Vomeronasal Research Articles

Horses are Obligate Nasal Breathers: But does this Obligation Still Apply when a Horses ‘Nasopharyngeal Air Supply’ and with this its ‘Defence through Flight’, is Compromised

It had been suggested that obligate nasal breathing had evolved to enhance a horses ability to detect predator scents whilst grazing. The singular opening of the vomeronasal organ into the nasal cavity had certainly developed in a manner that supported this form of breathing and thence theory. A horses ability to carry feed in its mouth, without this being drawn into the airway during flight, was another theory put forward to explain this obligation. The horse as a species is heavily reliant on flight as a means of defence and thence survival. Any reduction in nasopharyngeal patency would logically compromise a horses ability to maintain acceleration and thence its ability to evade a predator. The likelihood that a horse would elect to supplement a compromised nasal air supply with orally inspired air whilst fleeing a predator, seemed logical. Nasopharyngeal and upper tracheal intraluminal pressure measurements recorded during periods of intermittent dorsal displacement of the soft and experimentally induced palatal instability indicated that air was being acquired orally in these situations. Keywords: Palatal instability, mouth breathing, oropharyngeal seal, palatal instability, dorsal displacement of the soft palate. Read more →

Strike-Induced Chemosensory Searching in Reptiles: A Review

Chemosensory searching in squamates with specialized tongue–vomeronasal systems is well-documented. By tongue-flicking, these reptiles gather important chemical cues from their environment to guide their feeding behavior. Strike-induced chemosensory searching (SICS) is a specific expression of chemosensory reception that is central to the predatory strategy used by venomous reptiles that strike, release, and relocate their prey. This complex behavioral process consists of multiple sequential steps and has been mainly studied in viperids, particularly rattlesnakes. Although this phenomenon has been extensively researched, there is no comprehensive review of the SICS literature. Here, we provide such a review, centered on the idea that SICS is a result of suppression, and then enhancement, of chemosensory searching that serves as a key element of the ambush hunting strategy that most viperid snakes use to consume large and well-defended prey. SICS is also present in other venomous and nonvenomous taxa, and we include a taxonomic categorization of SICS studies in our review. We summarize the key findings discovered during decades of research into this remarkable feeding behavior and highlight areas where our knowledge remains incomplete in an effort to foster further research that will increase our understanding of reptilian feeding ecology.

The Effects of Androstenone on the Plasma Serotonin, β-Endorphin, and Cortisol Concentrations in Thoroughbred Horses.

Simple SummaryThe development of horse managing tools is needed to prevent accidents and to improve welfare for domestic horses because the safety hazards for people who are exposed to horses are well documented. Androstenone, a pheromone secreted from boars, changes the behavior of dogs to become less excited. In horses, a previous study showed that a specific receptor for androstenone was expressed in the vomeronasal organ and nasal cavity. Horses treated with androstenone also showed more compliant behaviors. Thus, this study was conducted to investigate the mechanism of androstenone for changing horse behaviors. The change in the plasma concentrations of serotonin, β-endorphin, and cortisol in response to the treatment of androstenone was evaluated using an immunoassay. The results of this study demonstrated that androstenone may control the neuroendocrine system of horses, resulting in behavioral changes. This is the first work that studies the mechanism of pheromone treatment in horses and can be applied for further study about the effect of pheromone therapy on horses.Androstenone influences the changing behaviors of animals. Previous studies discovered that an androstenone receptor was expressed in horses and treatment with androstenone induced horses to be more compliant. As changes in the level of neuroendocrine factors result in animal behavioral changes, the objective of the study was to monitor the changes in the concentrations of 5-HT, β-endorphin, and cortisol in response to androstenone. Eight thoroughbred horses (five mares and three geldings) were treated with androstenone diluted in jojoba oil (10 µg/mL) and only oil for a control cross-overly. A handler applied the treatments to the horses′ nostril and rubbed for 5 s. Blood samples were collected before, 15, 30, and 60 min after each treatment. The concentrations of each neurotransmitter were analyzed by enzyme-linked immunosorbent assay. The concentrations of each neurotransmitter after the treatment were compared to its baseline concentration. The concentration of 5-HT of the androstenone-treated horses remained consistent throughout the experiment, while the concentration of the control group significantly decreased over time. The plasma concentration of β-endorphin in the androstenone-treated group also remained constant, whereas the concentration increased in the control group. Cortisol levels did not change in either the treated or untreated groups. An androstenone treatment triggers changes in the secretion of 5-HT and β-endorphin in horses.

Loss-of-function variants in SEMA3F and PLXNA3 encoding semaphorin-3F and its receptor plexin-A3 respectively cause idiopathic hypogonadotropic hypogonadism

PurposeIdiopathic hypogonadotropic hypogonadism (IHH) is characterized by absent puberty and subsequent infertility due to gonadotropin-releasing hormone (GnRH) deficiency. IHH can be accompanied by normal or compromised olfaction (Kallmann syndrome). Several semaphorins are known potent modulators of GnRH, olfactory, and vomeronasal system development. In this study, we investigated the role of Semaphorin-3F signaling in the etiology of IHH. MethodsWe screened 216 IHH patients by exome sequencing. We transiently transfected HEK293T cells with plasmids encoding wild type (WT) or corresponding variants to investigate the functional consequences. We performed fluorescent IHC to assess SEMA3F and PLXNA3 expression both in the nasal region and at the nasal/forebrain junction during the early human fetal development. ResultsWe identified ten rare missense variants in SEMA3F and PLXNA3 in 15 patients from 11 independent families. Most of these variants were predicted to be deleterious by functional assays. SEMA3F and PLXNA3 are both expressed along the olfactory nerve and intracranial projection of the vomeronasal nerve/terminal nerve. PLXNA1-A3 are expressed in the early migratory GnRH neurons. ConclusionSEMA3F signaling through PLXNA1-A3 is involved in the guidance of GnRH neurons and of olfactory and vomeronasal nerve fibers in humans. Overall, our findings suggest that Semaphorin-3F signaling insufficiency contributes to the pathogenesis of IHH.

Morphological and Histological Features of the Vomeronasal Organ in African Pygmy Hedgehog (Atelerix albiventris).

Simple SummaryHedgehogs have a sensitive olfaction, but little is known about their vomeronasal organ, which detects specific chemicals such as pheromones. This is the first study to reveal the morphological and histological features of the vomeronasal organ in the African pygmy hedgehog. Notably, unlike other mammals, the hedgehog has a large, well-developed serous gland in the vomeronasal organ. This gland seems to allow flushing out odorous substances from the vomeronasal organ and might be favorable for subsequent stimulus reception.The vomeronasal organ (VNO) detects specific chemicals such as pheromones and kairomones. Hedgehogs (Eulipotyphla: Erinaceidae) have a well-developed accessory olfactory bulb that receives projections from the VNO, but little is known about the hedgehog VNO. Here, we studied the histological features of the VNO in five individual African pygmy hedgehogs by hematoxylin-eosin, periodic acid-Schiff, and Alcian blue stains. The hedgehog VNO comprises a hyaline cartilage capsule, soft tissue and epithelial lumen, and it branches from the site just before the incisive duct opening into the nasal cavity. The soft tissues contain several small mucous (or mucoserous) glands and a large serous gland, and many venous sinuses all around the lumen. The VNO lumen is round to oval throughout the hedgehog VNO, and the sensory epithelium lines almost the entire rostral part and medial wall of the middle part. These findings indicate that the VNO is functional and plays an important role in the hedgehog. Notably, the VNO apparently has a characteristic flushing mechanism with serous secretions like those of gustatory glands, which the hedgehog might frequently use to recognize the external environment.

Analysis of the vomeronasal organ transcriptome reveals variable gene expression depending on age and function in rabbits

The vomeronasal organ (VNO) is a chemosensory organ specialized in pheromone detection that shows a broad morphofunctional and genomic diversity among mammals. However, its expression patterns have only been well-characterized in mice. Here, we provide the first comprehensive RNA sequencing study of the rabbit VNO across gender and sexual maturation stages. We characterized the VNO transcriptome, updating the number and expression of the two main vomeronasal receptor families, including 128 V1Rs and 67 V2Rs. Further, we defined the expression of formyl-peptide receptor and transient receptor potential channel families, both known to have specific roles in the VNO. Several sex hormone-related pathways were consistently enriched in the VNO, highlighting the relevance of this organ in reproduction. Moreover, whereas juvenile and adult VNOs showed significant transcriptome differences, male and female did not. Overall, these results contribute to understand the genomic basis of behavioural responses mediated by the VNO in a non-rodent model.

Field evidence supporting monitoring of chemical information on pathways by male African elephants

When animals move along well-established pathways, sensory cues along the path may provide valuable information concerning other individuals that have used the same route. Yet the extent to which animals use pathways as sources of public social information is poorly understood. Here we quantified the responses of wild African savannah elephants, Loxodonta africana , to olfactory information along natural elephant pathways, habitual routes that link predictable critical resources in the environment. By monitoring the behaviour of elephants travelling on pathways in a predominantly male study population, we found that elephants were highly olfactorily responsive to pathway substrate. Lone travellers were more responsive than elephants travelling in groups, suggesting elephants without social companions may be more dependent on olfactory cues on pathways during navigation. Furthermore, by experimentally presenting olfactory cues on pathways we found that male African elephants exhibited focused olfactory responses to urine cues of same-sex conspecifics for at least 48 h from time of deposition, and that urine from adult elephants was more likely to elicit vomeronasal system responses than subadult urine. African elephants may therefore potentially be able to discern the age and maturity of individuals they can expect to encounter in the environment from remote urine cues on pathways. We suggest elephant pathways act as a public information resource, assisting navigating elephants via the depositing of urine and dung by previous travellers on the route. These results could help inform elephant management, which may manipulate olfactory information on pathways in high human–wildlife conflict areas, or could use olfactory urine cues to improve the efficiency of corridors that link protected areas for elephants. • Male elephants use the olfactory sense extensively when travelling on pathways. • Those travelling alone are more responsive to pathways than group travellers. • Olfactory responses are made to urine for at least 48 h after it is deposited. • Adult urine elicits vomeronasal system responses more than subadult urine.

Histological and Immunohistochemical Characterization of Vomeronasal Organ Aging in Mice.

Simple SummaryChemical communication has been intensely studied and the importance of its role in animal life has been ascertained. Located in the nasal cavity, the vomeronasal organ is one of the main actors in charge of chemical reception. Alterations of this organ have proven to modify behavioral responses to semiochemical expositions. For all the other organs, a well-known origin of alteration is aging. The objective of this study was to analyze this effect on the vomeronasal organ condition and to determine the nature of these potential changes. This study demonstrates that this organ is significantly impacted by aging. In particular, old mice present strong signs of neuronal degeneration compared to adults.The vomeronasal organ (VNO) plays a crucial role in animal behavior since it is responsible for semiochemical detection and, thus, for intra- and interspecific chemical communication, through the vomeronasal sensory epithelium (VNSE), composed of bipolar sensory neurons. This study aimed to explore a well-recognized cause of neuronal degeneration, only rarely explored in this organ: aging. Murine VNOs were evaluated according to 3 age groups (3, 10, and 24 months) by histology to assess VNSE changes such as cellular degeneration or glycogen accumulation and by immunohistochemistry to explore nervous configuration, proliferation capability, and apoptosis with the expression of olfactory marker protein (OMP), Gαi2, Gαo, Ki-67, and cleaved caspase-3 proteins. These markers were quantified as percentages of positive signal in the VNSE and statistical analyses were performed. Cellular degeneration increased with age (p < 0.0001) as well as glycogen accumulation (p < 0.0001), Gαo expression (p < 0.0001), and the number of cleaved-caspase3 positive cells (p = 0.0425), while OMP and Gαi2 expressions decreased with age (p = 0.0436 and p < 0.0001, respectively). Ki67-positive cells were reduced, even if this difference was not statistically significant (p = 0.9105). Due to the crucial role of VNO in animal life, this study opens the door to interesting perspectives about chemical communication efficiency in aging animals.

The Chemosensory Repertoire of the Eastern Diamondback Rattlesnake (Crotalus adamanteus) Reveals Complementary Genetics of Olfactory and Vomeronasal-Type Receptors.

Pitviper sensory perception incorporates diverse stimuli through the integration of trichromatic color vision, bifocal heat-sensing, and dual-system chemoperception. Chemoperception, or olfaction, is mediated by chemoreceptors in the olfactory bulb and the vomeronasal organ, but the true genomic complexity of the gene families and their relative contributions is unknown. A full genomic accounting of pitviper chemoperception directly complements our current understanding of their venoms by generating a more complete polyphenic representation of their predatory arsenal. To characterize the genetic repertoire of pitviper chemoperception, we analyzed a full-genome assembly for Crotalus adamanteus, the eastern diamondback rattlesnake. We identified hundreds of genes encoding both olfactory receptors (ORs; 362 full-length genes) and type-2 vomeronasal receptors (V2Rs; 430 full-length genes). Many chemoreceptor genes are organized into large tandem repeat arrays. Comparative analysis of V2R orthologs across squamates demonstrates how gene array expansion and contraction underlies the evolution of the chemoreceptor repertoire, which likely reflects shifts in life history traits. Chromosomal assignments of chemosensory genes identified sex chromosome specific chemoreceptor genes, providing gene candidates underlying observed sex-specific chemosensory-based behaviors. We detected widespread episodic evolution in the extracellular, ligand-binding domains of both ORs and V2Rs, suggesting the diversification of chemoreceptors is driven by transient periods of positive selection. We provide a robust genetic framework for studying pitviper chemosensory ecology and evolution.

Functional validation of epitope-tagged ATF5 knock-in mice generated by improved genome editing of oviductal nucleic acid delivery (i-GONAD).

Activating transcription factor 5 (ATF5) is a stress-responsive transcription factor that belongs to the cAMP response element-binding protein (CREB)/ATF family, and is essential for the differentiation and survival of sensory neurons in murine olfactory organs. However, the study of associated proteins and target genes for ATF5 has been hampered due to the limited availability of immunoprecipitation-grade ATF5 antibodies. To overcome this issue, we generated hemagglutinin (HA)-tag knock-in mice for ATF5 using CRISPR/Cas9-mediated genome editing with one-step electroporation in oviducts (i-GONAD). ATF5-HA fusion proteins were detected in the nuclei of immature and some mature olfactory and vomeronasal sensory neurons in the main olfactory epithelium and vomeronasal organ, respectively, as endogenous ATF5 proteins were expressed, and some ATF5-HA proteins were found to be phosphorylated. Chromatin immunoprecipitation (ChIP) experiments revealed that ATF5-HA bound to the CCAAT/enhancer-binding protein (C/EBP)-ATF response element site in the promotor region of receptor transporting protein 1 (Rtp1), a chaperone gene responsible for proper olfactory receptor expression. These knock-in mice may be used to examine the expression, localization, and protein-protein/-DNA interactions of endogenous ATF5 and, ultimately, the function of ATF5 in vivo.

Histological Features of the Vomeronasal Organ in New Born Lambs (Ovis aries)

Background: vomernasal organ is an auxiliary olfactory organ which located at the base of nasal septumcomposed of olfactory epithelium and being enclosed by cartilaginous capsule. The current study was aimedto investigate the histological structure of vomernasal organ in new born lamb.Methods: six heads of new born lamb were used for this study. The nasal cavity including the hard palatewas sward up into four transvers sections. The sections were processed with paraffin embedding techniqueand tissue sections were stained with H&amp;E stain.Conclusions: The rostral and middle portions of vomeronasals duct had medial and lateral walls with crescentshape lumen and enclosed completely by hyaline cartilage. The medial wall was lined with still diffentiatingneuro-epithelium, possessed many of intra epithelial capillaries and composed of supporting, bipolar neuron&amp; basal cells. The lateral wall was lined with differentiating respiratory epithelium. The lamina propriasubmucosa beneath both neuro and respiratory epithelia composed of ruminant of embryonic mesenchymaltissue contained newly formed glands, blood vessels and nerves. A significant (p&lt;0.05) difference wasrecoded between the diameters of the rostral, middle portions and caudal portion of both gender and therewere no differences between genders. The epithelial height of the neuro epithelia of the middle portion inboth gender had significant value (p&lt;0.05) in compare with epithelia of other portions.

Sensory Detection by the Vomeronasal Organ Modulates Experience-Dependent Social Behaviors in Female Mice.

In mice, social behaviors are largely controlled by the olfactory system. Pheromone detection induces naïve virgin females to retrieve isolated pups to the nest and to be sexually receptive to males, but social experience increases the performance of both types of innate behaviors. Whether animals are intrinsically sensitive to the smell of conspecifics, or the detection of olfactory cues modulates experience for the display of social responses is currently unclear. Here, we employed mice with an olfactory-specific deletion of the G protein Gαi2, which partially eliminates sensory function in the vomeronasal organ (VNO), to show that social behavior in female mice results from interactions between intrinsic mechanisms in the vomeronasal system and experience-dependent plasticity. In pup- and sexually-naïve females, Gαi2 deletion elicited a reduction in pup retrieval behavior, but not in sexual receptivity. By contrast, experienced animals showed normal maternal behavior, but the experience-dependent increase in sexual receptivity was incomplete. Further, lower receptivity was accompanied by reduced neuronal activity in the anterior accessory olfactory bulb and the rostral periventricular area of the third ventricle. Therefore, neural mechanisms utilize intrinsic sensitivity in the mouse vomeronasal system and enable plasticity to display consistent social behavior.

Histological and lectin histochemical studies in the vomeronasal organ of the Korean black goat, Capra hircus coreanae

We examined the localization of olfactory marker protein (OMP), protein gene product9.5 (PGP9.5), and glycan diversity in the vomeronasal organ (VNO) of the Korean black goat (Capra hircus coreanae) during the prenatal and postnatal periods using immunohistochemistry and lectin histochemistry. In fetal and 1-day-old goats, OMP was occasionally identified in receptor cells of the VNO sensory epithelium, and PGP9.5 was localized in both the sensory and non-sensory epithelia. In VNO from adult goats, OMP was abundant in the sensory epithelium and scarce in single cells of the non-sensory epithelium. These results suggest that OMP production is initiated in the VNO sensory epithelium (VNE) during the fetal stage, and that its activity is increased in adult VNO receptor cells and solitary cells in the non-sensory epithelium (VNSE). Furthermore, the free borders of the sensory epithelia were positive for 7 lectins, and 6 lectins were moderately and/or highly abundant in receptor cells. Supporting and basal cells, and nerve bundles had similar expression patterns. In VNE, 7 lectins were observed in the free border, and 6 in ciliated, goblet, and basal cells, and in gland acini. The intensities of WGA, LCA, and PNA were high in VSE receptor cells, and the intensity of PNA was high in ciliated cells of the VNSE. The other 3 lectins showed similar patterns throughout development. Collectively, these results confirm that the Korean black goat VNO starts developing during the late fetal stages and differentiates further after birth.

Human and Animal Studies in Craniofacial Embryology Enrich Human Postnatal Craniofacial Insight Differently

Objectives: To compare results obtained since 1970 from craniofacial embryological studies on human fetal tissues with results from similar studies performed on animal tissues and focus on how the different tissue types and methods can enrich the human postnatal craniofacial research. There are three sections: i) research on normal and pathological human fetal material, ii) animal experimental research performed on different species, and iii) comparisons of the results obtained. Human Material: On human prenatal material, normal and pathological developmental processes in the mandible, maxilla, nasal cavity, body axis, cranial base, vomeronasal organs, pituitary gland and nervous system were related to postnatal findings. Specific focus was given to pre/postnatal bridging of observations on holoprosencephaly, cleft lip/palate, Down syndrome, myelomeningocele/spina bifida, Kallmann syndrome, Turner syndrome and Fragile X syndrome. Demarcations of pathological regions in Cri du chat, Velo-cardio-Facial syndrome and Crouzon syndrome were mapped. Animal Material: Animal experimental results from studies on the notochord, gastrulation, neural crest, hindbrain, rhombomere, homeobox genes and experimentally induced malformation were presented. Comparing materials: The educational background of the scientists performing human and animal research, their postnatal clinical experience, the research materials used and the methods available for research are compared. Furthermore, the obtained findings result in a “pro et contra list” indicating what is positive and what is negative for improving postnatal human diagnostics. Conclusion: Human and animal studies in craniofacial embryology enrich human postnatal craniofacial insight differently. Future cooperation between human and animal research cultures is recommended.

Puberty is a Critical Period for Vomeronasal Organ Mediation of Socio-sexual Behavior in Mice.

Genetic disruption of the vomeronasal organ (VNO), an organ responsible for pheromone processing, drastically alters socio-sexual behavior in mice. However, it is not known whether the VNO has a role during the pubertal organizational period when sex-typical socio-sexual behaviors emerge, or if disruption of the organ in adulthood is sufficient to alter socio-sexual behavior. To bypass the lifelong VNO disruption of genetic knockout models, we surgically ablated the VNO of male and female mice either during the peripubertal period [postnatal day (PND) 28–30] or adulthood (PND 58–60), with sham controls at both ages. We ruled out anosmia via the buried food test and assessed sexual odor preferences by simultaneously exposing mice to same- and opposite-sex soiled-bedding. We then measured territorial aggression with the resident-intruder paradigm and assessed sexual behavior in response to an encounter with an estrus-induced female. Neural activity approximated by FOS-immunoreactivity along the VNO-accessory olfactory pathway was measured in response to opposite-sex odors. We found that peripubertal VNO ablation decreased sexual odor preferences and neural activity in response to opposite-sex odors, and drastically reduced territorial aggression in male mice. Conversely, adult VNO ablation resulted in subtle differences in sexual odor preferences compared with sham controls. Regardless of the VNO condition, mice displayed sex-typical copulatory behaviors. Together, these results suggest that puberty is a critical period in development whereby the VNO contributes to the sexual differentiation of behavior and neural response to conspecific odors.

Chapter 20 - The vomeronasal organ: History, development, morphology, and functional neuroanatomy

The human vomeronasal organ (VNO) is an accessory olfactory organ located on the anteroinferior part of the nasal septum, 1.5-2.5cm from the nostrils. Its main role is pheromone reception and, through its anatomical connections with the central nervous system, especially parts of the hypothalamus, modulation of both social and sexual behavior, although these relations have been established only in nonprimates and very little is yet established for the structure and function of the human VNO. Morphologically, the human VNO is a pit or duct-shaped structure, comprised of three cellular layers-basal cells, neural cells with olfactory cell morphology and immunohistochemical phenotype, and ciliated respiratory epithelium. Medially and connected to the VNO, a small nerve fiber is found that runs longitudinally to the nasal septum and is considered by some to be a distant process of the Cranial Nerve 0 or terminal nerve. In addition to pheromone reception, the human VNO has also been associated with several pathological conditions, including sinus septi nasi, posttraumatic stress disorder, and ectopic olfactory esthesioblastoma.

From immune to olfactory expression: neofunctionalization of formyl peptide receptors

Variations in gene expression patterns represent a powerful source of evolutionary innovation. In a rodent living about 70 million years ago, a genomic accident led an immune formyl peptide receptor (FPR) gene to hijack a vomeronasal receptor regulatory sequence. This gene shuffling event forced an immune pathogen sensor to transition into an olfactory chemoreceptor, which thus moved from sensing the internal world to probing the outside world. We here discuss the evolution of the FPR gene family, the events that led to their neofunctionalization in the vomeronasal organ and the functions of immune and vomeronasal FPRs.

Coding of pheromones by vomeronasal receptors.

Communication between individuals is critical for species survival, reproduction, and expansion. Most terrestrial species, with the exception of humans who predominantly use vision and phonation to create their social network, rely on the detection and decoding of olfactory signals, which are widely known as pheromones. These chemosensory cues originate from bodily fluids, causing attractive or avoidance behaviors in subjects of the same species. Intraspecific pheromone signaling is then crucial to identify sex, social ranking, individuality, and health status, thus establishing hierarchies and finalizing the most efficient reproductive strategies. Indeed, all these features require fine tuning of the olfactory systems to detect molecules containing this information. To cope with this complexity of signals, tetrapods have developed dedicated olfactory subsystems that refer to distinct peripheral sensory detectors, called the main olfactory and the vomeronasal organ, and two minor structures, namely the septal organ of Masera and the Grueneberg ganglion. Among these, the vomeronasal organ plays the most remarkable role in pheromone coding by mediating several behavioral outcomes that are critical for species conservation and amplification. In rodents, this organ is organized into two segregated neuronal subsets that express different receptor families. To some extent, this dichotomic organization is preserved in higher projection areas of the central nervous system, suggesting, at first glance, distinct functions for these two neuronal pathways. Here, I will specifically focus on this issue and discuss the role of vomeronasal receptors in mediating important innate behavioral effects through the recognition of pheromones and other biological chemosignals.

The functional relevance of olfactory marker protein in the vertebrate olfactory system: a never-ending story.

Olfactory marker protein (OMP) was first described as a protein expressed in olfactory receptor neurons (ORNs) in the nasal cavity. In particular, OMP, a small cytoplasmic protein, marks mature ORNs and is also expressed in the neurons of other nasal chemosensory systems: the vomeronasal organ, the septal organ of Masera, and the Grueneberg ganglion. While its expression pattern was more easily established, OMP's function remained relatively vague. To date, most of the work to understand OMP's role has been done using mice lacking OMP. This mostly phenomenological work has shown that OMP is involved in sharpening the odorant response profile and in quickening odorant response kinetics of ORNs and that it contributes to targeting of ORN axons to the olfactory bulb to refine the glomerular response map. Increasing evidence shows that OMP acts at the early stages of olfactory transduction by modulating the kinetics of cAMP, the second messenger of olfactory transduction. However, how this occurs at a mechanistic level is not understood, and it might also not be the only mechanism underlying all the changes observed in mice lacking OMP. Recently, OMP has been detected outside the nose, including the brain and other organs. Although no obvious logic has become apparent regarding the underlying commonality between nasal and extranasal expression of OMP, a broader approach to diverse cellular systems might help unravel OMP's functions and mechanisms of action inside and outside the nose.

Olfaction of aquatic amniotes

Amniotes originated on land, but aquatic/amphibious groups emerged multiple times independently in amniotes. On becoming aquatic, species with different phylogenetic backgrounds and body plans have to adapt themselves to handle similar problems inflicted by their new environment, and this makes aquatic adaptation of amniotes one of the greatest natural experiments. Particularly, evolution of the sense of smell upon aquatic adaptation is of great interest because receptors required for underwater olfaction differ remarkably from those for terrestrial olfaction. Here, I review the olfactory capabilities of aquatic/amphibious amniotes, especially those of cetaceans and sea snakes. Most aquatic/amphibious amniotes show reduced olfactory organs, receptor gene repertoires, and olfactory capabilities. Remarkably, cetaceans and sea snakes show extreme examples: cetaceans have lost the vomeronasal system, and furthermore, toothed whales have lost all of their olfactory nervous systems. Baleen whales can smell in the air, but their olfactory capability is limited. Fully aquatic sea snakes have lost the main olfactory system but they retain the vomeronasal system for sensing underwater. Amphibious species show an intermediate status between terrestrial and aquatic species, implying their importance on understanding the process of aquatic adaptation. The olfactory capabilities of aquatic amniotes are diverse, reflecting their diverse phylogenetic backgrounds and ecology.