Chapter 20 - The vomeronasal organ: History, development, morphology, and functional neuroanatomy
Introduction
The vomeronasal organ (VNO) is an underresearched structure (D’Aniello et al., 2017). Nowadays, it is assumed to serve as an accessory olfactory structure involved in pheromone perception (Trotier, 2011), but previously, the vomeronasal organ was widely rejected by the scientific community due to a dogma put forward by Ludwing Lewin Jacobsen, whose name has been epitomized with the VNO and anglicized as Jacobson, hence Jacobson's organ (Young and Stoyanov, 2018). Jacobsen is often credited as the scientist who discovered the VNO, but in fact, his research took place long after Frederik Ruysh in 1703 first described a blind saccular opening on the anteroinferior side of the nasal septum, while dissecting the head of a young male human cadaver—the first time such a structure had been depicted in all Animalia classes (Stoyanov et al., 2018; Young and Stoyanov, 2018). Following this discovery, a similar structure, despite its varying size and connection to other anatomical structures, was described in many other vertebrates (Stoyanov et al., 2018).
Jacobsen did indeed spend the majority of his scientific career on studying the VNO, although he never investigated the structure in primates and humans, as he noted that the higher up in the evolutionary chain, he examined the organ, the smaller its size was. Jacobsen stated that “it is most developed in the rodents, next in the ruminants. The carnivores have less, and in monkeys, it becomes so small that we are prepared to see it vanish completely in man,” leading to the widespread persuasion to this day that such a structure as the VNO does not exist in humans (Young and Stoyanov, 2018). Interestingly, this quote is often known and cited among peers as the reason the structure is often omitted and denied among scholars; however, Jacobsen as a highly educated scholar was aware of the presence of the structure in humans, despite his lack of belief it had any functions, saying that “humans, who possess a very well developed sense of taste, have only a rudiment of the organ” (Young and Stoyanov, 2018). Unlike most other structures, it is important, when discussing the human VNO, to distinguish it from other mammalian and nonmammalian VNO’s, based not only on the poorly mismatched structural and functional studies but also on the lack of an accessory olfactory bulb (AOB) in humans, which is the main neural projection of the VNO in all nonprimates (Stoyanov et al., 2018; Stoyanov and Matev, 2018).
Section snippets
Gross Morphology
Several different studies have shown that the vomeronasal organ is indeed present as a gross structure in the human body, despite its variable incidence (Gaafar et al., 1998). Most of these studies have concluded that at least one-third of the population has a structure complying with the morphology of a VNO, in most cases unilaterally, predominantly on the left side of the nasal septum (Stoyanov et al., 2016).
The VNO can be visualized as a small pit or opening of a submucosal duct about 1.5–2.5
Histology
Although well defined in other species, the human VNO has been understudied histologically. The structure, best studied from fetal cases, presents with the characteristics of the olfactory mucosa—three cellular layers, the first basal layer with two cellular components of small cells with hyperchromic nuclei (reserve cells) and larger cells with a nucleolus and cytoplasmic granulations (ganglion cell morphology), a second layer of cells with olfactory receptor morphology (single nucleolus) and
Electron Microscopy
Few studies have investigated the human VNO utilizing electron microscopy. However, all of them concluded that the functional cohort of cell—esthesiocytes contain numerous neurosecretory granules and neurofilaments, arranged in a manner indicative of basal transport of these granules (Stensaas et al., 1991; Jahnke and Merker, 2000).
Neuroanatomy and Connections to the Hypothalamus
Unlike in other species, where the VNO is innervated by a nerve projection of the accessory olfactory bulb, this structure is absent in humans, which raises further questions about the functionality of the human VNO. However, as seen in Fig. 20.8, there is indeed a nerve connection projecting to the VNO and it has been hypothesized that the “vomeronasal nerve” is a distant projection of the Terminal nerve, also referred to as Cranial Nerve 0 (or Cranial Nerve Z, see also Chapter 21 in this
Function
Although the functional aspects of the VNO in humans have so far been poorly studied and understood, numerous studies, including those focusing on identification of VNO specific genes, have been carried out in other mammals, predominantly rodents (Fig. 20.11) (Kaneko et al., 1980). Based on its morphology, the VNO is a chemosensory organ, constructed similarly as the main olfactory mucosa. Other than IHC and enzymocytochemistry, the electovomeronazogram (EVNG), despite not being performed in
Role in Social Behavior
Apart from its function as olfactory organ, the VNO has been associated with several neuropsychological disorders (Daniels and Vermetten, 2016; Bedwell et al., 2018; Houghton et al., 2019).
Olfactory stimuli have long been known as triggers of memories (McGann, 2017). One of the best-known examples of these is the so-called Proust phenomenon or Proustian memory, named after the famed French author Marcel Proust (1871–1922) (Chu and Downes, 2000; Toffolo et al., 2012; Bray, 2013). The smell of a
Role in Some Pathological Processes
Another area where the VNO can be viewed as a pathogenic factor is the formation of the sinus septi nasi—pneumatization of the nasal septum, which may lead to severe deviation and septal malformation (Mladina et al., 2017). Although the pathophysiological mechanism has not yet been proven, it is suggested than the VNO has at least in some capacity a pumping function, which, together with its close relationship with the nasal septum, may in time lead to the pneumatization of the septum. Several
Malignancies
Apart from its relation to these processes, the VNO is also involved in malignant transformation (Wormald et al., 2011). The condition is generally considered in the group of neuroblastoma malignancies and may be referred to as olfactory neuroblastoma, olfactory neuroepithelioma, or esthesioblastoma (Wormald et al., 2011). Generally, the condition is considered rare, with an incidence of 0.4 annual cases per million capita, or little more than 2% of all sinonasal malignancies (Yu et al., 2004;
Future Directions
As most of the data gathered on the human VNO is incomplete at best and based on the differences with the VNO of lower vertebrates, a complete restudying of the structure is needed to gather systematic data. These include the full gross and histological definition of the structures of the organ in fetuses and adults, as well as its neuronal projection to the CNS—independent or part of the terminal nerve. Following the proper definition of morphology and connections, the specific olfactory
Acknowledgments
The authors would like to thank Peter Valchanov, MD for his contributions to providing the three-dimensional reconstruction of the human nasal septum.
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