Impaired discrimination of and aversion to parasitized male odors by female oxytocin knockout mice

A major cost of social behavior is the increased risk of exposure to parasites, with animals utilizing social information to recognize and avoid infected conspecifics. In mice, females can discriminate between infected and uninfected males on the basis of social cues, displaying aversive responses to the odors of infected males. In the present study, using female mice whose gene for oxytocin (OT) has been selectively deleted (OT knockout mice (OTKO)), we show that at least one normal allele for OT is required for the mediation of the recognition and avoidance of parasitized males. Female wild type (OTWT) and heterozygous (OTHZ) mice distinguished between the odors of individual males infected with the louse, Polyplax serrata , and uninfected males while the KO mice did not. Exposure to the odors of infected males induced analgesia in OTWT and OTHZ females, with OTKO females displaying attenuated analgesia. OTWT and OTHZ females, but not the OTKO females, also distinguished between the odors of novel and familiar infected males and modulated their analgesic responses on the basis of prior familiarity. In an odor choice test, OTWT and OTHZ females displayed a marked initial choice for the odors of uninfected males, whereas the OTKO females showed no consistent choice. This impairment was specific to the odors of infected males. OTKO females displayed normal analgesic responses to another aversive social odor, that of a stressed male, and an aversive non-social odor, that of a cat. The OTKOs had normal non-social olfactory memory, but were impaired in their social odor memory. These findings indicate that a normal OT gene comprises an essential part of the central recognition mechanism whereby females can both reduce the transmission of parasites to themselves and select for parasite-free males.     

Oxytocin and estrogen receptor alpha and beta knockout mice provide discriminably different odor cues in behavioral assays

Social behavior involves both the recognition and production of social cues. Mice with selective deletion (knockout) of either the gene for oxytocin (OT) or genes for the estrogen receptor (ER) -α or -β display impaired social recognition. In this study we demonstrate that these gene knockout mice also provide discriminably different social stimuli in behavioral assays. In an odor choice test, which is a measure of social interest and discrimination, outbred female Swiss-Webster mice discriminated the urine odors of male knockouts (KO: OTKO, αERKO, βERKO) from the odors of their wildtype littermates (WT: OTWT, αERWT, βERWT). Females showed marked initial choices of the urine odors of OTWT and βERWT males over those of OTKO and βERKO males, and αERKO males over αERWT males. The odors of OTKO and βERKO males also induced aversive, analgesic responses, with the odors of WTs having no significant effects. Odors of both the αERWT and αERKO males induced aversive, analgesic responses, with the odors of the WT inducing significantly greater analgesia. The odors of restraint stressed WT and KO males also elicited analgesia with, again, females displaying significantly greater responses to the odors of stressed OTKO and βERKO males than their WTs, and significantly lower analgesia to the odors of stressed αERKO than αERWT males. These findings show that the KO mice are discriminated from their WTs on the basis of odor and that the various KOs differ in the relative attractiveness/aversiveness of their odors. Therefore, in behavioral assays one causal route by which gene inactivation alters the social behavior of knockout mice may be mediated through the partners' modified responses to their odors.     

Social neuroscience of disgust

Disgust can be thought of as an affective system that has evolved to detect signs of pathogens, parasite and toxins as well as to stimulate behaviors that reduce the risk of their acquisition. Disgust incorporates social cognitive mechanisms to regulate exposure to and, or anticipate and avoid exposure to pathogens and toxins. Social cognition entails the acquisition of social information about others (ie, social recognition) and from others (ie, social learning). This involves recognizing and assessing other individuals and the pathogen/parasite/contamination/toxin threat they pose and deciding about when and how to interact with and, or avoid them. Social cognition provides a frame‐work for examining the expression of disgust and the associated neurobiological mechanisms. Here, we briefly consider the relations between social cognition and pathogen/parasite/toxin avoidance behaviors. We briefly discuss aspects of: (1) the odor mediated social recognition of actual and potentially infected individuals and the impact of parasite/pathogen threat on disgust mate and social partner choice; (2) the roles of “out‐groups” (strangers, unfamiliar individuals) and “in‐groups” (familiar individuals) in the expression of disgust and pathogen avoidance behaviors; (3) individual and social learning of disgust and empathy for disgust; (4) toxin elicited disgust and anticipatory disgust; (5) the neurobiological mechanisms, and in particular the roles of the nonapeptide, oxytocin and estrogenic mechanism associated with social cognition and the expression of disgust. These findings on the social neuroscience of disgust have a direct bearing on our understanding of the roles of disgust in shaping human and nonhuman social behavior.     

Genes, odours and the recognition of parasitized individuals by rodents

Social recognition, whereby animals identify and recognize other individual conspecifics, is a crucial prerequisite for a wide range of social behaviours. There are relationships among social odours (chemical signals), parasite recognition and avoidance that are associated with hormonal, neural and genomic mechanisms in rodents. Rodents use social odours to: (i) distinguish between infected and uninfected individuals; (ii) recognize specific infected individuals; and (iii) avoid and display aversive responses to infected individuals. There are genomic correlates of this parasite recognition and avoidance in which genes expressing the neuropeptide oxytocin have roles. In this article, we provide a framework ("micronet") by which the genetic, hormonal and neural interactions associated with social behaviours and recognition and avoidance of parasitized individuals can be explored.     

Aversive Responses of Female Mice to the Odors of Parasitized Males: Neuromodulatory Mechanisms and Implications for Mate Choice

The detection and avoidance of parasitized conspecifics is proposed to have important consequences for the behavior of animals, especially as related to mate choice. A reduction in pain sensitivity (i.e. analgesia) is a major correlate of exposure to real or potential danger and threatening stimuli, facilitating the expression of various active (e.g. fleeing) and passive (e.g. immobilization) defense responses. The present study examined pain sensitivity (latency of a foot-lifting response to 50 ° C thermal surface) of female mice, Mus musculus, that were exposed to the urine and other odor secretions of male mice subclinically infected with the naturally occurring, enteric, sporozoan parasite, Eimeria vermiformis. A 30-min exposure to the odors of a parasitized male induced an analgesia in the female mice that was found to be mediated by the increased activity of endogenous opioid peptide systems. A brief 1-min exposure to the male odors induced a shorter duration and lower amplitude analgesia of a non-opioid (serotonergic) nature. Maximum analgesic responses were induced by the odors of pre-infective [5 days post-infection (PI)] and infective (day 10 PI) males, with significantly lower responses elicited by the odors of post-infective (day 17 PI) male mice. Exposure to the odors of unparasitized males had no significant effects on the pain sensitivity of female mice. These results indicate that female mice can distinguish between the odors of parasitized and non-parasitized male mice, and find the odors of parasitized males threatening and/or stressful. These odor-induced analgesic responses and their neurohormonal correlates may be part of an adaptive preparatory defense mechanism that facilitates the detection and avoidance of parasitized males by female mice and contributes to female mate choice.     

Species and Colony Components in the Recognition Odor of Young Social Wasps: Their Expression and Learning (Polistes biglumis and P. atrimandibularis; Hymenoptera: Vespidae)

In Polistes, nestmate recognition relies on the learning of recognition cues from the nest. When wasps recognize nestmates, they match the template learned with the odor of the encountered wasp. The social wasp Polistes biglumis use the homogeneous odor of their colony to recognize nestmates. When these colonies become host colonies of the social parasite P. atrimandibularis, colony odor is no longer homogeneous, as the parasite offspring have an odor that differs from that of their hosts. In trying to understand how the mechanism of nestmate recognition works in parasitized colonies and why parasite offspring are accepted by hosts, we tested the responses of resident Polistes biglumis wasps from parasitized and unparasitized colonies to newly emerged parasites and to nestmate and non-nestmate conspecifics. The experiments indicate that immediately upon eclosion both young parasites and young hosts lack a colony odor and that colony odor can be soon acquired from the accepting colony. In addition, while residents of nonparasitized colonies recognize only the odor of their species, resident hosts of parasitized colonies have learned a template that fits the odors of two species.     

Oxytocin (OT) and arginine-vasopressin (AVP) act on OT receptors and not AVP V1a receptors to enhance social recognition in adult Syrian hamsters (Mesocricetus auratus)

Social recognition is a fundamental requirement for all forms of social relationships. A majority of studies investigating the neural mechanisms underlying social recognition in rodents have investigated relatively neutral social stimuli such as juveniles or ovariectomized females over short time intervals (e.g., 2 h). The present study developed a new testing model to study social recognition among adult males using a potent social stimulus. Flank gland odors are used extensively in social communication in Syrian hamsters and convey important information such as dominance status. We found that the recognition of flank gland odors after a 3 min exposure lasted for at least 24 h, substantially longer than the recognition of other social cues in rats and mice. Intracerebroventricular injections of OT and AVP prolonged the recognition of flank gland odor for up to 48 h. Selective OTR but not V1aR agonists, mimicked these enhancing effects of OT and AVP. Similarly, selective OTR but not V1aR antagonists blocked recognition of the odors after 20 min. In contrast, the recognition of non-social stimuli was not blocked by either the OTR or the V1aR antagonists. Our findings suggest both OT and AVP enhance social recognition via acting on OTRs and not V1aRs and that the recognition enhancing effects of OT and AVP are limited to social stimuli.     

Effects of blood parasites on sexual and natural selection in the pied flycather

The occurrence of the blood parasites Haemoproteus and Trypanosoma in the pied flycatcher, Ficedula hypoleuca , was examined to test current hypotheses that parasites reduce the expression of secondary sexual traits, mating success, breeding success, and survival of infected individuals. The results showed that there was no significant relationship between male plumage brightness and Trypanosoma infection, but males infected with Haemoproteus tended to be brighter than uninfected males, partly because first-year males were less often infected than older males. Polygynous males did not have fewer parasites than monogamous males. Females did not choose uninfected males among those they had sampled. Clutch size and laying date were not related to female infection status, and the number and quality of nestlings was not related to parasite infections of either male or female parent. The ability of males to provide parental care was not related to their infection status. The return rate from one breeding season to the next of infected males was not lower than that of uninfected males. The lack of correlations between parasites and male plumage colour and female mate choice apparently do not support the Hamilton-Zuk hypothesis of sexual selection. However, the absence of demonstration of any negative effects of parasites suggests that infection status may not be a direct measure of parasite resistance, or the degree to which the host suffers. Instead, the results support the alternative view that infected individuals have demonstrated their ability to survive and to cope with the parasites, while uninfected individuals are probably not yet tested for their resistance. This points to problems in using parasite prevalences and distributions, at least of some protozoan blood parasites, for tests of Hamilton-Zuk hypothesis, even though this was done in the first test by Hamilton and Zuk and by many later researchers     

Avian Influenza Infection Alters Fecal Odor in Mallards

Changes in body odor are known to be a consequence of many diseases. Much of the published work on disease-related and body odor changes has involved parasites and certain cancers. Much less studied have been viral diseases, possibly due to an absence of good animal model systems. Here we studied possible alteration of fecal odors in animals infected with avian influenza viruses (AIV). In a behavioral study, inbred C57BL/6 mice were trained in a standard Y-maze to discriminate odors emanating from feces collected from mallard ducks (Anas platyrhynchos) infected with low-pathogenic avian influenza virus compared to fecal odors from non-infected controls. Mice could discriminate odors from non-infected compared to infected individual ducks on the basis of fecal odors when feces from post-infection periods were paired with feces from pre-infection periods. Prompted by this indication of odor change, fecal samples were subjected to dynamic headspace and solvent extraction analyses employing gas chromatography/mass spectrometry to identify chemical markers indicative of AIV infection. Chemical analyses indicated that AIV infection was associated with a marked increase of acetoin (3-hydroxy-2-butanone) in feces. These experiments demonstrate that information regarding viral infection exists via volatile metabolites present in feces. Further, they suggest that odor changes following virus infection could play a role in regulating behavior of conspecifics exposed to infected individuals.     

Neonatal paternal deprivation impairs social recognition and alters levels of oxytocin and estrogen receptor α mRNA expression in the MeA and NAcc,and serum oxytocin in mandarin voles

Paternal care is necessary for the healthy development of social behavior in monogamous rodents and social recognition underpins social behavior in these animals. The effects of paternal care on the development of social recognition and underlying neuroendocrine mechanisms, especially the involvement of oxytocin and estrogen pathways, remain poorly understood. We investigated the effects of paternal deprivation (PD: father was removed from neonatal pups and mother alone raised the offspring) on social recognition in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the development of social recognition in female and male offspring according to a habituation–dishabituation paradigm. Paternal deprivation resulted in increased inactivity and reduced investigation during new encounters with other animals. Paternal deprivation reduced oxytocin receptor (OTR) and estrogen receptor α (ERα) mRNA expression in the medial amygdala and nucleus accumbens. Paternal deprivation reduced serum oxytocin (OT) concentration in females, but had no effect on males. Our results provide substantial evidence that paternal deprivation inhibits the development of social recognition in female and male mandarin voles and alters social behavior later in life. This is possibly the result of altered expression of central OTR and ERα and serum OT levels caused by paternal deprivation.     

The effects of Trichinella infection on intersexual interactions between mice

Parasitic infection may influence mating behaviour in at least two ways: (1) by creating a selection pressure for mate choice based on apparent resistance to infection and (2) by reducing the likelihood of an infected individual mating through induced changes in its physiology or behaviour. These two possibilities were tested using a nematode infection in laboratory mice. Female CFLP mice were infected with larvae of the aphasmid nematode Trichinella spiralis and allowed to interact with uninfected males which were either experienced or inexperienced in term of having previously copulated. Both the responses of males towards infected and uninfected females and the responses of females towards males were recorded. Overall, males were significantly less likely to mount, copulate and show other behaviours related to copulation with infected females. When experienced and inexperienced males were considered separately, experienced males showed significantly more investigatory activity towards infected females, but infection did not appear to affect responses by inexperienced males. Infected females were more likely to avoid or respond aggressively to attempts to mount by males and the latency to the first attempt to mount correlated positively with the frequency of avoidance/aggression towards approaching males. The results suggest that infection in females influences intersexual interactions by inducing a disinclination to accept mounts and copulate. The functional implications for parasite transmission are considered.     

MHC VARIATION IS RELATED TO A SEXUALLY SELECTED ORNAMENT,SURVIVAL, AND PARASITE RESISTANCE IN COMMON YELLOWTHROATS

Hamilton and Zuk proposed that females choose mates based on ornaments whose expression is dependent on their genetically based resistance to parasites. The major histocompatibility complex (MHC) plays an important role in pathogen recognition and is a good candidate for testing the relationships between immune genes and both ornament expression and parasite resistance. We tested the hypothesis that female common yellowthroats prefer to mate with more ornamented males, because it is a signal of their MHC‐based resistance to parasites and likelihood of survival. In this species, females prefer males that have larger black facial masks as extrapair mates. Using pyrosequencing, we found that mask size was positively related to the number of different MHC class II alleles, as predicted if greater variation at the MHC allows for the recognition of a greater variety of pathogens. Furthermore, males with more MHC class II alleles had greater apparent survival, and resistance to malaria infection was associated with the presence of a particular MHC class II allele. Thus, extrapair mating may provide female warblers with immunity genes that are related to parasite resistance, survival, and the expression of a male ornament, consistent with good genes models of sexual selection.     

Involvement of estrogen receptor alpha, beta and oxytocin in social discrimination: A detailed behavioral analysis with knockout female mice

Social recognition, processing, and retaining information about conspecific individuals is crucial for the development of normal social relationships. The neuropeptide oxytocin (OT) is necessary for social recognition in male and female mice, with its effects being modulated by estrogens in females. In previous studies, mice whose genes for the estrogen receptor-alpha (alpha-ERKO) and estrogen receptor-beta (beta-ERKO) as well as OTKO were knocked out failed to habituate to a repeatedly presented conspecific and to dishabituate when the familiar mouse is replaced by a novel animal (Choleris et al. 2003, Proc Natl Acad Sci USA 100, 6192-6197). However, a binary social discrimination assay, where animals are given a simultaneous choice between a familiar and a previously unknown individual, offers a more direct test of social recognition. Here, we used alpha-ERKO, beta-ERKO, and OTKO female mice in the binary social discrimination paradigm. Differently from their wild-type controls, when given a choice, the KO mice showed either reduced (beta-ERKO) or completely impaired (OTKO and alpha-ERKO) social discrimination. Detailed behavioral analyses indicate that all of the KO mice have reduced anxiety-related stretched approaches to the social stimulus with no overall impairment in horizontal and vertical activity, non-social investigation, and various other behaviors such as, self-grooming, digging, and inactivity. Therefore, the OT, ER-alpha, and ER-beta genes are necessary, to different degrees, for social discrimination and, thus, for the modulation of social behavior (e.g. aggression, affiliation).     

四川短尾鼩尿液气味在社会等级识别中的作用

本文在中立竞技场中通过两两互作确定四川短尾鼩(Anourosorex squamipes)同性个体间的社会等级,并在此基础上利用其尿液,研究不同社会等级个体的自我或非自我识别能力及模式、尿液气味的行为响应机制,以及社会等级识别能力。结果表明:(1)四川短尾鼩优势个体表现攻击行为较多,从属个体防御行为较多,优势个体的标记行为显著高于从属个体;攻击行为表现为同等级雄性高于同等级雌性,且雌性间的攻击强度低于雄性;(2)从属个体和优势个体分别对自身尿液气味和非自身尿液气味存在明显偏好差异;不同性别、等级个体自我识别模式差异不明显,不同社会等级个体对于自身识别模式和非自身尿液的行为反应模式均不同。不同社会等级个体具有自我识别能力且能力不同;(3)四川短尾鼩能够识别不同社会等级个体的尿液气味,雌性对雄性尿液更感兴趣,雄性对优势雄性尿液选择回避;雄性对其他个体的访问时间与嗅舔频次均显著高于雌性,雌雄个体在识别不同社会等级的尿液气味时存在性二型。     

Parasites reduce attractiveness and reproductive success in male grain beetles

Sexual characters may reveal the quality of a potential mate, including the mate's level of infection with parasites. Females that prefer males with low levels of infection or no infection may benefit in several ways. Direct benefits may include avoidance of infection, acquistition of larger nuptial gifts or enhancement in fecundity due to differences in male fertility. Females may also benefit indirectly by producing offspring that are more resistant to infections. We measured female preference for odours produced by male grain beetles, Tenebrio molitor, that were either infected by a tapeworm, Hymenolepis diminuta, or uninfected. This parasite is not transmitted directly between conspecifics. Females were attracted to odours of all males, but they were less attracted to those from parasitized males. To the contrary, females were preferentially attracted to infected females. Males did not show any biased attraction to odours from infected and uninfected male beetles. Females that mated with highly infected males produced fewer offspring than females mated to uninfected males, indicating parasitic infection inflicts multiple costs to males. These results are consistent with models of parasite-mediated sexual selection. Copyright 2000 The Association for the Study of Animal Behaviour.     

Social wasp parasites affect the nestmate recognition abilities of their hosts (<Emphasis Type="Italic">Polistes atrimandibularis</Emphasis> and <Emphasis Type="Italic">P. biglumis</Emphasis>, Hymenoptera,Vespidae)

Summary. Queens of the parasitic social wasp, Polistes atrimandibularis, temporarily mimic the odor of their host species, Polistes biglumis, but their offspring have parasite-specific odors. As a consequence, in parasitized colonies individuals with different odors co-inhabit the colony and host workers, who are responsible for colony defense, accept wasps with different odors. In order to verify whether this particular condition causes a change in recognition abilities of hosts, we tested nestmate/non-nestmate discrimination in field colonies invaded by social parasites (and in non-parasitized colonies as controls). Results show that parasitized colonies distinguish between nestmates and non-nestmates, distinguish their parasite queen from those that usurped alien colonies, and accept their parasite's non-mimetic offspring but make more recognition errors than non-parasitized colonies. The optimal acceptance threshold model predicts that when the frequency of encountering non-kin increases, residents become less permissive towards intruders. However, my data show that parasitized colonies are more permissive towards non-nestmates with respect to non-parasitized colonies but they are also more aggressive towards nestmates, suggesting that host workers' learning abilities are impaired.     

Neuroendocrine basis of social recognition

Studies conducted in the past two years have yielded several new insights about neuroendocrine regulation of social recognition. The social recognition deficits seen in oxytocin knockout mice have now been demonstrated in both males and females, as well as in female estrogen receptor knockout mice. The male vasopressin V1A receptor knockout mouse (but not V1B) has a profound social recognition deficit. Preliminary evidence suggests that female V1B receptor knockout mice could also have social memory deficits. Several lines of evidence have emerged that indicate that neuropeptide regulation is significantly modulated by gonadal and corticosteroid activation.     

成年布氏田鼠对个体气味信号的识别与记忆

将配对饲养的成年雌雄布氏田鼠分离, 通过分开单独饲养12 h , 1 d、2 d、3 d、5 d 和7 d 后雌、雄鼠对原配偶异性和陌生异性气味信号的选择实验, 探讨布氏田鼠对气味信号的识别和记忆。实验表明: 在分离12 h 和1 d 后, 雄鼠对陌生雌性气味的选择和探究行为显著多于对熟悉雌鼠气味, 而雌鼠对两种气味并未表现显著的探究差异; 布氏田鼠对气味信号的记忆维持的强度和时间随个体不同而产生差异, 雄鼠在分离后12 h、1d、2 d 中对陌生雌鼠气味均表现出差异明显的探究行为, 而后, 各项探究行为的差异均不明显。雌鼠探究行为变化比较缓慢。据此推测雄鼠对气味的记忆维持在2 d 左右。     

Genetic loss of diazepam binding inhibitor in mice impairs social interest

Neuropsychiatric disorders in which reduced social interest is a common symptom, such as autism, depression, and anxiety, are frequently associated with genetic mutations affecting γ‐aminobutyric acid (GABA)ergic transmission. Benzodiazepine treatment, acting via GABA type‐A receptors, improves social interaction in male mouse models with autism‐like features. The protein diazepam binding inhibitor (DBI) can act as an endogenous benzodiazepine, but a role for DBI in social behavior has not been described. Here, we investigated the role of DBI in the social interest and recognition behavior of mice. The responses of DBI wild‐type and knockout male and female mice to ovariectomized female wild‐type mice (a neutral social stimulus) were evaluated in a habituation/dishabituation task. Both male and female knockout mice exhibited reduced social interest, and DBI knockout mice lacked the sex difference in social interest levels observed in wild‐type mice, in which males showed higher social interest levels than females. The ability to discriminate between familiar and novel stimulus mice (social recognition) was not impaired in DBI‐deficient mice of either sex. DBI knockouts could learn a rotarod motor task, and could discriminate between social and nonsocial odors. Both sexes of DBI knockout mice showed increased repetitive grooming behavior, but not in a manner that would account for the decrease in social investigation time. Genetic loss of DBI did not alter seminal vesicle weight, indicating that the social interest phenotype of males lacking DBI is not due to reduced circulating testosterone. Together, these studies show a novel role of DBI in driving social interest and motivation.     

Parasite infection has little effect on sexual signals and reproductive behaviour in strawberry poison frogs

Acoustic and visual signals like mating calls or colour patterns, which are involved in courtship displays, can be affected by the health status of an individual. For example, infection with parasites can result in sexual signals that are less intense or conspicuous than in healthy individuals; thus it is generally assumed that sexual signals indicate the quality of the holder. We use strawberry poison frogs from Costa Rica to find out (1) whether there is variation in the parasite load among individuals, (2) whether the parasite load varies over time, (3) whether the parasite load has an effect on acoustic and visual signals, which are supposed to be important for female mate choice and (4) whether the parasite load influences the reproductive behaviour. We found that 60 % of our focal males were infested with an intestinal nematode of the genus Cosmocerca while the parasite load changed considerably over time. We found slight associations between the intensity of acoustic signals (advertisement calls), visual signals (colour and brightness contrasts) and parasite load. Non-infected males produced significantly lower pulse rates than parasitised males. As pulse rate has been shown to decrease with age, we suggest that males without parasites become older than infected males. Moreover, the visual contrasts of the frogs varied across natural backgrounds. An interaction between parasite infection and the background of the calling place affected the ventral colour contrast. This finding suggests that at least some males without parasites defend calling places that render them more conspicuousness to conspecifics than other potential positions would. There were no differences in several elements of reproductive behaviour between parasitised and healthy males. Further studies are necessary to find out whether parasite infection varies among populations, and whether at higher levels it would have a stronger influence on sexual signals, behaviour and lifetime fitness.