Social Cognition and the Neurobiology of Rodent Mate Choice

Synopsis

Various aspects of sociality, including mate choice, are dependent on social information. Mate choice is a social cognitive process that encompasses mechanisms for acquiring, processing, retaining and acting on social information. Social cognition includes the acquisition of social information about others (i.e., social recognition) and social information from others (i.e., social learning). Social cognition involves both assessing other individuals and their condition (e.g., health, infection status) and deciding about when and how to interact with them, thus, providing a frame-work for examining mate choice and its associated neurobiological mechanisms. In vertebrates, and in particular rodents, odors are an essential source of direct and indirect social information not only from others but also for others. Here, we briefly consider the relations between social cognition and olfactory-mediated mate choice in rodents. We briefly discuss aspects of: (1) social recognition of potential mates and the impact of infection threat on mate choice; (2) social learning and the utilization of the mate choices of others (“mate-choice copying”) including in the context of infection; and (3) the neurobiological mechanisms, with particular focus on particular the roles of the nonapeptide, oxytocin and the steroid hormones, estrogens, associated with social cognition and mate choice.

Introduction

The acquisition and use of social information underlies various aspects of social behavior and sociality. Animals need and seek social information to make adaptive decisions that determine their behavioral interactions with conspecifics. Social information can be provided either as direct signals from others and, or arise indirectly as cues or by-products produced by the behavior and decisions of others with similar needs and requirements (Danchin etal. 2004). Various aspects of sociality including, social behavior per se (i.e., interactions among conspecifics), social organization and networks, sexual behavior and mate choice involve the use of social information. Social information allows individuals to integrate their own behavior with that of social partners in a context-appropriate manner. This involves not only successfully assessing other individuals and their condition and behavior but also deciding whether, when, and how to interact with them.

Social information use is particularly important in determining who to avoid and whom to mate with (i.e., “mate choice”). Although mate choice has been described in a variety of manners and terminologies (reviewed in Edward 2015) there is a consistent, but often unstated, requirement for social information. Mate choice is considered as a social cognitive process that occurs when the effects of traits (i.e., signals/cues of attractiveness, condition, infection status) expressed in one sex lead either directly or indirectly to non-random selection by, and mating with, members of the opposite sex (see Jennions and Petrie 1997; Kirkpatrick etal. 2006). Here we briefly review the relations between social cognition, the use of social information and olfactory mediated mate choice in rodents. We specifically focus on how the detection and avoidance of pathogens and the mate choices of others influences individual mate choice and address the possible underlying neurobiological mechanisms.

Social cognition–social recognition and social learning

Social cognition refers to the mechanisms by which animals acquire, process, retain and act on social information (Seyfarth and Cheney 2015). Social cognition incorporates mechanisms for assessing, evaluating and responding to a broad range of cues and signals relevant to social behavior. Social cognition impinges on various aspects of social motivation and emotion and encompasses concepts such as; social discrimination and recognition, understanding of others’ relations, attention, decision making, social learning, emotion processing, in-group (familiar)/out-group (unfamiliar) categorization and mate choice (Happe etal. 2017).

Social cognition at its basic level involves the acquisition of information about others (i.e., social recognition) as well as information from others (i.e., social learning) combined with the processing and use of that social information in subsequent decision making (Choleris etal. 2009).

Social Recognition. Social recognition is the ability of an individual to distinguish conspecifics including potential social and mating partners, social threats and competitors, based on either innate responses to and/or past experience with, others. Social recognition incorporates rapid and flexible learning and memory to deal with the changeable social context and social information available.

Social Learning. Social learning can be defined as when “learning is influenced by observation of, or interaction with, another animal or its products” (Box 1984; Galef 1988; Heyes 1994). Social learning provides a valuable source of adaptive information allowing individuals to exploit the previous experience of others and to respond to plastic fluctuations in social and ecological conditions. Social recognition is often integral to the appropriate expression and utilization of social learning (e.g., subordinate recognizing and learning from a dominant). Social learning has been documented across various conditions ranging from where and what to eat (learning of food preferences), avoidance of aversive situations and individuals, to utilizing the mate choice decisions of others (i.e., “mate-choice copying”) (e.g., Galef 1988; Dugatkin 1992; Choleris etal. 2009, 2012; Kavaliers etal. 2006, 2017; Clipperton etal. 2008).

Social cognition and mate choice

Mate choice is a cognitive process that includes: (1) perceiving and receiving both direct and indirect signals and cues providing social information about potential mates; (2) integration and processing of the multimodal sensory inputs; (3) recognizing, searching for and discriminating between various individuals; and (4) deciding to mate with specific individuals (Cummings and Ramsey 2015). Mate choice is sensitive to an individual’s responsiveness (arousal and “sexual incentive motivation”) and multisensory discrimination abilities and entails turning arousal into sexual behavior (Kirkpatrick etal. 2006; Ǻgmo 2011). Mate choice is characterized by both preference (i.e., order in which an individual ranks potential mates (including their signals and cues) and choosiness (i.e., responsiveness to potential mates and amount of effort expended in choice) (Jennions and Petrie 1997; Edward 2015).

Olfactory mediated mate choice

Animals use various forms of sensory inputs to gain social information regarding potential mates. Social recognition and discrimination associated with mate choice involves the processing and recognition of distal and proximal multi-modal (e.g., olfactory, acoustic, visual. tactile, vibrational) sensory information. It has long been known that olfactory information is a particularly important component of sexual approach and mate choice in rodents (Beach 1942). Odors both provide genetically determined information about others and convey that information to others (Stowers and Tsuang-Han 2015). Some of the characteristics of olfactory information are stable across the lifetime (e.g., sex) while others are dynamic and change quickly with the environment and an individual’s social experience and condition. Odors provide a social index of current condition (e.g., infection status) and quality prior to any direct interactions and are crucial for the expression of the appetitive (i.e., pre- sexual, pre-copulatory) components of mate choice in many species (Johnston 2003; Hurst 2009; Petrulis 2013).

Olfactory mediated recognition ranges from category recognition including; sex, age and reproductive status (e.g., estrous phase, testosterone levels), social hierarchy (e.g., dominant, subordinate, level of aggression), genetic relatedness, familiarity, condition and quality (e.g., infection status, diet, microbiome composition, immune status) to true individual recognition (see reviews in Johnston 2003; Choleris etal. 2009). In rodents this recognition incorporates a variety of potential odor sources, their volatile and non-volatile products, and sophisticated detection mechanisms and receptors in the main and accessory olfactory systems and the vomeronasal organ (Baum and Bakker 2013; Stowers and Tsuang-Han 2015). This also provides animals mechanisms by which to detect and socially avoid parasites and infection (Boillat etal. 2015).

Impact of parasites and infection on mate choice

Every individual is infected by parasites (including bacteria and viruses) and pathogen avoidance and recognition are vital components of an animal’s ecology and social life (Kavaliers etal. 2004; Ezenwa etal. 2016). The costs of sociality imposed by infection risk can result in trade-offs between the benefits of engaging in social behaviors and the ability to deal with infection. The threat of infection has led to the concept of associative sociality, whereby social/sexual interactions are biased toward familiar healthy individuals coupled with the recognition and avoidance of either infected or potentially infected and unfamiliar individuals (Freeland 1976; Navarette and Fessler 2006; Fincher and Thornhill 2012; Kavaliers etal. 2014). Such preferences function to reduce risks of disease transmission (contagion indicator and behavioral immunity hypothesis) (Hart 1990; Able 1996; Schaller etal. 2015) and improve genetic disease resistance [parasite mediated sexual selection hypothesis (Hamilton and Zuk 1982)].

Social animals can undergo dispersal necessitating contacts and interactions with unknown conspecifics and the potential risk of infection. Choosing either an obviously sick or a behaviorally healthy “sub-clinically” (non-sick) infected mating partner is risky. An individual’s infection status can not only affect how its’ condition (health) is perceived by conspecifics but also can influence its own health, sexual responsiveness, social discrimination and mate choice (see Kavaliers etal. 2004; Beltran-Bech and Richard 2014). In addition, the roles of recent social history, individual experience and cognitive abilities and various social factors and biases in determining the effects of and responses to infection threat need to be taken into account. In changing environmental and social conditions static traits are not always reliable indicators of mate quality, necessitating a need for plastic, environmentally dependent mate choice and preferences.

The effect of infection upon mate choice involves consideration not only of the cues/signals and molecular and neurobiological mechanisms individuals use to distinguish between infected and uninfected individuals but also host behavioral and physiological immune response (e.g., competence, resistance, tolerance) to infection (Ezenwa etal. 2016). Resistance refers to an individuals’ ability to avoid, minimize or prevent infection and involves both behavioral and immunological responses. Tolerance on the other hand acts to reduce damage inflicted by pathogens. Although both of these factors influence the nature of the social information provided and the responses to social information, to date there has been minimal consideration of their specific impacts on mate choice. Rather the emphasis has been on the effects of either acute experimental infections or chronic parasitism with relatively little consideration of the roles of co-infection(s), multi-host and multi-parasite networks or prior, including perinatal, infection.

Parasites may affect their hosts by directly competing for resources, through immunoregulation, and/or altering trade-offs in investment between immunity and other core activities such as growth and reproduction, all of which can impact on behavior (Ezenwa etal. 2016). In rodents, infections have been shown to not only affect male host urine scent (odor) marking but also the quality and likely composition of the odor components (Zala etal. 2004; Lopes and Konig 2016). A variety of volatile and non-volatile compounds have been identified in mouse urine and related to two highly polymorphic gene complexes; the major histocompatibility complex (MHC) and the major urinary protein (MUP) cluster (Hurst 2009; Stowers and Tsuang-Han 2015). Non-volatile MUPs play roles as carriers of volatile ligands, and polymorphism of MUPs contributes to the diversity of chemicals in urine that are linked to individual recognition and condition (Hurst 2009). It has been suggested that infection-related changes in MHC class II gene complex linked immune function and volatile odor constituents and production may be linked to individual condition (e.g., Yamazaki etal. 1979; Potts etal. 1991; Hurst 2009; Raveh etal. 2014). By altering urine and other odors, parasites can directly affect the mating possibilities of the host as well as their social interactions in non-mating contexts.

Honest signaling of condition and health is thought to be of prime importance for female choice of a mating partner (Jennions and Petrie 1997). The imunocompetence hypothesis (ICHH) suggests that steroid hormones (testosterone) act as mediators of traits important for female choice while suppressing immune function and adaptively reallocating resources from immunity to reproduction and development (Folstad and Karter 1992; for limitations of the ICHH see Ashley and Demas 2017). As such urinary odor products that are linked to testosterone and are costly to produce may provide a reliable and honest index of male condition.

Avoidance of infected and parasitized individuals occurs in a broad social context and necessitates efficient recognition mechanisms. Female rodents can distinguish between the odors of sub-clinically infected (i.e., non-sick) and uninfected males displaying aversive responses to (i.e., stress and altered nociceptive (analgesic) responses) and avoidance of, the urinary odors of parasitized males. These analgesic responses and their anxiety/fearfulness/stress-associated behavioral correlates shift the motivational state of the females, eliciting a reduced interest in, and avoidance of, the aversive cues associated with the parasitized males, thereby facilitating the choice of uninfected males (Kavaliers etal. 2004).

Female rodents use odors to recognize, avoid and display aversive responses to individuals infected with a variety of macroparasites, microparasites, viruses, bacteria and their components (see reviews in Kavaliers etal. 2004; Beltran-Bech and Richard 2014). Females not only discriminate against the odors of infected males but also are more attracted to the odors of uninfected males than that of experimentally infected males. In simultaneous choice tests (infected vs non-infected) female mice displayed overall preferences for, and initial choice of, the urinary odors of uninfected males as well as marked aversive responses (i.e., analgesia and elevated corticosterone) to, and avoidance, of the urinary odors of asymptomatic males infected with a range of parasites (e.g., nematode, Kavaliers etal. 2006). The responses of the female mice incorporated changes in both preference and choosiness. In sequential and binary choice tests both pro-estrous and estrous females recognized and avoided the odors of infected males as well as the actual infected males (for discussion of the effects of experimental design on mate choice see Dougherty and Shuker 2015).

Female mice were able to differentiate between the urinary odors of males suubclinically infected with the enteric protozoan (coccidian) parasite, Eimeria vermiformis, at any early non-infective stage (non-infective pre-patent stage) from those males that were infective to others (patent stage), showing a greater aversion to infective males (Kavaliers etal. 1997). The stage of infection also affected the males’ interest in females with non-infective individuals showing a reduced, and infective males an enhanced interest in, and responses to, females and their odors. This preference shift likely incorporate infection related changes in arousal and sexual incentive motivation and illustrates the need to examine not only the responses to infected individuals but also the responses of the hosts themselves when considering infection and mate choice. Although male mate choice is less studied (Edward and Chapman 2011), males can also use odor cues to discriminate and display aversive responses to infected females (e.g., Kavaliers etal. 1998). In view of the significant sex differences in various neural and behavioral processes (Choleris etal. 2017) sex differences in both the effects of the actual infection and responses to infection need consideration.

Infection threat also rapidly decreased responses to and preferences for socially unfamiliar males, whereas the presence of unfamiliar individuals per se heightened sensitivity to and avoidance of infected and potentially infected individuals and their odors (Kavaliers etal. 2014). This is consistent with assortative sociality and in-group bias and out-group-avoidance, (in human terms ethnocentrism and xenophobia, respectively) (Navarette and Fessler 2006; Kavaliers and Choleris 2011, 2017). Thus, the immediate social conditions and infection threat can very rapidly affect and bias social preferences and female mate choice. As such pathogen threat can have general effects on how individuals interact with others, while at the same time perceptions of others can affect sensitivity to pathogen threat with their concomitant influences on mate choice and social choice and preferences and sociality in general.

Although, these investigations have been primarily limited to the laboratory, previous work with mice has shown that the results of odor preference tests are consistent with what happens in semi-natural environmental settings and reflect the appetitive and consummatory components of actual mating preferences (e.g., Wolff 1985; Drickamer etal. 2000; Raveh etal. 2014). There are however also findings from laboratory and semi-natural conditions, suggesting that odor avoidance apparently only moderately translates into avoidances of sexual behaviors and paternity (e.g., Zala etal. 2015). This indicates the need to consider multi-modal responses and the roles of sensory stimuli in addition to that of olfaction (e.g., Lopes and Konig 2016; Ǻgmo and Snoeren 2017). As well, the possibility that mate choice can be biased by sexual coercion along with by the occurrence of post copulatory mechanisms such as selective abortion, sperm competition and cryptic female choice needs to be examined.

In the wild odor preferences, combined with other sensory cues [e.g., ultrasonic vocalizations (Lopes and Konig 2016)], result in female mice being more likely to detect and locate healthy males. Although indirect mate choice is not directly equal to a sexual preference it can still lead to a biased mating if the initial choices removes a female from a less preferred male. As such male odor production and deposition may attract females to their territories with the subsequent olfactory mediated assessment of male condition and quality leading to rapid decisions regarding mate choice and subsequent sexual interactions. This possibility does not however preclude the need to consider the effects of the ecological (e.g., predators, food availability) and social context (e.g., prior experience, including that of infection and microbiome composition, degree of motivation, male availability, social networks and interactions, presence of other females) on female and likely male mate choice (Ǻgmo 2011, Edwards and Chapman 2011, Bertran-Bech and Richard 2014, Archie and Tung 2015, Cummings and Ramsey 2015). In particular there is mounting evidence that females and males may utilize the social information provided by the mate choice decisions of others (mate-choice copying) to determine their own mate choices.

Mate-choice copying

Individuals pay attention to what others are doing and in whom (e.g., potential mates) they are interested, thereby reducing the risks and uncertainty associated with their own choices (e.g., Galef, 1988; Dugatkin, 1992; Clipperton etal. 2008; Choleris etal. 2009; Kavaliers etal. 2017). The mate choice decisions of one individual can be influenced by either the actual or potential mate choice of another. Such non-independent mate choice where individuals gain information and socially learn about potential mates by observing conspecifics or their cues is termed “mate-choice copying”. Thus, when a female rat (the observer or copier) observes another female rat (the demonstrator or model) displaying sexual interest in a male rat (target), she subsequently remembers and prefers that male target when given a choice between two males (Galef etal. 2008). Mate choice copying involves using and processing direct and indirect social information from others (i.e., social learning from the “demonstrator”) as well as social information about others (i.e., social recognition of the “target” and demonstrator). The observer needs to recognize, select and integrate social information from the demonstrator and target and then make appropriate decisions regarding their own mate choice.

In the original formulation of mate-choice copying, it was indicated that females do not actually need to observe actual sexual interactions and mating but only an “apparent choice” (i.e., appetitive responses) (Pruett-Jones 1992). In the wild females are likely to detect a proxy of mate choice (e.g., odor interest and investigation) rather than observe the often very briefly performed active mating. As such, the natural social organization and interactions of mice (Latham and Mason 2004), provide opportunities for mate-choice copying to occur. The odors of a female that are associated with that of a male are a potential source of information that can be used to guide the social interests and mate choice of other females. Female mice attend to male scent marks and to deposit odors in response to male odors (Zala etal. 2004). Sexually naïve estrous female mice recognized and preferred the urinary odors of specific males that were associated with the odors of another estrous female over those of males that, either had no association, or were associated with the odors of non-estrous females. This socially learned odor preference lasted for at least 24 h and resulted in the choice of the specific male that was the odor source (Kavaliers etal. 2006, 2017). Odor based mate-choice copying has been now described in female Norway rats and deer mice as well as sexually naïve males (Galef etal. 2008; Kavaliers etal. in preparation).

Mate choice copying can override females’ innate preferences leading to the copying of what was previously a less preferred male (Dugatkin and Godin 1992, 1993). Estrus female mice normally prefer the odors of sexually aroused males (i.e., elevated testosterone) that have received prior exposure to estrous females over the odors of sexually naive unstimulated males (Zala etal. 2004). However, when the odor of another estrous female is associated with that of unstimulated male, that choice is shifted. The presence of the odors of an estrous female with that of the infected male attenuated the aversive (analgesic and elevated corticosterone) and avoidance responses normally shown by sexually naïve female mice resulting in a subsequent choice for the odors of that specific infected male (i.e., true individual recognition) (Kavaliers etal. 2006). Uninfected does not necessarily imply a better quality male (e.g., Adamo and Spiteri 2009). For example dominant male mice are more susceptible to Heligmosomoides polygyrus infection, displaying elevated testosterone levels and both reduced parasite clearance and higher parasite levels (Barnard etal. 1998). Here, using the putative interests/choice of another female for an infected male may be appropriate. However, mate-choice copying can also increase the risk of infection, comparative investigations with primates indicating that the incidence of socially contagious diseases is positively associated with social learning (McCabe etal. 2015). In this regard copying of the avoidance of non-preferred partners has also reported (Kavaliers etal. 2017). It is, thus, likely that mate-choice copying influences the expression of mate choice in a flexible and plastic manner according to the immediate social context.

Neurobiology of mate choice

The acquisition of social information has significant neurobehavioral effects (Choleris etal. 2009). This allows individuals to rapidly evaluate, integrate and respond to social information derived from a potential partner into appropriate mating related responses. These rapid responses involve a variety of neurobiological regulatory mechanisms associated with social/sexual behavior and motivation and social cognition. These mechanisms include: evolutionarily conserved neurotransmitters, in particular dopamine and serotonin in the “mesolimbic reward system” and “social behavior network” as well as other neurotransmitters associated with social recognition and social learning: opioid peptide systems; sex steroid hormones (testosterone and, in particular, estrogens); other steroid hormones (e.g., corticosteroids, neurosteroids); nonapeptide systems (oxytocin (OT), arginine-vasopressin (AVP) and their receptors) and other neurohormones associated with reproductive behaviors, as well as immune components and micobiome products (Choleris etal. 2009, 2012; O’Connell and Hofmann 2011; Gabor etal. 2012; Goodson 2013; Petrulis 2013; Ervin etal. 2015; Dumais and Veenema 2016; Ashley and Demas 2017; Lopes 2017). Like most organismal processes, the neurhormonal mechanisms associated with mate choice are evolutionarily constrained by their functions across multiple contexts.

Oxytocin, mate choice and social cognition

The hormone regulated mammalian nonapeptides, OT and AVP, are involved in mediating responses to, and the processing of, socially salient information including that associated with social recognition, social learning and social memory (Choleris etal. 2009; Kavaliers and Choleris 2011; Goodson 2013; Shamay-Tsoory and Abu-Akel 2016). OT is synthesized in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus with neurons projecting to various parts of the brain associated with social cognition and modulating behavior in sex-, brain-region- and context dependent manners (Mitre etal. 2016). OT receptors (OTR) in rodents are proposed to modulate a social salience network, a set of interconnected brain nuclei, including the social behavior network (e.g., medial amygdala and cortical and sub-cortical substrates such as; insular cortex, dorsal hippocampus, thalamus, paraventricular nucleus of the hypothalamus, piriform cortex and other olfactory regions) encoding the valence and incentive salience of social and sensory, including olfactory, cues (Goodson 2013; Johnson etal. 2017; Marlin and Fromeske 2017; and see Fig. 1). This allows OT to mediate responses to both positive and negative salient social information with the nature of the responses (i.e., approach or avoidance), dependent on the social context and nature of the social stimulus (DeDreu and Kert 2016; Shamy-Tsoory and Abu-Akel 2016).

In mice and rats, OT is involved in the mediation of social recognition (Ferguson etal. 2001a,b; Choleris etal. 2003, 2007 and reviewed by Gabor etal. 2012) and the recognition and avoidance of infected individuals and odors associated with them (Arakawa etal. 2010; Kavaliers and Choleris 2011). Female mice with deletions of the OT gene (OT knockout, OTKO mice), as well as those treated with an OT antagonist, were impaired in their recognition and avoidance of the odors of infected individuals, though not the odors of other threats (Kavaliers etal. 2004, 2006).

Odor information regarding condition and identity of the scent owners is detected by the vomeronasal and main olfactory systems and conveyed to amygdala and other central social network sites. OT in the medial amygdala has been shown to be critical for social recognition (Ferguson etal. 2001a; Choleris et al, 2003, 2007) and, thus, a likely target for the altered responses to infected males (Fig. 1). In addition, OT at the level of the pyriform cortex and anterior olfactory cortex is involved in the modulation of odor mediated social recognition and encoding the saliency of social stimuli (reviewed in Marlin and Froemke 2017).

OT is also involved in social learning (reviewed in Choleris etal. 2009) and the mediation of mate-choice copying. OTKO female mice and females treated with an OTR antagonist were impaired in their use of indirect social information and did not copy the odor based mate choices of other females (Kavaliers etal. 2006, 2017). This is suggestive of the role that OT has in increasing the positive salience of, and attention and approach to positive social stimuli in humans (DeDreu and Kert 2016; Shamay-Tsoory and Abu-Akel 2016). Female mice engaged in mate-choice copying at a time of enhanced social/sexual motivation and may be “trusting” the mate interests of other females. In humans, OT increases trust and information sharing among individuals that are from the same group (De Wilde etal. 2017). The bi-directional effects of OT on approach/avoidance according to social salience (Shamay-Tsoory and Abu-Akel 2016) could facilitate both pathogen avoidance and mate-choice copying.

Although the emphasis has been OT here is also evidence that AVP is involved in the mediation of social recognition, though likely more so in males than females (reviewed in Dumais and Veenema 2016). The roles of AVP in social cognition and responses to social information and sociality merit further consideration especially in relation to male mate choice and responses to pathogens.

The augmented salience of the demonstrator’s mate choice may also be associated with a perceived increased sexual incentive and reward value of the target. OT is associated with sexual motivation and sociosexual behaviors including the recognition and approach of males by females (Ǻgmo etal. 2008; Nakajima etal. 2014) and the facilitation of sexual reward (reviewed in; Carter 1992; Veening etal. 2015). OT modulates reward circuits through effects on dopamine, serotonin as well as opioid and endocannabinoid systems (Dolen etal. 2013; Wei etal. 2015). Changes in mu and kappa opioid activity were associated with the altered responses to female odors of males infected withE. vermiformis (Kavaliers etal. 1997). Whether or not these shifts in responses involve alterations in the functioning of OT systems remains to be determined, though results of recent studies have indicated that OT-mu opioid interactions can influence human social interaction (Dal Monte etal. 2017). As well, how polymorphisms in oxytocin systems and OTR influence individual differences in social contacts, mate choice and responses to pathogens need investigating.

Estrogens, Mate Choice and Social Cognition. Gonadal steroid hormones play an essential role in the regulation of social behaviors. Estrogenic systems through both rapid non-genomic and delayed and more protracted genomic mechanisms are involved in the regulation of the expression and utilization of social information (Clipperton etal. 2008; Choleris etal. 2009; Ervin etal. 2015). Estrogens are associated with all aspects of female and likely male mate choice ranging from social odor production to social recognition, social learning and ultimately sexual behavior (reviewed in Ervin etal. 2015). Female mice and rats adjust their responses to males and male olfactory cues according to their estrogen dependent sexual motivation and neural responsiveness (Ǻgmo 2011; Nomoto and Lima 2015; McHenry etal. 2017). As such estrogens are likely affecting the processing of social stimuli at multiple sites within the social brain network.

Social responses to odors involve multiple levels from the perception or detection of the odors to their activation of various central nuclei associated with the further processing of olfactory information, as well as expression of social behaviors. All of these levels of action present potential targets at which estrogens can have differential effects, either directly or through other neuromodulatory systems (Choleris etal. 2012; Gabor etal. 2012; Ervin etal. 2015). In relation to sexual behavior per se the rapid effects of estrogens have been related to an immediate increase in sexual motivation and appetitive approach behaviors while the more delayed effects are associated with changes in sexual performance (Cornil etal. 2015).

There are three better known estrogen receptors (ERs), ERα, ERβ and the G protein coupled ER 1 (GPER1) that are associated with sexual behavior, mate choice and social recognition (Ervin etal. 2015). ERα and GPER1 have been reported to rapidly facilitate social recognition and social learning whereas the effects of ERβ are less clear (Phan etal. 2015; Lymer etal. 2017). In regards to pathogen avoidance and mate choice ERα and ERβ gene deleted mice (ERαKO and ERβKO mice) were impaired in their olfactory-mediated social recognition of infected individuals and their ability to distinguish between familiar and unfamiliar individuals (reviewed in Choleris etal. 2009, 2012; Ervin etal. 2015). They were also impaired in their ability to distinguish between the odors of infected and uninfected males in choice tests, as well as in the aversive responses they displayed towards the odors of infected individuals (Kavaliers etal. 2004). These impairments were not due to differences in either olfactory sensitivity, sexual motivation, or stress responses supporting effects on cognitive processes.

The effects of ERs on social recognition and responses to infection threat involve OT. ERβ and GPER are implicated in the regulation of the synthesis and release of OT at the level of the hypothalamus (reviewed in Gabor etal. 2012; Ervin etal. 2015 and summarized in Fig. 1). All three receptors are expressed at the level of the medial amygdala where they enhance social recognition (Lymer etal. 2017) and likely are associated with the functioning of the OTR (reviewed in Gabor etal. 2012 and summarized in Fig. 1). As well estrogens in the PVN are involved in the determination of social recognition (in preparation). In female mice estrogens at the level of the medial preoptic area have also been associated with the rewarding effects of male odors facilitating dopamine release at the level of the ventral tegmental area (McHenry etal. 2017). As well, the rapid effects of estrogens through GPER1 associated actions as well as effects on other neuromodulatory systems associated with mate choice need to be considered. In addition, the roles of progesterone which is selectively associated with the indifference shown by diestrous female mice to MUP associated male odors, need to be addressed (Dey etal. 2015). The roles of other neuromodulators, including immune components that can affect behavior and are influenced by estrogens, and other regions in the social brain also need to be considered.

Conclusions

Mate choice is context and situation specific, and is biased by various social and cognitive factors including individual differences in cognitive abilities (Jennions and Petrie 1997; Verzijden etal. 2012: Cummings and Ramsey 2015). Choice can appear to be virtually non-existent or “irrational” under heightened sexual “arousal” and when there are either minimal benefits in choosing (e.g., minimal phenotypic variation among potential mates), the costs for discrimination are high and opportunities are limited (e.g., search costs, opportunity costs and trade-off with other preferences). The absence of obvious choice can result in an apparent passive acceptance of the first conspecific encountered apparently without either active sampling or discrimination between potential mates (Edward 2015). Despite these concerns social cognition is integral to mate choice. There is substantial evidence for the presence of both direct and indirect mate choice in a number of animal species and classes and its’ modulation by previous experience and current social conditions including pathogen and infection threat and the choices of others. Social cognition provides a frame-work for the investigation of mate-choice and addressing the underlying neurobiological mechanisms. As outlined here there is accumulating evidence that oxytocin and estrogens, in particular are associated with the acquisition, utilization and integration of olfactory and other social information and the expression of context appropriate mate choice.

Funding

Studies described here were supported by Natural Sciences and Engineering Research Council of Canada (NSERC) discovery grants [to E.C. NSERC grant number 400212 and M.K. NSERC grant number R0557A01]

References

Author notes