Peripheral oxytocin injection modulates vomeronasal sensory activity and reduces pup-directed aggression in male mice.

Behaviors are shaped by hormones, which may act either by changing brain circuits or by modifying sensory detection of relevant cues. Pup-directed behaviors have been previously shown to change via action of hormones at the brain level. Here, we investigated hormonal control of pup-induced activity in the vomeronasal organ, an olfactory sensory structure involved in the detection of non-volatile chemosignals. Vomeronasal activity decreases as males switch from a pup-aggressive state to a non-aggressive parenting state, after they socially contact a female. RNA sequencing, qPCR, and in situ hybridization were used to identify expression, in the vomeronasal sensory epithelium, of candidate GPCR hormone receptors chosen by in silico analyses and educated guesses. After identifying that oxytocin and vasopressin receptors are expressed in the vomeronasal organ, we injected the corresponding hormones in mice and showed that oxytocin administration reduced both pup-induced vomeronasal activity and aggressive behavior. Conversely, injection of an oxytocin receptor antagonist in female-primed male animals, which normally exhibit reduced vomeronasal activity, significantly increased the number of active vomeronasal neurons. These data link oxytocin to the modulation of olfactory sensory activity, providing a possible mechanism for changes in male behavior after social experience with females.

Detection of pup odors by non-canonical adult vomeronasal neurons expressing an odorant receptor gene is influenced by sex and parenting status.

BACKGROUND: Olfaction is a fundamental sense through which most animals perceive the external world. The olfactory system detects odors via specialized sensory organs such as the main olfactory epithelium and the vomeronasal organ. Sensory neurons in these organs use G-protein coupled receptors to detect chemosensory stimuli. The odorant receptor (OR) family is expressed in sensory neurons of the main olfactory epithelium, while the adult vomeronasal organ is thought to express other types of receptors. RESULTS: Here, we describe Olfr692, a member of the OR gene family identified by next-generation RNA sequencing, which is highly upregulated and non-canonically expressed in the vomeronasal organ. We show that neurons expressing this gene are activated by odors emanating from pups. Surprisingly, activity in Olfr692-positive cells is sexually dimorphic, being very low in females. Our results also show that juvenile odors activate a large number of Olfr692 vomeronasal neurons in virgin males, which is correlated with the display of infanticide behavior. . In contrast, activity substantially decreases in parenting males (fathers), where infanticidal aggressive behavior is not frequently observed. CONCLUSIONS: Our results describe, for the first time, a sensory neural population with a specific molecular identity involved in the detection of pup odors. Moreover, it is one of the first reports of a group of sensory neurons the activity of which is sexually dimorphic and depends on social status. Our data suggest that the Olfr692 population is involved in mediating pup-oriented behaviors in mice.

Immunocytochemical characterisation of ensheathing glia in the olfactory and vomeronasal systems of Ambystoma mexicanum (Caudata: Ambystomatidae).

The olfactory and vomeronasal systems of vertebrates are characterised by neurogenesis occurring throughout life. The regenerative ability of olfactory receptor neurons relies on specific glial cells, the olfactory and vomeronasal axon-surrounding cells. Numerous studies have examined mammalian olfactory ensheathing cells which are considered potential candidates for spinal cord injury repair using cell-based therapy. With regard to non-mammalian vertebrates, limited information is available on these glial cells in fish, and there is no information on them in terrestrial anamniotes, the amphibians. In the present research, we studied the immunocytochemical characteristics of axon-surrounding cells in Ambystoma mexicanum. Urodeles have relatively simple olfactory and vomeronasal systems, and represent a good model for studying ensheathing cells in extant representatives of basal tetrapods. Sections from the decalcified heads of A. mexicanum were immunocytochemically processed for the detection of proteins used in research on mammalian olfactory-ensheathing cells. S100, GFAP and NCAM were clearly observed. p75NTR, Gal-1 and PSA-NCAM showed weak staining. No vimentin immunopositivity was observed. The corresponding areas of the olfactory and vomeronasal pathways displayed the same staining characteristics, with the exception of Gal-1, p75NTR and PSA-NCAM in the mucosae. The degree of marker expression was not uniform throughout the sensory pathways. In contrast to fish, both olfactory and vomeronasal nerves displayed uniform staining intensity. This study showed that some markers for mammalian and fish-ensheathing glia are also applicable in urodeles. The olfactory systems of vertebrates show similarities, and also clear dissimilarities. Further investigations are required to ascertain the functional significance of these regional and interspecific differences.

The vomeronasal organ of Lemur catta.

The vomeronasal organ (VNO), also known as the Jacobson's organ, is a bilateral chemosensory organ found at the base of the nasal cavity specialized for the detection of higher-molecular weight (non-volatile) chemostimuli. It has been linked to pheromone detection. The VNO has been well studied in nocturnal lemurs and lorises, but poorly studied in diurnal/cathemeral species despite the large repertoire of olfactory behaviors noted in species such as Lemur catta. Here, the VNO and associated structures were studied microanatomically in one adult female and one adult male L. catta. Traditional and immunohistochemical procedures demonstrate the VNO epithelium consists of multiple rows of sensory neurons. Immunoreactivity to Growth-associated protein 43 (GAP43) indicates the VNO is postnatally neurogenic. In volume, the VNO neuroepithelium scales similarly to palatal length compared to nocturnal strepsirrhines. Numerous taste buds present at the oral opening to the nasopalatine duct, with which the VNO communicates, provide an additional (or alternative) explanation for the flehmen behavior that has been observed in this species. The VNO of L. catta is shown to be microanatomically comparable to that of nocturnal strepsirrhines. Like nocturnal strepsirrhines, the VNO of L. catta may be functional in the reception of high-molecular weight secretions.

Órgano vomeronasal: estudio anatómico de prevalencia y su función / The vomeronasal organ: anatomic study of prevalence and its role

Introducción: El órgano vomeronasal (OVN) descrito por Jacobson en mamíferos distintos al ser humano, es una incógnita tanto en lo que se refiere a su localización así como a su función en la raza humana. Se considera como un vestigio del olfato, que en los animales mamíferos parece influir en los hábitos sexuales (feromonas) y sociales. Hasta la fecha han sido escasos los estudios concluyentes al respecto en humanos. Objetivo: Conocer la prevalencia del órgano vomeronasal en nuestras consultas. Material y método: Presentamos un estudio prospectivo de prevalencia de la frecuencia de aparición de dicho órgano en 150 sujetos distribuidos por edad y sexo, explorados por endoscopia nasosinusal rígida. Por otro lado, analizamos la influencia sobre la libido (normal-disminuida-aumentada) en el posoperatorio de 35 septoplastías, a los 15 días tras retirada de taponamiento nasal y a los 30 días y lo comparamos con un grupo de 40 pacientes intervenidos timpanoplastías. Resultados: Estudiados 150 sujetos, encontramos la presencia del órgano vomeronasal en el 39,33% (59), de los cuales el 72,88% (43) fue unilateral (23 derecha y 20 izquierda) y el 27,12% (16) bilateral. En 91 (60,67%) no hallamos dicha estructura. La libido de los 35 pacientes intervenidos de septoplastía estaba disminuida, a los 15 días, en el 77,14% (27) frente al 40% (16) de las timpanoplastías, normal en el 17,14% (6) frente al 50% (20) de las cirugías otológicas, y en 2 (5,7%) poseptoplastía había aumentado, frente al 10% (4) del otro grupo. A los 30 días, en el 77,14% (27) de las septoplastías se había normalizado frente al 90% (36) del grupo otológico, en 2 (5,71%) de la cirugía nasal continuaba disminuida frente al 10% (4) del grupo de las timpanoplastías y en 6 (17,14%) tras septoplastía había aumentado. A todos los pacientes se les aplicó el mismo test no normalizado. Conclusión: El órgano vomeronasal de Jacobson continúa siendo un gran desconocido. Es una estructura que, al parecer, no es constante, al menos a la exploración endoscópica nasosinusal. Es difícil valorar si la cirugía en sí misma o el trauma psicológico posquirúrgico son los que afectan la libido de los pacientes tras la cirugía.

Introduction: The vomeronasal organ (OVN) described by Jacobson in mammals other than humans is unknown both in terms of its location and its role in the human race. It is viewed as a vestige of smell, that mammals in the animal seems to influence the sexual habits (pheromone) and social. To date, few studies have been inconclusive on this in humans. Aim: To determine the prevalence of vomeronasal organ in our medical consultations. Materials and methods: We report a prospective prevalence study of the occurrence of such a body in 150 subjects distributed by age and sex explored by endoscopic sinus rigid. On the other hand, we analyze the effect on the libido (normally less-plus) in the postoperative 35 septoplasty, 15 days after the withdrawal of nasal pack and 30 days and compared with a group of 40 tympanoplasty surgery. Results: Studied 150 subjects, we found the presence of the vomeronasal organ in 39.33% (59), of which 72.88% (43) had unilateral (23 right and 20 left) and 27.12% (16) bilaterally. In 91 (60.67%) did not find such a structure. The libido of the 35 patients who underwent septoplasty was decreased at 15 days, at 77.14% (27) versus 40% (16) of tympanoplasty, normal in 17.14% (6) compared to 50% (20) of otologic surgery, and in 2 (5.7%) postseptoplasty had increased, compared to 10% (4) the other group. At 30 days, in 77.14% (27) of the septoplasty group the libido was normalized against 90% (36) in the otologic group. In 2 cases (5.71%) of nasal surgery group was still decreased versus 10% (4) of cases of the tympanoplasty group, and in 6 (17.14%) postseptoplasty was increased. All patients were administered the same test is not standardized. Conclusion: The vomeronasal organ of Jacobson remains the great unknown. It is a structure that apparently is not constant, at least in the endoscopic sinus exploration. With regard to their role, it is difficult to assess whether the psychological trauma after surgery or the surgery by itself is responsible of the libido changes.

Deterioration of the Gαo vomeronasal pathway in sexually dimorphic mammals.

In mammals, social and sexual behaviours are largely mediated by the vomeronasal system (VNS). The accessory olfactory bulb (AOB) is the first synaptic locus of the VNS and ranges from very large in Caviomorph rodents, small in carnivores and ungulates, to its complete absence in apes, elephants, most bats and aquatic species. Two pathways have been described in the VNS of mammals. In mice, vomeronasal neurons expressing Gαi2 protein project to the rostral portion of the AOB and respond mostly to small volatile molecules, whereas neurons expressing Gαo project to the caudal AOB and respond mostly to large non-volatile molecules. However, the Gαo-expressing pathway is absent in several species (horses, dogs, musk shrews, goats and marmosets) but no hypotheses have been proposed to date to explain the loss of that pathway. We noted that the species that lost the Gαo pathway belong to Laurasiatheria and Primates lineages, both clades with ubiquitous sexual dimorphisms across species. To assess whether similar events of Gαo pathway loss could have occurred convergently in dimorphic species we studied G-protein expression in the AOB of two species that independently evolved sexually dimorphic traits: the California ground squirrel Spermophilus beecheyi (Rodentia; Sciurognathi) and the cape hyrax Procavia capensis (Afrotheria; Hyracoidea). We found that both species show uniform expression of Gαi2-protein throughout AOB glomeruli, while Gαo expression is restricted to main olfactory glomeruli only. Our results suggest that the degeneration of the Gαo-expressing vomeronasal pathway has occurred independently at least four times in Eutheria, possibly related to the emergence of sexual dimorphisms and the ability of detecting the gender of conspecifics at distance.

Transposition and Intermingling of Galphai2 and Galphao afferences into single vomeronasal glomeruli in the Madagascan lesser Tenrec Echinops telfairi.

The vomeronasal system (VNS) mediates pheromonal communication in mammals. From the vomeronasal organ, two populations of sensory neurons, expressing either Galphai2 or Galphao proteins, send projections that end in glomeruli distributed either at the rostral or caudal half of the accessory olfactory bulb (AOB), respectively. Neurons at the AOB contact glomeruli of a single subpopulation. The dichotomic segregation of AOB glomeruli has been described in opossums, rodents and rabbits, while Primates and Laurasiatheres present the Galphai2-pathway only, or none at all (such as apes, some bats and aquatic species). We studied the AOB of the Madagascan lesser tenrec Echinops telfairi (Afrotheria: Afrosoricida) and found that Galphai2 and Galphao proteins are expressed in rostral and caudal glomeruli, respectively. However, the segregation of vomeronasal glomeruli at the AOB is not exclusive, as both pathways contained some glomeruli transposed into the adjoining subdomain. Moreover, some glomeruli seem to contain intermingled afferences from both pathways. Both the transposition and heterogeneity of vomeronasal afferences are features, to our knowledge, never reported before. The organization of AOB glomeruli suggests that synaptic integration might occur at the glomerular layer. Whether intrinsic AOB neurons may make synaptic contact with axon terminals of both subpopulations is an interesting possibility that would expand our understanding about the integration of vomeronasal pathways.

The 'male effect' in sheep and goats--revisiting the dogmas.

Male-induced ovulation in sheep and goats (the 'male effect'), documented during the period 1940-1960, has long been shrouded in preconceptions concerning how, when and why it worked. These preconceptions became dogmas but recent research is challenging them so, in this review, we have re-visited some major physiological (breed seasonality; characteristics of the response; the nature of the male stimuli) and physical factors (duration of male presence; isolation from male stimuli) that affect the phenomenon. We reject the dogma that ewes must be isolated from males and conclude that male 'novelty' is more important than isolation per se. Similarly, we reject the perception that the neuroendocrine component of the male effect is restricted to anovulatory females. Finally, we re-assess the relative importance of olfactory and non-olfactory signals, and develop a perspective on the way male-induced ovulation fits with preconceptions about pheromonal processes in mammals. Overall, our understanding of the male effect has evolved significantly and it is time to modify or reject our dogmas so this field of research can advance. We can now ask new questions regarding the application of the male effect in industry and develop research so we can fully understand this biological phenomenon.

El órgano vomeronasal humano: [revisión] / Human vomeronasal organ: [revision]

El órgano vomeronasal (OVN) es una estructura que estudiamos alguna vez en anatomía, sin embargo su ubicación, frecuencia y función específica en humanos ha sido poco estudiada. Por este motivo se realizó una revisión bibliográfica actualizada acerca del OVN humano, enfatizando en puntos importantes como su anatomía y relación con algunas conductas. Hoy en día es considerado como un órgano olfatorio accesorio, capaz de percibir la presencia de vomeroferinas. Estas corresponden a un grupo de sustancias químicas identificadas, capaces de provocar cambios conductuales tanto a nivel social, sexual como maternal. Se localiza lateralmente al septo nasal y posee células periféricas, capaces de actuar como receptores, los cuales al ser estimuladas son capaces de generar una respuesta, susceptible de ser medida a través de un electrodo ubicado en el epitelio vomeronasal. Los últimos estudios sugieren que además tendría una conexión directa hacia el sistema nervioso central, mediante neuronas sensoriales bipolares, lo que implica un cuidado adicional en pacientes sometidos a cirugías cercanas a su ubicación.

The human vomeronasal organ (OVN) is a structure that is once studied in Anatomy, but commonly Iittie is known about its location, frequency and specific function. For this reason recent literature on the subject was reviewed, emphasizing important topics such as its anatomy and relation to some behaviors. The vomeronasal organ is nowadays considered an accessory olfactory organ, capable of detecting the presence of vomeropherins. These belong to a group of identified chemical substances, capable of induce behavioral changes at the social, sexual and maternal level. It is located lateral to the nasal septum, and it contains peripheral cells that act as receptors, which upon stimulation are capable of triggering a response that can be recorded via an electrode located in the vomeronasal epithelium. In addition, recent studies suggest that the vomeronasal organ has a direct connection to the central nervous system, by way of bipolar sensory neurons, which would demand additional care in patients having surgery in its vicinity.

Sexual incentive motivation, olfactory preference, and activation of the vomeronasal projection pathway by sexually relevant cues in non-copulating and naive male rats.

There are some apparently healthy male rats that fail to mate after repeated testing with receptive females. We have previously shown that these "non-copulator (NC)" males show no partner preference for a receptive female when given the opportunity to physically interact with a sexually receptive female or a sexually active male. We also demonstrated that although NC males prefer odors from estrous females to odors from anestrous females, this preference is significantly reduced in comparison to the preference displayed by copulating (C) males. The aim of the present study was to evaluate in NC males sexual incentive motivation, that is, the approach behavior of male rats to either a sexually receptive female or a sexually active male in a test where the subjects can smell, hear, and see the stimulus animal but prevents their physical interaction. In addition, we determined whether NC rats have alterations in their ability to detect odors from conspecifics or odors related to food. In the detection of odors from conspecifics, we determined if these NC males are sexually attracted toward odors from receptive females or sexually active males. For food-related odors, we quantified the time it took the subjects to locate a hidden a piece of apple. Finally, using the induction of Fos-immunoreactivity (Fos-IR) as an index of neuronal activation, we compared the response of the vomeronasal projection pathway (VN pathway) of C and NC male rats exposed to estrous bedding. Males without sexual experience (WSE) were included in all experiments to determine the importance of previous heterosexual experience in the different behavioral tests and in the activity of the VN pathway. In the sexual incentive motivation test, we found that C and WSE male rats have a clear preference for estrous females over sexually active males, whereas NC male rats showed no preference. In odor tests, our results showed that C males had a clear preference for odors from estrous females as opposed to odors from sexually active males. Although NC and WSE male rats showed a preference for estrous female odors, this preference was significantly reduced compared to that shown by C males. No differences were found between WSE, C, and NC males in the detection of stimuli associated with food-related odors. A significant increase in Fos-IR was observed in the mitral cell layer of the accessory olfactory bulb in all groups when exposed to estrous bedding. However, only the C male rats exposed to estrous female bedding showed an increase Fos-IR in all structures of the VN pathway. An increase in Fos-IR was observed in the medial preoptic area (MPOA) of WSE males exposed to estrous bedding. No increases in Fos-IR were detected along the VN pathway in NC male rats. We proposed that NC male rats do not display sexual behavior due to a reduced sexual motivation that could be caused by alterations in the neuronal activity of the VN pathway during the processing of estrous odors.

Discrimination of conspecific sex and reproductive condition using chemical cues in axolotls ( Ambystoma mexicanum).

Chemosensory cues play an important role in the daily lives of salamanders, mediating foraging, conspecific recognition, and territorial advertising. We investigated the behavioral effects of conspecific whole-body odorants in axolotls, Ambystoma mexicanum, a salamander species that is fully aquatic. We found that males increased general activity when exposed to female odorants, but that activity levels in females were not affected by conspecific odorants. Although males showed no difference in courtship displays across testing conditions, females performed courtship displays only in response to male odorants. We also found that electro-olfactogram responses from the olfactory and vomeronasal epithelia were larger in response to whole-body odorants from the opposite sex than from the same sex. In males, odorants from gravid and recently spawned females evoked different electro-olfactogram responses at some locations in the olfactory and vomeronasal epithelia; in general, however, few consistent differences between the olfactory and vomeronasal epithelia were observed. Finally, post hoc analyses indicate that experience with opposite-sex conspecifics affects some behavioral and electrophysiological responses. Overall, our data indicate that chemical cues from conspecifics affect general activity and courtship behavior in axolotls, and that both the olfactory and vomeronasal systems may be involved in discriminating the sex and reproductive condition of conspecifics.