rabbit mammary pheromone 2-methylbut-2-enal present in the milk of the mother encourages nipple-searching behaviour in pups. Removal of the AOS has no affect on the pups’ nipple-searching efforts but removal of the MOE eliminates the behaviour completely (Hudson and Distel, 1986).
21 Main olfactory epithelium
(MOE)
Gruenberg ganglion (GG)
Vomeronasal organ (VNO)
Septal organ of Masera (SO)
Accessory olfactory bulb (AOB)
Main olfactory bulb (MOB)
Figure 1.5 Anatomical representation of the mammalian olfactory system.
The location of the various chemosensory subsystems in the mammalian nose. A rodent was used in this example. Adapted from Brennan and Zufall , 2006.
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1.5.2 Accessory olfactory system
The AOS is responsible for the detection of the majority of pheromones. A vomeronasal organ (VNO) is based in the vomer between the nose and the mouth and is responsible for detecting stimuli. Like the MOE, the VNO contains sensory receptors whose axons project into the accessory olfactory bulb (AOB). The axons that leave the AOB project into parts of the brain that stimulate aggression and mating behaviour.
The VNO contains two types of sensory receptor – VR1 and VR2 receptors. VR1 receptors detect small volatile molecules and VR2 receptors perceive involatile pheromones such as peptides and proteins (Dulac and Axel, 1995; Matsunami and Buck, 1997). Both receptors belong to two distinct super families of seven trans membrane G-protein coupled receptors. They have different molecular structures and are expressed in different locations in the VNO. VR1 receptors are linked to the G protein Gαi2 and are located in the apical region of the VNO. VR2 receptors are liked to a G protein Gαo and are based in the basal compartment of the VNO (Dulac and Torello, 2003; Mombaerts, 2004). They have a longer N terminal which is thought to be involved in pheromone binding. The V1R receptors transmit projections into the rostral part and the V2Rs into the caudal part of the AOB (Zufall and Leinders-Zufall, 2007).
Identification of VR1 genes has been made easier because of their relatively simple gene structure. At present a complete VR1 gene repertoire has been identified in human, chimpanzee, mouse, rat, dog, cow and opossum with the number of intact genes varying between species (Rodriguez and Mombaerts, 2002; Rodriguez et al.,
2002; Grus and Zhang, 2004; Zhang et al., 2004; Young et al., 2005; Grus et al.,
2005). However little is known about VR2 receptors and until recently these receptors had only been described in rodents and marsupials. The first functional VR2 receptor genes in a primate, the gray mouse lemur, were observed in a study by Holenbrink et al., 2012.
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Many mammals exhibit the Flehmen response to transfer information to their VNO. This involves the animal curling back its upper lip and exposing its front teeth. The animal then inhales over the scent and remains in that position for a few minutes to allow air to transfer from the scent mark to the VNO. In cattle blocking of the VNO significantly reduces inter-individual aggression between males (Klemm et al.,
1984). Removing the VNO in male mouse lemurs reduces aggression between males and reduces sexual behaviours (Aujard, 1997). Ewes could not distinguish their own lambs from lambs belonging to others after their VNO was purposely blocked (Booth and Katz, 2000) however conflicting evidence was published by Levy
et al., 1995. VNO- dependant pheromone responses in rodents have been studied in more detail and include:
The Lee-Boot effect – the grouping of female mice in one area causes suppression or a modification of estrous (Van der Lee and Boot, 1955)
The Vandenbergh effect – the onset of puberty in young female mice is accelerated by non-volatile molecules in adult male urine (Vandenbergh, 1969)
The Bruce-Lee effect – the presence of a male (or his urine) from a different strain to her mate can prevent egg implantation in females that have recently mated (Bruce, 1960)
The Whitten effect – synchronised estrous in a group of females in response to urinary cues from a male conspecific (Whitten, 1958)