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This study investigated the comparative morphological analysis of the vomeronasal organ and the accessory olfactory bulb in dogs and rabbits. A total of 15 heads obtained from each adult healthy Balady dog ( ) and New Zealand rabbit ( ) of both sexes. The animals were sedated and anesthetized. Then, the heads were removed for computing topography, gross, and cross-sectional anatomy and histological techniques. The vomeronasal organ was blind bilateral tubes enclosed by J-shaped cartilage on each side of the nasal septum. In dogs, it extended from the level of the upper third premolar teeth to the third incisive teeth. While in rabbits, it had no relation with the upper teeth. In cross section, the vomeronasal organ was pear-shaped in dogs and oval in rabbits. The accessory olfactory bulb was a small oval-shaped in dogs, but larger and ovoid in rabbits with clear lamination in its structure. The vomeronasal epithelium in rabbits was higher in its thickness than that of the dog. The vomeronasal duct had medial sensory and lateral respiratory epithelium. The vomeronasal glands were voluminous and of serous type in rabbits other than were seromucous in dogs. The most characteristic structural variations achieved in the vomeronasal organ and the accessory olfactory bulb of the dog and rabbit gave an indication that the organ was more functional in rabbits than in dogs. The detection and response to the pheromonal stimuli were referred to as the occurrence of olfactory epithelium in the vomeronasal organ.

In rodents, sexual behavior depends on the adequate detection of sexually relevant stimuli. The olfactory bulb (OB) is a region of the adult mammalian brain undergoing constant cell renewal by continuous integration of new granular and periglomerular neurons in the accessory (AOB) and main (MOB) olfactory bulbs. The proliferation, migration, survival, maturation, and integration of these new cells to the OB depend on the stimulus that the subjects received. We have previously shown that 15 days after females control (paced) the sexual interaction an increase in the number of cells is observed in the AOB. No changes are observed in the number of cells when females are not allowed to control the sexual interaction. In the present study we investigated if in male rats sexual behavior increases the number of new cells in the OB. Male rats were divided in five groups: (1) males that did not receive any sexual stimulation, (2) males that were exposed to female odors, (3) males that mated for 1 h and could not pace their sexual interaction, (4) males that paced their sexual interaction and ejaculated one time and (5) males that paced their sexual interaction and ejaculated three times. All males received three injections of the DNA synthesis marker bromodeoxyuridine at 1h intervals, starting 1 h before the beginning of the behavioral test. Fifteen days later, males were sacrificed and the brains were processed to identify new cells and to evaluate if they differentiated into neurons. The number of newborn cells increased in the granular cell layer (GrCL; also known as the internal cell layer) of the AOB in males that ejaculated one or three times controlling (paced) the rate of the sexual interaction. Some of these new cells were identified as neurons. In contrast, no significant differences were found in the mitral cell layer (also known as the external cell layer) and glomerular cell layer (GlCL) of the AOB. In addition, no significant differences were found between groups in the MOB in any of the layers analyzed. Our results indicate that sexual behavior in male rats increases neurogenesis in the GrCL of the AOB when they control the rate of the sexual interaction.

The olfactory system is the appropriate model for studying several aspects of neuronal physiology spanning from the developmental stage to neural network remodelling in the adult brain. Both the morphological and physiological understanding of this system were strongly supported by classical histochemistry. It is emblematic the case of the Olfactory Marker Protein (OMP) staining, the first, powerful marker for fully differentiated olfactory receptor neurons and a key tool to investigate the dynamic relations between peripheral sensory epithelia and central relay regions given its presence within olfactory fibers reaching the olfactory bulb (OB). Similarly, the use of thymidine analogues was able to show neurogenesis in an adult mammalian brain far before modern virus labelling and lipophilic tracers based methods. Nowadays, a wealth of new histochemical techniques combining cell and molecular biology approaches is available, giving stance to move from the analysis of the chemically identified circuitries to functional research. The study of adult neurogenesis is indeed one of the best explanatory examples of this statement. After defining the cell types involved and the basic physiology of this phenomenon in the OB plasticity, we can now analyze the role of neurogenesis in well testable behaviours related to socio-chemical communication in rodents.

Organisms have evolved diverse behavioural strategies that enhance the likelihood of encountering and assessing mates 1 . Many species use pheromones to communicate information about the location, sexual and social status of potential partners 2 . In mice, the major urinary protein darcin—which is present in the urine of males—provides a component of a scent mark that elicits approach by females and drives learning 3 , 4 . Here we show that darcin elicits a complex and variable behavioural repertoire that consists of attraction, ultrasonic vocalization and urinary scent marking, and also serves as a reinforcer in learning paradigms. We identify a genetically determined circuit—extending from the accessory olfactory bulb to the posterior medial amygdala—that is necessary for all behavioural responses to darcin. Moreover, optical activation of darcin-responsive neurons in the medial amygdala induces both the innate and the conditioned behaviours elicited by the pheromone. These neurons define a topographically segregated population that expresses neuronal nitric oxide synthase. We suggest that this darcin-activated neural circuit integrates pheromonal information with internal state to elicit both variable innate behaviours and reinforced behaviours that may promote mate encounters and mate selection. A neural circuit activated by the male pheromone, darcin, mediates a complex and variable array of innate and reinforced behaviours that may promote mate encounters and mate selection.

Social communication guides decision-making, which is essential for survival. Social transmission of food preference (STFP) is an ecologically relevant memory paradigm in which an animal learns a desirable food odour from another animal in a social context, creating a long-term memory 1 , 2 . How food-preference memory is acquired, consolidated and stored is unclear. Here we show that the posteromedial nucleus of the cortical amygdala (COApm) serves as a computational centre in long-term STFP memory consolidation by integrating social and sensory olfactory inputs. Blocking synaptic signalling by the COApm-based circuit selectively abolished STFP memory consolidation without impairing memory acquisition, storage or recall. COApm-mediated STFP memory consolidation depends on synaptic inputs from the accessory olfactory bulb and on synaptic outputs to the anterior olfactory nucleus. STFP memory consolidation requires protein synthesis, suggesting a gene-expression mechanism. Deep single-cell and spatially resolved transcriptomics revealed robust but distinct gene-expression signatures induced by STFP memory formation in the COApm that are consistent with synapse restructuring. Our data thus define a neural circuit for the consolidation of a socially communicated long-term memory, thereby mechanistically distinguishing protein-synthesis-dependent memory consolidation from memory acquisition, storage or retrieval. Experiments in mice show that brain circuitry centred on the posteromedial nucleus of the cortical amygdala has a key role in consolidating socially transmitted long-term memories.

Animal–animal recognition within, and across species, is essential for predator avoidance and social interactions. Despite its essential role in orchestrating responses to animal cues, basic principles of information processing by the vomeronasal system are still unknown. The medial amygdala (MeA) occupies a central position in the vomeronasal pathway, upstream of hypothalamic centers dedicated to defensive and social responses. We have characterized sensory responses in the mouse MeA and uncovered emergent properties that shed new light onto the transformation of vomeronasal information into sex- and species-specific responses. In particular, we show that the MeA displays a degree of stimulus selectivity and a striking sexually dimorphic sensory representation that are not observed in the upstream relay of the accessory olfactory bulb (AOB). Furthermore, our results demonstrate that the development of sexually dimorphic circuits in the MeA requires steroid signaling near the time of puberty to organize the functional representation of sensory stimuli. Many animals emit and detect chemicals known as pheromones to communicate with other members of their own species. Animals also rely on chemical signals from other species to warn them, for example, that a predator is nearby. Many of these chemical signals—which are present in sweat, tears, urine, and saliva—are detected by a structure called the vomeronasal organ, which is located at the base of the nasal cavity. When this organ detects a particular chemical signal, it broadcasts this information to a network of brain regions that generates an appropriate behavioral response. Two structures within this network, the accessory olfactory bulb and the medial amygdala, play an important role in modifying this signal before it reaches its final destination—a region of the brain called the hypothalamus. Activation of the hypothalamus by the signal triggers changes in the animal's behavior. Although the anatomical details of this pathway have been widely studied, it is not clear how information is actually transmitted along it. Now, Bergan et al. have provided insights into this process by recording signals in the brains of anesthetized mice exposed to specific stimuli. Whereas neurons in the accessory olfactory bulb responded similarly in male and female mice, those in the medial amygdala showed a preference for female urine in male mice, and a preference for male urine in the case of females. This is the first direct demonstration of differences in sensory processing in the brains of male and female mammals. These differences are thought to result from the actions of sex hormones, particularly estrogen, on brain circuits during development. Consistent with this, neurons in the medial amygdala of male mice with reduced levels of estrogen showed a reduced preference for female urine compared to control males. Similarly, female mice that had been previously exposed to high levels of estrogen as pups showed a reduced preference for male urine compared to controls. In addition to increasing understanding of how chemical signals—including pheromones—influence the responses of rodents to other animals, the work of Bergan et al. has provided clues to the neural mechanisms that underlie sex-specific differences in behaviors.

The feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.

Most terrestrial mammals have a vomeronasal system to detect specific chemicals. The peripheral organ of this system is a vomeronasal organ (VNO) opening to the incisive duct, and its primary integrative center is an accessory olfactory bulb (AOB). The VNO in seals is thought to be degenerated like whales and manatees, unlike otariids, because of the absence of the AOB. However, olfaction plays pivotal roles in seals, and thus we conducted a detailed morphological evaluation of the vomeronasal system of three harbor seals ( Phoca vitulina ). The VNO lumen was not found, and the incisive duct did not open into the oral cavity but was recognized as a fossa on the anteroventral side of the nasal cavity. This fossa is rich in mucous glands that secrete acidic mucopolysaccharides, which might originate from the vomeronasal glands. The olfactory bulb consisted only of a main olfactory bulb that received projections from the olfactory mucosa, but an AOB region was not evident. These findings clarified that harbor seals do not have a VNO to detect some chemicals, but the corresponding region is a specialized secretory organ.

Although the functional significance of adult neurogenesis in hippocampal-dependent learning and memory has been well documented, the role of such neurogenesis in olfactory activity is rather obscure. To understand the significance of adult neurogenesis in olfactory functions, we genetically ablated newly born neurons by using tamoxifen-treated Nestin-CreERT²;neuron-specific enolase-diphtheria toxin fragment A (NSE-DTA) mice. In these mice, tamoxifen-inducible Cre recombinase allows the NSE (Eno2) gene to drive DTA expression in differentiating neurons, leading to the efficient ablation of newly born neurons in the forebrain. These mutant mice were capable of discriminating odors as competently as control mice. Strikingly, although control and mutant mice frequently showed freezing behaviors to a fox scent, a predator odor, mutant mice approached this odor when they were conditioned to associate the odor with a reward, whereas control mice did not approach the odor. Furthermore, although mutant males and females showed normal social recognition behaviors to other mice of a different sex, mutant males displayed deficits in male-male aggression and male sexual behaviors toward females, whereas mutant females displayed deficits in fertility and nurturing, indicating that sex-specific activities, which are known to depend on olfaction, are impaired. These results suggest that continuous neurogenesis is required for predator avoidance and sex-specific responses that are olfaction dependent and innately programmed.

The vomeronasal organ (VNO) is sensory organ located in the ventral region of the nasal cavity in rodents. The VNO develops from the olfactory placode during the secondary invagination of olfactory pit. The embryonic vomeronasal structure appears as a neurogenic area where migratory neuronal populations like endocrine gonadotropin-releasing hormone-1 (GnRH-1) neurons form. Even though embryonic vomeronasal structures are conserved across most vertebrate species, many species including humans do not have a functional VNO after birth. The vomeronasal epithelium (VNE) of rodents is composed of two major types of vomeronasal sensory neurons (VSNs): (1) VSNs distributed in the apical VNE regions that express vomeronasal type-1 receptors (V1Rs) and the G protein subunit Gαi2, and (2) VSNs in the basal territories of the VNE that express vomeronasal type-2 receptors (V2Rs) and the G subunit Gαo. Recent studies identified a third subclass of Gαi2 and Gαo VSNs that express the formyl peptide receptor family. VSNs expressing V1Rs or V2Rs send their axons to distinct regions of the accessory olfactory bulb (AOB). Together, VNO and AOB form the accessory olfactory system (AOS), an olfactory subsystem that coordinates the social and sexual behaviors of many vertebrate species. In this review, we summarize our current understanding of cellular and molecular mechanisms that underlie VNO development. We also discuss open questions for study, which we suggest will further enhance our understanding of VNO morphogenesis at embryonic and postnatal stages.