Protein pheromone expression levels predict and respond to the formation of social dominance networks

Communication signals are key regulators of social networks and are thought to be under selective pressure to honestly reflect social status, including dominance status. The odours of dominants and nondominants differentially influence behaviour, and identification of the specific pheromones associated with, and predictive of, dominance status is essential for understanding the mechanisms of network formation and maintenance. In mice, major urinary proteins (MUPs) are excreted in extraordinary large quantities and expression level has been hypothesized to provide an honest signal of dominance status. Here, we evaluate whether MUPs are associated with dominance in wild‐derived mice by analysing expression levels before, during and after competition for reproductive resources over 3 days. During competition, dominant males have 24% greater urinary MUP expression than nondominants. The MUP darcin, a pheromone that stimulates female attraction, is predictive of dominance status: dominant males have higher darcin expression before competition. Dominants also have a higher ratio of darcin to other MUPs before and during competition. These differences appear transient, because there are no differences in MUPs or darcin after competition. We also find MUP expression is affected by sire dominance status: socially naive sons of dominant males have lower MUP expression, but this apparent repression is released during competition. A requisite condition for the evolution of communication signals is honesty, and we provide novel insight into pheromones and social networks by showing that MUP and darcin expression is a reliable signal of dominance status, a primary determinant of male fitness in many species.     

Major urinary proteins, alpha(2U)-globulins and aphrodisin

The major urinary proteins (MUPs) are proteins secreted by the liver and filtered by the kidneys into the urine of adult male mice and rats, the MUPs of rats being also referred to as alpha(2U)-globulins. The MUP family also comprises closely related proteins excreted by exocrine glands of rodents, independently of their sex. The MUP family is an expression of a multi-gene family. There is complex hormonal and tissue-specific regulation of MUP gene expression. The multi-gene family and its outflow are characterized by a polymorphism which extends over species, strains, sexes, and individuals. There is evidence of evolutionary conservation of the genes and their outflow within the species and evidence of change between species. MUPs share the eight-stranded beta-barrel structure lining a hydrophobic pocket, common to lipocalins. There is also a high degree of structural conservation between mouse and rat MUPs. MUPs bind small natural odorant molecules in the hydrophobic pocket with medium affinity in the 10(4)-10(5) M(-1) range, and are excreted in the field, with bound odorants. The odorants are then released slowly in air giving a long lasting olfactory trace to the spot. MUPs seem to play complex roles in chemosensory signalling among rodents, functioning as odorant carriers as well as proteins that prime endocrine reactions in female conspecifics. Aphrodisin is a lipocalin, found in hamster vaginal discharge, which stimulates male copulatory behaviour. Aphrodisin does not seem to bind odorants and no polymorphism has been shown. Both MUPs and aphrodisin stimulate the vomeronasal organ of conspecifics.     

Male pheromones and their reception by females are co-adapted to affect mating success in two subspecies of brown rats

Pheromonal communication plays a key role in the sociosexual behavior of rodents. The coadaptation between pheromones and chemosensory systems has been well illustrated in insects but poorly investigated in rodents and other mammals. We aimed to investigate whether coadaptation between male pheromones and female reception might have occurred in brown rats Rattus norvegicus. We recently reported that major urinary protein (MUP) pheromones are associated with male mating success in a brown rat subspecies, R. n. humiliatus (Rnh). Here, we discovered that MUPs were less polymorphic and occurred at much lower concentrations in males of a parapatric subspecies, R. n. caraco (Rnc), than in Rnh males, and found no association between pheromones and paternity success. Moreover, the observation of Rnc males that experienced chronic dyadic encounters and established dominance–submission relationships revealed that the dominant males achieved greater mating success than the subordinate males, but their MUP levels did not differ by social status. These findings suggest that male mating success in Rnc rats is related to social rank rather than to pheromone levels and that low concentration of MUPs might not be a reliable signal for mate choice in Rnc rats, which is different from the findings obtained in Rnh rats. In addition, compared with Rnh females, Rnc females exhibited reduced expression of pheromone receptor genes, and a lower number of vomeronasal receptor neurons were activated by MUP pheromones, which imply that the female chemosensory reception of pheromones might be structurally and functionally coadapted with male pheromone signals in brown rats.     

Pheromonal communication in amphibians

Pheromonal communication is widespread in salamanders and newts and may also be important in some frogs and toads. Several amphibian pheromones have been behaviorally, biochemically and molecularly identified. These pheromones are typically peptides or proteins. Study of pheromone evolution in plethodontid salamanders has revealed that courtship pheromones have been subject to continual evolutionary change, perhaps as a result of co-evolution between the pheromonal ligand and its receptor. Pheromones are detected by the vomeronasal organ and main olfactory epithelium. Chemosensory neurons express vomeronasal receptors or olfactory receptors. Frogs have relatively large numbers of vomeronasal receptors that are transcribed in both the vomeronasal organ and the main olfactory epithelium. Salamander vomeronasal receptors apparently are restricted to the vomeronasal organ. To date, no chemosensory ligands have been matched to vomeronasal receptors or olfactory receptors so it is unknown whether particular receptor types are (1) specialized for detection of pheromones versus other chemosignals, or (2) specialized for detection of volatile, nonvolatile, or water-borne chemosignals. Despite progress in understanding amphibian pheromonal communication, only a small fraction of amphibian species have been examined. Study of additional species of amphibians will indicate which traits related to pheromonal communication are evolutionarily conserved and which traits have diverged over time.     

Mating Increases Neuronal Tyrosine Hydroxylase Expression and Selectively Gates Transmission of Male Chemosensory Information in Female Mice

Exposure to chemosensory signals from unfamiliar males can terminate pregnancy in recently mated female mice. The number of tyrosine hydroxylase-positive neurons in the main olfactory bulb has been found to increase following mating and has been implicated in preventing male-induced pregnancy block during the post-implantation period. In contrast, pre-implantation pregnancy block is mediated by the vomeronasal system, and is thought to be prevented by selective inhibition of the mate’s pregnancy blocking chemosignals, at the level of the accessory olfactory bulb. The objectives of this study were firstly to identify the level of the vomeronasal pathway at which selective inhibition of the mate’s pregnancy blocking chemosignals occurs. Secondly, to determine whether a post-mating increase in tyrosine hydroxylase-positive neurons is observed in the vomeronasal system, which could play a role in preventing pre-implantation pregnancy block. Immunohistochemical staining revealed that mating induced an increase in tyrosine-hydroxylase positive neurons in the arcuate hypothalamus of BALB/c females, and suppressed c-Fos expression in these neurons in response to mating male chemosignals. This selective suppression of c-Fos response to mating male chemosignals was not apparent at earlier levels of the pregnancy-blocking neural pathway in the accessory olfactory bulb or corticomedial amygdala. Immunohistochemical staining revealed an increase in the number of tyrosine hydroxylase-positive neurons in the accessory olfactory bulb of BALB/c female mice following mating. However, increased dopamine-mediated inhibition in the accessory olfactory bulb is unlikely to account for the prevention of pregnancy block to the mating male, as tyrosine hydroxylase expression did not increase in females of the C57BL/6 strain, which show normal mate recognition. These findings reveal an association of mating with increased dopaminergic modulation in the pregnancy block pathway and support the hypothesis that mate recognition prevents pregnancy block by suppressing the activation of arcuate dopamine release.     

Conditioned odor aversion induces social anxiety towards females in wild‐type and TrpC2 knockout male mice

Female‐emitted pheromonal inputs possess an intrinsic rewarding value for conspecific males, promoting approach and investigation of the potential mating partner. In mice these inputs are detected mainly by the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). We investigated the role of VNO‐mediated inputs in experience‐dependent plasticity of reproductive responses. We applied a sex‐specific conditioned odor aversion (COA) paradigm on adult, wild‐type (WT) male mice and on male mice impaired in VNO‐mediated signal transduction (TrpC2^?/?). We found that WT males, which underwent COA to female‐soiled bedding, lost their innate preference to female odors and presented lower motivation to approach a sexually receptive female. COA also abolished the testosterone surge normally seen following exposure to female odors. Moreover, the conditioned males displayed impairments in copulatory behaviors, which lasted for several weeks. Surprisingly, these males also exhibited phobic behaviors towards receptive females, including freezing and fleeing responses. In contrast, WT males which underwent COA specifically to male pheromones showed no change in olfactory preference and only a marginally significant elevation in intermale aggression. Finally, we show that TrpC2^?/? males were able to acquire aversion to female‐soiled bedding and presented similar behavioral alterations following COA in their responses to female cues. Our results demonstrate that the intrinsic rewarding value of female pheromones can be overridden through associative olfactory learning, which occurs independently of VNO inputs, probably through MOE signaling.     

Are MUPs a Toxic Waste Disposal System?

Male house mice produce large quantities of major urinary proteins (MUPs), which function to bind and transport volatile pheromones, though they may also function as scavengers that bind and excrete toxic compounds (‘toxic waste hypothesis’). In this study, we demonstrate the presence of an industrial chemical, 2,4-di-tert-butylphenol (DTBP), in the urine of wild-derived house mice (Mus musculus musculus). Addition of guanidine hydrochloride to male and female urine resulted in an increased release of DTBP. This increase was only observed in the high molecular weight fractions (HMWF; > 3 kDa) separated from male or female urine, suggesting that the increased release of DTBP was likely due to the denaturation of MUPs and the subsequent release of MUP-bound DTBP. Furthermore, when DTBP was added to a HMWF isolated from male urine, an increase in 2-sec-butyl-4,5-dihydrothiazole (SBT), the major ligand of MUPs and a male-specific pheromone, was observed, indicating that DTBP was bound to MUPs and displaced SBT. These results suggest that DTBP is a MUP ligand. Moreover, we found evidence for competitive ligand binding between DTBP and SBT, suggesting that males potentially face a tradeoff between eliminating toxic wastes versus transporting pheromones. Our findings support the hypothesis that MUPs bind and eliminate toxic wastes, which may provide the most important fitness benefits of excreting large quantities of these proteins.     

Evolutionary patterns of major urinary protein scent signals in house mice and relatives

Scent marks are important mediators of territorial behaviour and sexual selection, especially among mammals. The evolution of compounds used in scent marks has the potential to inform our understanding of signal evolution in relation to social and sexual selection. A major challenge in studies of chemical communication is that the link between semiochemical compounds and genetic changes is often unclear. The major urinary proteins (MUPs) of house mice provide information on sex, status and individual identity. Importantly, MUPs are a direct protein product of genes, providing a clear link between genotype and phenotype. Here, we examine the evolution of urinary protein signals among house mice and relatives by examining the sequences and patterns of mRNA expression of Mup genes related to urinary scent marks. MUP patterns have evolved among mouse species both by gene duplication and variation in expression. Notably, protein scent signals that are male specific in well‐studied inbred laboratory strains vary in sex‐specificity among species. Our data reveal that individual identity signals in MUPs evolved prior to 0.35 million years ago and have rapidly diversified through recombining a modest number of amino acid variants. Amino acid variants are much more common on the exterior of the protein where they could interact with vomeronasal receptors, suggesting that chemosensory perception may have played a major role in shaping MUP diversity. These data highlight diverse processes and pressures shaping scent signals, and suggest new avenues for using wild mice to probe the evolution of signals and signal processing.     

The nose knows who's who: chemosensory individuality and mate recognition in mice

Individual recognition is an important component of behaviors, such as mate choice and maternal bonding that are vital for reproductive success. This article highlights recent developments in our understanding of the chemosensory cues and the neural pathways involved in individuality discrimination in rodents. There appear to be several types of chemosensory signal of individuality that are influenced by the highly polymorphic families of major histocompatibility complex (MHC) proteins or major urinary proteins (MUPs). Both have the capability of binding small molecules and may influence the individual profile of these chemosignals in biological fluids such as urine, skin secretions, or saliva. Moreover, these proteins, or peptides associated with them, can be taken up into the vomeronasal organ (VNO) where they can potentially interact directly with the vomeronasal receptors. This is particularly interesting given the expression of major histocompatibility complex Ib proteins by the V2R class of vomeronasal receptor and the highly selective responses of accessory olfactory bulb (AOB) mitral cells to strain identity. These findings are consistent with the role of the vomeronasal system in mediating individual discrimination that allows mate recognition in the context of the pregnancy block effect. This is hypothesized to involve a selective increase in the inhibitory control of mitral cells in the accessory olfactory bulb at the first level of processing of the vomeronasal stimulus.     

Male pheromones initiate prolactin-induced neurogenesis and advance maternal behavior in female mice

Prolactin is required for rapid onset of maternal behavior after parturition, inducing adaptive changes in the maternal brain including enhanced neurogenesis in the subventricular zone during pregnancy. The resultant increase in olfactory interneurons may be required for altered processing of olfactory cues during the establishment of maternal behavior. Pheromones act through olfactory pathways to exert powerful effects on behavior in rodents and also affect prolactin secretion. Hence, this study aimed to investigate the effect of male pheromones on neurogenesis and maternal behavior in female mice. Virgin female mice were housed individually or in split-cages where they had pheromonal but not physical contact with a male. Maternal behavior was assessed in a foster pup retrieval paradigm. Some mice were injected with bromodeoxyuridine, and the labeled cells visualized using immunohistochemistry. The data show that exposure to male pheromones, for a duration equivalent to a murine pregnancy, advanced maternal behavior in both virgin and postpartum female mice. The pheromone action was dependent on prolactin and ovarian steroids, and was associated with increased cell proliferation in the subventricular zone and subsequent increases in new neurons in the olfactory bulb. Moreover, the effect of pheromones on both cell proliferation and maternal behavior could be induced solely through administration of exogenous prolactin to mimic the pheromone-induced changes in prolactin secretion. The data suggest that male pheromones induce a prolactin-mediated increase in neurogenesis in female mice, resulting in advanced maternal behavior.     

Something in the air? New insights into mammalian pheromones

Olfaction is the dominant sensory modality for most animals and chemosensory communication is particularly well developed in many mammals. Our understanding of this form of communication has grown rapidly over the last ten years since the identification of the first olfactory receptor genes. The subsequent cloning of genes for rodent vomeronasal receptors, which are important in pheromone detection, has revealed an unexpected diversity of around 250 receptors belonging to two structurally different classes. This review will focus on the chemical nature of mammalian pheromones and the complementary roles of the main olfactory system and vomeronasal system in mediating pheromonal responses. Recent studies using genetically modified mice and electrophysiological recordings have highlighted the complexities of chemosensory communication via the vomeronasal system and the role of this system in handling information about sex and genetic identity. Although the vomeronasal organ is often regarded as only a pheromone detector, evidence is emerging that suggests it might respond to a much broader variety of chemosignals.     

Protein-bound male urinary pheromones: differential responses according to age and gender

The attractive properties of male urinary pheromones were tested on adult or prepubertal male and female mice. An androgen-dependent protein is present in adult male urine (major urinary protein, MUP) which has been suggested to be a pheromone-binding protein. We tested the pheromonal properties of the protein-bound volatiles in a test of attractiveness. These molecules, that co-purify with MUP, attract females and repel adult males. In prepubertal animals, females are repelled and males are attracted by the same stimuli. These results are similar to those obtained by others with adult male whole urine. Therefore MUP binds molecules with a pheromonal activity, and these molecules are sufficient to act as male signals.      

Trpc2 gene impacts on maternal aggression, accessory olfactory bulb anatomy and brain activity

The Trpc2 gene codes for an ion channel found in the vomeronasal organ (VNO). Studies using the Trpc 2^−/− (KO) mouse have exploited the gene's role in signal transduction to explore the VNO's role in pheromonally mediated behaviors. To date, no study has evaluated the impact of the Trpc2 gene on activity within the brain. In this study, we examine the gene's effect on brain regions governing maternal aggression. We intruder-tested lactating dams and then quantified Fos immunoreactivity (Fos-IR) in the vomeronasal amygdala, hypothalamus, olfactory regions and accessory olfactory bulb (AOB). Our data confirm previous reports that loss of the Trpc2 gene severely diminishes maternal aggression. We also show that deletion of the gene results in differential hypotrophy of the glomerular layer (GlA) of the AOB, with the anterior portion the GlA resembling that of wild-type mice, and the posterior portion reduced or absent. This anatomy is suggestive of residual functioning in the apical VNO of these animals. Our Fos study describes an impact of the deletion on a network of 21 brain regions involved in emotion, aggression and olfaction, suggesting that signals from the VNO mediate activity throughout the brain. Home-cage observations of KO dams show specific deficits in nest-building, suggesting a role for pup pheromones in inducing and maintaining pup-directed maternal behaviors as well as maternal aggression.     

Effects of resource distribution on activity and territory defence in house mice, Mus domesticus

How much an animal invests in defending a territory depends, in part, on the quality, quantity and distribution of resources, but do animals target their investment in defence within the territory according to the location of different resources? We examined whether wild-caught male and female house mice increased aggression towards intruders of the same or opposite sex when in areas containing their food/water or nest site. Pairs of resident mice were established in enclosures consisting of two areas. In split enclosures, food and water were in one area and a nest site in the other, while in clumped enclosures all resources were in one area with no resources in the other. Residents of both sexes were quicker to attack intruders, and were more aggressive, in areas containing resources than in an area containing no resources. There was no difference in aggression between areas containing food/water, a nest site or both. The effect of resources on territorial defence was due largely to changes in aggression against intruders of the opposite sex. Residents, especially males, attacked intruders of their own sex more than those of the opposite sex. This bias was much stronger when no resources were present, owing to low aggression against opposite-sex intruders in the absence of resources. There were no differences in intruder aggression, and the relative size of the intruder (heavier or lighter than the resident) had no effect on resident aggression. Residents also spent less time out of their nest in clumped enclosures owing to low activity in the nonresource area.     

Identification and characterization of functional genes encoding the mouse major urinary proteins.

Mouse Ltk- cells were stably transfected with cloned genes encoding the mouse major urinary proteins (MUPs). C57BL/6J MUP genomic clones encoding MUP 2 (BL6-25 and BL6-51), MUP 3 (BL6-11 and BL6-3), and MUP 4 (BL6-42) have been identified. In C57BL/6J mice, MUP 2 and MUP 4 are known to be synthesized in male, but not female, liver, and MUP 3 is known to be synthesized in both male and female liver and mammary gland. A BALB/c genomic clone (BJ-31) was shown to encode a MUP that is slightly more basic than MUP 2 and was previously shown to be synthesized in both male and female liver of BALB/c but not C57BL/6 mice. Comigration on two-dimensional polyacrylamide gels of the MUPs encoded by the transfecting gene provides a basis for tentative identification of the tissue specificity and mode of regulation of each gene. DNA sequence analysis of the 5' flanking region indicates that the different MUP genes are highly homologous (0.20 to 2.40% divergence) within the 879 base pairs analyzed. The most prominent differences in sequence occur within an A-rich region just 5' of the TATA box. This region (from -47 to -93) contains primarily A or C(A)N nucleotides and varies from 15 to 46 nucleotides in length in the different clones.     

The Structure,Stability and Pheromone Binding of the Male Mouse Protein Sex Pheromone Darcin

Mouse urine contains highly polymorphic major urinary proteins that have multiple functions in scent communication through their abilities to bind, transport and release hydrophobic volatile pheromones. The mouse genome encodes for about 20 of these proteins and are classified, based on amino acid sequence similarity and tissue expression patterns, as either central or peripheral major urinary proteins. Darcin is a male specific peripheral major urinary protein and is distinctive in its role in inherent female attraction. A comparison of the structure and biophysical properties of darcin with MUP11, which belongs to the central class, highlights similarity in the overall structure between the two proteins. The thermodynamic stability, however, differs between the two proteins, with darcin being much more stable. Furthermore, the affinity of a small pheromone mimetic is higher for darcin, although darcin is more discriminatory, being unable to bind bulkier ligands. These attributes are due to the hydrophobic ligand binding cavity of darcin being smaller, caused by the presence of larger amino acid side chains. Thus, the physical and chemical characteristics of the binding cavity, together with its extreme stability, are consistent with darcin being able to exert its function after release into the environment.     

Pre-exposure to female chemosignals or intracerebral GnRH restores mating behavior in naive male hamsters with vomeronasal organ lesions

Chemosensory input is essential for mating in male hamsters and the vomeronasal organ is critical to mating in naive males. In studies to investigate the convergence of vomeronasal chemosensory input and the neurohormone gonadotrophin releasing hormone (GnRH), we have unexpectedly found that pre-exposure to pheromone-containing chemosignals from female hamsters will also eliminate mating deficits normally seen in naive male hamsters with vomeronasal organs removed (VNX). In the present studies, naive-intact and naive-VNX male hamsters were given intracerebroventricular injections of GnRH or saline and exposed to female pheromones found in hamster vaginal fluid (HVF) or to water 40 min prior to a 5 min mating test. VNX males given saline injections and exposed to water had severe mating deficits, but VNX males given saline injections and exposed to HVF mated normally. As shown previously, males given GnRH injections and exposed to water also mated normally. HVF exposure prior to a mating test apparently acted to compensate for the lack of vomeronasal input in these males.     

Maternal aggression as a deterrent to infanticide in Peromyscus leucopus and P. maniculatus

Adult male and female white-footed mice (Peromyscus leucopus) and deermice (P. maniculatus) from sympatric populations commit infanticide on neonates of either species. A laboratory experiment was conducted to determine whether aggression in maternal females could effectively deter infanticidal intruders. Females of both species exhibited post-partum aggression and dominated intruders of either sex or species in 83 of 88 trials. In the absence of the mother, neonates were attacked by intruders in 82 out of 84 trials. Maternal females were considerably more aggressive than anoestrous females. The implications for female territorially as a mechanism to prevent infanticide are discussed.     

Cross-Fostering of Male Mice Subtly Affects Female Olfactory Preferences

The maternal environment has been shown to influence female olfactory preferences through early chemosensory experience. However, little is known about the influence of the maternal environment on chemosignals. In this study, we used two inbred mouse strains, C57BL/6 (C57) and BALB/c (BALB), and explored whether adoption could alter male chemosignals and thus influence female olfactory preferences. In Experiment 1, C57 pups were placed with BALB dams. Adult BALB females then served as the subjects in binary choice tests between paired male urine odours (BALB vs. C57, BALB vs. adopted C57 and C57 vs. adopted C57). In Experiment 2, BALB pups were placed with C57 dams, and C57 females served as the subjects in binary choice tests between paired male urine odours (C57 vs. BALB, C57 vs. adopted BALB, and BALB vs. adopted BALB). In both experiments, we found that females preferred the urine of males from different genetic backgrounds, suggesting that female olfactory preferences may be driven by genetic compatibility. Cross-fostering had subtle effects on female olfactory preferences. Although the females showed no preference between the urine odours of adopted and non-adopted males of the other strain, the BALB females preferred the urine odour of BALB males to that of adopted C57 males, whereas the C57 females showed no preference between the urine odour of C57 and adopted BALB males. Using gas chromatography-mass spectrometry (GC-MS) and stepwise discriminant analysis, we found that the ratios of volatile chemicals from urine and preputial gland secretions were altered in the fostered male mice; these changes may have resulted in the behavioural changes observed in the females. Overall, the results suggest that female mice prefer urine odours from males with different genetic backgrounds; this preference may be driven by genetic compatibility. The early maternal environment influences the chemosignals of males and thus may influence the olfactory preferences of females. Our study provides additional evidence in support of genotype-dependent maternal influences on phenotypic variability in adulthood.     

Mammalian social odours: attraction and individual recognition

Mammalian social systems rely on signals passed between individuals conveying information including sex, reproductive status, individual identity, ownership, competitive ability and health status. Many of these signals take the form of complex mixtures of molecules sensed by chemosensory systems and have important influences on a variety of behaviours that are vital for reproductive success, such as parent-offspring attachment, mate choice and territorial marking. This article aims to review the nature of these chemosensory cues and the neural pathways mediating their physiological and behavioural effects. Despite the complexities of mammalian societies, there are instances where single molecules can act as classical pheromones attracting interest and approach behaviour. Chemosignals with relatively high volatility can be used to signal at a distance and are sensed by the main olfactory system. Most mammals also possess a vomeronasal system, which is specialized to detect relatively non-volatile chemosensory cues following direct contact. Single attractant molecules are sensed by highly specific receptors using a labelled line pathway. These act alongside more complex mixtures of signals that are required to signal individual identity. There are multiple sources of such individuality chemosignals, based on the highly polymorphic genes of the major histocompatibility complex (MHC) or lipocalins such as the mouse major urinary proteins. The individual profile of volatile components that make up an individual odour signature can be sensed by the main olfactory system, as the pattern of activity across an array of broadly tuned receptor types. In addition, the vomeronasal system can respond highly selectively to non-volatile peptide ligands associated with the MHC, acting at the V2r class of vomeronasal receptor. The ability to recognize individuals or their genetic relatedness plays an important role in mammalian social behaviour. Thus robust systems for olfactory learning and recognition of chemosensory individuality have evolved, often associated with major life events, such as mating, parturition or neonatal development. These forms of learning share common features, such as increased noradrenaline evoked by somatosensory stimulation, which results in neural changes at the level of the olfactory bulb. In the main olfactory bulb, these changes are likely to refine the pattern of activity in response to the learned odour, enhancing its discrimination from those of similar odours. In the accessory olfactory bulb, memory formation is hypothesized to involve a selective inhibition, which disrupts the transmission of the learned chemosignal from the mating male. Information from the main olfactory and vomeronasal systems is integrated at the level of the corticomedial amygdala, which forms the most important pathway by which social odours mediate their behavioural and physiological effects. Recent evidence suggests that this region may also play an important role in the learning and recognition of social chemosignals.