- Email: [email protected]
Towards meeting Tinbergen's challenge
Hormones and Behavior 60 (2011) 22–27
Contents lists available at ScienceDirect
Hormones and Behavior j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / y h b e h
Commentary
Towards meeting Tinbergen's challenge Alexander G. Ophir ⁎ Department of Zoology, Oklahoma State University, Stillwater, OK 74078, USA
a r t i c l e
i n f o
Article history: Received 8 February 2011 Revised 17 March 2011 Accepted 23 March 2011 Available online 7 April 2011 Keywords: Social behavior Mating system Grouping Finch Vole Social brain Lateral septum Vasopressin Vasotocin Oxytocin Mesotocin Territorial Anxiety Integrative biology
A half-century ago, the great pioneers of ethology (e.g., Tinbergen, 1951) and neuroscience (e.g., Hebb, D. O., 1949. The organisation of behaviour. Wiley-Interscience, New York.) recognized that the need to bridge the gap between the “ethologist” and the “physiologist” was crucial if we are to achieve a clear understanding of the behavior of the “intact animal.” Arguably among Tinbergen's greatest gifts to those of us interested in the study of behavior were his Four Questions (Tinbergen, 1963). Tinbergen outlined that behavior had many different sides, each of which could teach us something more about the subject of study. One could observe the same individual and ask several questions, with each providing independent answers from the others. These included: 1) “describing the course of evolution,” 2) the course of development, 3) “the genetics proper of behavior,” and 4) “the directional changes under the influence of natural selection” (Tinbergen, 1951). Tinbergen was clear that each question allowed a scientist to investigate a given behavior from a very different perspective; by looking at the same object from different angles, something unique and new about that object is revealed. As students, we have been taught to approach these different levels of analysis ⁎ 508 Life Sciences West Department of Zoology Oklahoma State University Stillwater, OK 74078, USA. Fax: + 1 405 744 7824. E-mail address: [email protected]. 0018-506X/$ – see front matter. Published by Elsevier Inc. doi:10.1016/j.yhbeh.2011.03.012
independently—this is particularly true for proximate and ultimate questions (Kennedy, J. S., 1992. The new antrhopomorphism. Cambridge University Press, Cambridge.; Krebs, J. R., Davies, N. B., 1997. Behavioural Ecology. Blackwell, Oxford.; Mayr, E., 1961. Cause and effect in biology. Science. 134, 1501–1506.; Williams, G. C., 1966. Adaptation and natural selection. Princeton University Press, Princeton.). However, understanding one level can tell us a great deal about the others (Thierry, B., 2005. Integrating proximate and ultimate causation: Just one more go! Current Science. 89, 1180–1183.), and Tinbergen himself noted that these modes of analyses were isolated only for convenience of description and analysis (Tinbergen, N., 1963. On aims and methods in ethology. Zeitschrift für Tierpsychologie. 20, 410–433). Since Tinbergen's time, integrative approaches in biology have steadily gained in popularity, which may reflect scientists' growing appreciation for behavior as a primary driving force in evolution. Perhaps ironically, the emphasis on integrative approaches, paired with increasing technological advances, has caused the distinctions Tinbergen outlined to coalesce. Multi-level approaches are increasingly more feasible; genetic and phenotypic engineering, for example, offer the opportunity to gain a better account of genetic, physiological, and neurological factors governing behavior. Such approaches offer great insight into the causes of both the evolution and behavior of Tinbergen's “intact animal.” Here I highlight some of
A.G. Ophir / Hormones and Behavior 60 (2011) 22–27
the work by Goodson and colleagues, with special focus on Kelly et al. (2011) published in this issue of Hormones and Behavior, which embodies this scientific framework. This set of studies has pioneered the hypothesis that septal peptides facilitate social grouping preferences. I offer my own speculation that attempts to find common denominators in neuropeptide control of social behavior by integrating this apparent “sociality continuum” with that of another related spectrum of social behavior, mating system. Integrating levels of analysis: estrildids In this issue, Kelly et al. (2011) build on work coming from their lab group that represents efforts toward achieving a deeper understanding of animal behavior by bringing together several approaches. This earlier work combines cross-species comparisons, genetic manipulation, an attempt to understand the physiological mechanisms that mold behavior, and efforts to consider these mechanisms as consequences of directional changes under the influence of natural selection. In an attempt to identify the mechanisms that promote flocking behavior in the zebra finch, a highly gregarious estrildid species, Kelly et al. (2011) elegantly demonstrate that social grouping preferences are under the direct control of vasotocin (VT) in the medial portion of the bed nucleus of the stria terminalis (BSTm) and its receptors (V1alike) in the lateral septum (LS). By use of antisense knockdown of the hormone at the source, and infusion of receptor antagonist at the target, Kelly et al. (2011) demonstrate that this circuit is integral for shaping social grouping preferences, but not affiliative preferences. An important inference from this study is that several related but independent mechanisms of “sociality” operate to promote social behavior (see below). Beyond modulating aggregation in zebra finches, this research group has shown that these populations of cells modulate valence for rewarding social stimuli (such as affiliation-related cues) but not punishing stimuli (such as social subjugation) with their work using the immediate early gene c-Fos (Goodson et al., 2009a; Goodson and Wang, 2006). Estrildid finches range in their affinity for grouping; some join flocks of hundreds, whereas others form selective territorial pairs. Goodson and his colleagues investigated five species of monogamous and bi-parental estrildid finches and demonstrated that gregarious birds appear to be more sensitive to VT in the BSTm-LS circuit compared to asocial finches. For instance, gregarious birds show high c-Fos activity in VT cells after exposure to conspecifics (Goodson and Wang, 2006). In contrast, territorial birds show decreased c-Fos activity to conspecifics unless the territorial bird is exposed to its partner, in which case VT neurons show increases in c-Fos. Furthermore, flocking species have more VT neurons in the BSTm, they have more active VT neurons in the BSTm, and they have more V1aR-like binding sites in the LS (Goodson et al., 2006; Goodson and Wang, 2006). However, pharmacological comparisons are needed to conclusively determine species differences in VT sensitivity. These species differences in mechanisms of social grouping extend beyond vasotocin to include at least one other nonapeptide, mesotocin (a common non-mammalian homologue for oxytocin). Distribution of oxytocin-like receptors predicts social grouping preferences across estrildid finches. For instance, the dorsal LS has higher OTR and the ventral LS has lower OTR density in gregarious finches (Goodson et al., 2009b), however the significance of dorso-ventral relationship has not yet been elucidated in finches or identified in other species. Moreover, infusions of an oxytocin antagonist reduce gregariousness in zebra finches (Goodson et al., 2009b), suggesting that septal mesotocin is necessary for social grouping in finches. Taken together, this research group has begun to characterize an emerging continuum between social and asocial species mediated by BSTm-LS nonapeptide interactions. This provides an important piece to the larger story that this and other labs have begun to construct: that nonapeptide expression
23
patterns are crucial to social structure and social behavior within and between species. Other models of social behavior: voles Estrildid finches are a promising emerging Avian model system for understanding mechanisms of social behavior. Although, the call for understanding human (or non-human) social behavior need not come from a mammalian model per se, the roles of these mechanisms in social interactions may be domain specific for certain species, and having taxonomically broad comparisons strengthens our understanding of the generalities of these mechanisms. Another promising model comes from a group of rodents from the genus Microtus. Indeed, voles have become one of the major models for understanding the prosocial influences of nonapeptides on social behavior. Much of this work has focused on individual and species differences in nonapeptide patterns in social organization and mating system. This body of work has been reviewed elsewhere (Carter et al., 1995; Insel and Young, 2001; Young and Wang, 2004; Young et al., 2005), and I will only briefly point out a few interesting points given the current backdrop. Monogamous prairie voles form intense attachment with partners and offspring, defend territories, and they are bi-parental (Getz and Hofmann, 1986; Getz et al., 1981, 1993; Insel et al., 1995; Thomas and Birney, 1979; Winslow et al., 1993). In contrast, non-monogamous voles do not form selective attachment, attempt to mate multiply, show seasonal variation in social grouping, and—like most mammals—are uni-parental (Beery et al., 2009; DeCoursey, 1957; Findley, 1951; Gruder-Adams and Getz, 1985; Madison, 1980; Madison et al., 1984; Wang et al., 1994; Webster and Brooks, 1981). With regard to nonapeptides, receptor density for both V1aR and oxytocin receptor (OTR) predicts social organization in monogamous prairie and pine voles and non-monogamous meadow and montane voles (Cho et al., 1999; Insel and Shapiro, 1992; Insel et al., 1994; Wang et al., 1998; Young et al., 1997). Manipulation of either hormone or their receptors influences the propensity to form bonds; infusion of nonapeptide agonists facilitates bonding, whereas receptor antagonists eliminate affiliative bonds (Cho et al., 1999; Lim and Young, 2004; Liu et al., 2001; Williams et al., 1994; Winslow et al., 1993). The primary focus of this work has been on the influence of peptides on the “pairbonding neural circuit” which includes the LS, the extended amygdalar complex (e.g., medial amygdala and BST), and other structures involved in reward such as the nucleus accumbens (NAcc) and ventral pallidum (VPall) (Young and Wang, 2004; Young et al., 2005). Although the septum has received comparatively less attention for its role in bonding, V1aR antagonists delivered to the LS eliminate bonding in prairie voles (Liu et al., 2001). Considering this result in the context of the work presented by Kelly et al. (2011) might lead to the pre-mature conclusion that septal vasopressin (the mammalian homologue of VT) mediates social bonding in prairie voles in the same manner as it mediates social grouping in estrildid finches; blockade of V1aR eliminates social affinity. Forms of sociality: distinction between affiliation and grouping There are, however, at least two important problems with equating (socially) affiliative prairie voles with (socially) gregarious finches. First, although convention has co-opted both terms under the larger term “sociality,” there is a fundamental difference between social affiliation and social grouping. For instance, an animal may form a bond with a single individual but be socially averse to groups. On the contrary, socially repose animals may demonstrate an inability to form meaningful bonds with a single individual. The fact that nonapeptides mediate two distinct aspects of social behavior may not be sheer coincidence (Goodson, 2008; Goodson and Bass, 2001),
24
A.G. Ophir / Hormones and Behavior 60 (2011) 22–27
however it is also important to fight the temptation to equate the mechanisms governing social grouping with those that mediate social bonding. The second problem with such a comparison is that closer examination of species differences in nonapeptides and their receptors reveals some principal differences between the two animal models. For example, Kelly et al. (2011) demonstrated that VT in the BSTm and septal V1a-like receptors do not modulate social contact— presumably a precursor to and indication of social bonds. Furthermore, V1a-like receptor expression in the LS is greater in gregarious estrildid finches, whereas monogamous prairie voles show lower V1aR densities than non-monogamous voles (Insel et al., 1994). The differences between the “prosocial” and “asocial” voles and finches extend beyond septal V1aR. Monogamous prairie voles have less septal OTR (Insel and Shapiro, 1992), meadow voles naturally have more vasopressin in the medial amygdala and BST (Wang, 1995), and paternal prairie voles have fewer vasopressin fibers in the septum compared to meadow vole fathers (Bamshad et al., 1993). It should be noted that male prairie vole virgins, have more vasopressin fibers than meadow vole virgins (Bamshad et al., 1993; Wang, 1995). Therefore, although monogamous prairie voles are more likely to form social bonds and V1aR antagonists block social bonding, meadow voles have more V1aR and OTR in the septum and more vasopressin in the BST. This begs the question: if septal vasopressin induces pairbonds, then why do meadow voles have more? In the BSTm-LS circuit discussed by Kelly et al., (2011) gregarious finches appear to have more pronounced VT-V1aR circuitry, whereas prairie voles appear to be more subdued in these expression patterns compared to their non-monogamous congener counterparts. The pattern and influence of septal peptides in voles, on first glance, does not adequately account for vole sociality, when sociality is so broadly defined. Re-integrating mating system One of the strengths of using estrildid finches is that comparison across this group of birds eliminates the variable of mating system and parental care; all the species that this lab group has studied vary in sociality but are bi-parental and monogamous. But perhaps mating system is an important part of the larger puzzle. Kelly et al.'s results suggest a social grouping continuum governed by VT in the BSTm-LS circuit. These structures are two important nodes in the “social brain” (Goodson, 2005; Newman, 1999; Swanson, 2000) and are probably modulating larger patterns of behavior. Indeed Kelly et al. (2011) propose an interesting idea—that social modulation of emotion and physiology is needed for normal expression of affiliation, aggression, and social preferences (e.g., mate preferences, novel/familiar preferences, or group size preferences). Such social modulation may be evident in receptor expression patterns of nonapeptides in their control of territoriality and flocking behavior. However to reduce these broad and contextually dependent behaviors to the one continuum is probably overly simplistic. It works well in the case of the estrildids because they vary on one axis (social grouping preferences) but do not vary on another important axis (namely, mating system). Invoking species differences to explain the incongruence between taxanomic groups is often justified, but it is also less satisfying. Embracing species differences while searching for general patterns, however, can lead to interesting insights and drive productive speculation. Could re-introducing mating system into the framework that Kelly et al. (2011) (and others) have constructed lead to broadly applicable emergent patterns? Contemplating this question forces a reconsideration of how the vole model has been portrayed. Prairie voles may be excellent models of social attachment, but perhaps they are poor models of gregarious social interactions. Although prairie voles live in social pairs (and may even live in larger phillopatric
groups; Getz et al., 1993; Jacquot and Solomon, 2004), for the most part they are highly territorial and defend these territories vigorously (Insel et al., 1995; Jacquot and Solomon, 2004; Winslow et al., 1993). Male meadow voles on the other hand are non-territorial (Madison, 1980), and seasonal variation in this species suggests that they increase their tolerance for social interactions to facilitate overwintering (Beery et al., 2009; Madison et al., 1984). In this sense prairie voles are much more like territorial estrildids and nonmonogamous meadow voles are more like gregarious finches. Moreover the pattern of peptides and their receptors with regard to the BSTm-LS circuit also supports this notion; meadow voles have more OTR and V1aR in the LS and vasopressin in the BST than prairie voles. What if we consider mating system and sociality to be orthogonal axes? Prairie voles are clearly more similar to all the estrildid finches than meadow voles in their form of offspring care and mating system; they form monogamous bonds with a single partner. However in terms of social grouping, prairie voles may be more appropriately compared to territorial finches while non-monogamous voles may be best placed on the end of the continuum nearer gregarious birds (Fig. 1). As discussed by Kelly et al., (2011) the social brain could be viewed as a weighting mechanism that modifies valences and sets up social contexts. Mechanisms important for mating system may produce social selectivity by promoting selective bonds (Fig. 1). However, phenotypic variance in the BSTm-LS circuit described by Kelly et al. (2011) may predispose animals to be prone or averse to large groups. In other words, regardless of their propensity to form social bonds, species that fall closer to the “gregarious” side of the continuum may be expected to be accustomed to larger groups (and therefore socially repose in these contexts), while the opposite would be true of species falling on the opposite end of that continuum (Fig. 1). The interactive effect of these two processes may independently (or semi-independently) shape the grouping preferences of territorial individuals— such as prairie voles and territorial estrildids—to be socially averse to most but socially attracted to a few. Meanwhile this interconnected network of social processing neural structures may also shape the behavior of monogamous gregarious individuals such as zebra finches to be socially prone to many, with special affinity for social/mating partners. On the other hand, nonmonogamous mating strategies should generally encourage social indiscrimination and social seeking, because mating opportunity should increase as a function of social interaction. While male aggression may be expected when sexual selection is strong, male territorial behavior may be relaxed when fitness is less dependent on male resource holding potential and more dependent on maximizing courtship and mating events with territorial females. Meadow voles appear to fit the latter condition. (This highlights an ancillary point: behavioral and neural sex differences should be expected.) The “social grouping axis” may therefore be driven by the BSTm-LS peptide system, with territorial animals demonstrating low OTR, V1aR and nonapeptide levels and gregarious animals exhibiting comparably high OTR, V1aR and nonapeptide levels. Flocking and overwintering behavior of zebra finches and meadow voles may be on one extreme of this continuum; territoriality in other finches and prairie voles might be best placed together on the other. Ultimately, different patterns of valences associated with general social preferences will be determined by the “social grouping axis” and should determine the extent to which animals prefer to live in large or small groups. A specialized form of social discrimination should be expected among monogamous species, when compared to non-monogamous ones. The second axis may be best characterized by the intimate link between social selectivity and mating system, in which the mechanisms governing bonding drive selectivity. V1aR antagonist in the LS eliminates partner preferences in prairie voles, but prairie voles have relatively low V1aR expression compared to non-bonding voles. Social
A.G. Ophir / Hormones and Behavior 60 (2011) 22–27
25
Fig. 1. Social grouping preferences (x-axis) and mating system (y-axis) can be viewed as independent but interacting variables that shape the general social behavior of animals. Mechanisms associated with social grouping (x-axis) are briefly summarized in the figure (and more extensively in the text). Mechanisms associated with bonding (y-axis) include nonapeptides and catecholamines involved in social recognition and reward (see text and references therein). Dashed arrows represent how an interaction between the two axes might produce differences is social selectivity based on anxiety reactions (anxious or repose) to large social groups.
recognition disruption has been suggested as a possible explanation for this result (Young et al., 2005). However, thinking about the LS as a social grouping mediator provides a new hypothesis for why antagonist eliminated bonding: blocking V1aR function could push animals to become so anti-social that bonds are impossible. It remains to be tested whether the mechanisms driving this hypothesized selective discrimination relate to the reward structures involved in the “pairbond neural circuit,” mechanisms governing recognition, shared structures of the social brain, or some other combination of neural mechanisms. Social behavioral titration through anxiety? The mechanisms that modulate anxiety may be one fruitful area to search for answers. Much of this type of work has suggested that social stimuli alter HPA axis activity, which in turn influences the formation of social preferences. Indeed, stress responses modulate and are modulated by peptide hormones, and may color the social context. Territorial animals are presumably socially averse by nature, and it seems reasonable to assume that social interaction could promote anxiety among this type of individual (Fig. 1, dashed lines). For example, male prairie voles show elevated corticosterone concentrations when housed in mixed-sex pairs or same-sex or mixed-sex groups (Klein et al., 1997). Gregarious individuals should fall on the other extreme in which social interaction should not promote anxiety. Mating system, however, would be expected to shape the form of social anxiety or social comfort exhibited by different species (Fig. 1). The context set up by natural stress-responses to social conditions, and the mechanisms therein, could promote selective bonding among monogamous individuals that are normally socially averse. Hormones related to anxiety have been implicated in prairie vole pairbonding and prairie voles have peculiar and abnormally high baseline levels of corticosterone suggesting a naturally overactive HPA axis (De Vries,
2002; Lim et al., 2006, 2007). Furthermore, as discussed by Kelly et al., (2011) vasopressin is an anxiogenic for many rodents including prairie voles. Taken together, these mechanisms may promote selective bonding through social anxiety. For instance, territorial monogamous species such as prairie voles appear to be socially averse in a general sense (i.e., HPA axis activated when placed in groups), but stress responses could drive specific bonding in contexts where bonding is possible (i.e., mixed-sex pairs or groups). On the other hand, it is possible that the stress-mediated social context could facilitate grouping behavior in generally social animals by placing individuals at ease in social contexts. For example, Kelly et al. (2011) demonstrated that VT acts as an anxiolytic in zebra finches, potentially reducing social anxiety. The anxio-social context may therefore predispose monogamous individuals to form unique mate bonds while also promoting grouping behavior. In other cases, stress responses among non-monogamous individuals may have little or no effect on selective social preferences. In meadow voles, for example, males housed alone, in same-sex pairs, mixed-sex pairs, same-sex groups or mixed-sex groups show consistently low serum corticosterone concentrations (Klein et al., 1997) indicating a lack of stress response to various social contexts. Although males are non-territorial, female territoriality likely restricts species grouping (Madison, 1980). Genetic manipulation can be used to introduce the mechanisms necessary to form selective bonds in males, and in this case males do indeed form selective bonds (Lim et al., 2004). Whether such a manipulation would affect general social attraction among males—essentially shifting them to be more similar to zebra finches—remains an untested question. Nevertheless, this framework suggests that the modulatory influences of the stress response-peptide interaction may alter the social context sufficiently so, such that animals that vary along two orthogonal axes— namely mating system and social grouping—fit into relatively independent and distinct behavioral categories.
26
A.G. Ophir / Hormones and Behavior 60 (2011) 22–27
Other promising model systems: peromyscus It should go without saying that much of what has been discussed here is speculative, and that experimental tests are required to determine the validity of the hypotheses outlined above. The two model systems discussed above are good places to begin. A third system that could be very promising is that of Peromyscus rodents. Like prairie, pine, meadow and montane voles, Peromyscus species vary in mating system: P. californicus is sexually monogamous, P. polianotus appears to demonstrate obligate monogamy, P. maniculatus and P. leucopus vary from facultative monogamy to promiscuity, and P. melanophrys is probably polygynous (Wolff, 1989). While almost nothing is known about the oxytocin-OTR system of Peromyscus, some interesting incongruities in the vasopressin-V1aR profiles exist with regard to the framework proposed above. For example, P. californicus has more vasopressin in the BST and more V1aR in the LS than P. leucopus (BesterMeredith et al., 1999; Insel et al., 1991). Although the sample sizes were rather low, (N = 2 male and N = 2 female per species), Turner et al. (2010) showed that V1aR expression across eight Peromyscus species does not appear to predict the mating system or social grouping preferences. Monogamy has evolved multiply within this clade and whether this incongruence is due to fundamental differences between sexual monogamy (P. californicus), obligate monogamy (P. polionotus and P. eremicus) and facultative monogamy (P. maniculatus and P. leucopus), or the relationship between aggressive behavior and social spacing (c.f., Goodson and Bass, 2001) remains to be determined. Although on first glance the Peromyscus system appears to refute the hypotheses outlined in the current commentary, it may provide a profound opportunity to more fully explore the interaction between mating system and social grouping because some Peromyscus species appear to demonstrate great plasticity in each behavioral domain. For example, the social grouping tendencies for many of the species described by Turner et al. (2010) varies by season and by social density; differential day light conditions and/or social density can shift the mating system and the social grouping tendencies (e.g., Kleiman, 1977; Mineau and Madison, 1977; Wolff, 1989). Thus, maintaining animals under long days or at low densities may induce septal up- or downregulation of V1aR differentially across the clade, and could account for some of the intriguing results presented in Turner et al. (2010).
Tinbergen's challenge Tinbergen pushed the scientific community to gain a deeper understanding of behavior by combining efforts to explore behavior from multiple vantage points. Indeed, he emphasized that behavior of the whole animal cannot be fully understood unless we consider the multifaceted nature of behavior. In this view, the best way to understand the mechanisms that mediate decisions and influence behavior is to consider the ultimate functions of behavior. The best way to understand how adaptations evolve and are constrained from evolving is to appreciate the proximate substrates that govern behavior. Each answer is better informed by asking questions at different levels of analysis. By investigating the genetic and physiological mechanisms that shape individual behavior over the backdrop of comparing neural phenotypes across species, Kelly et al. (2011) provides an excellent example of Tinbergen's vision. In a call to arms, he wrote “I should like to emphasize that future work [on understanding the neurobiology of behavior] could only be done by workers who are fully acquainted with the instinctive behaviour as a whole and with its analysis, and at the same time are in command of neurophysiological methods and techniques. … Our science is suffering from a serious lack of students with these qualifications, and it is an urgent task of ethologists and neurophysiologists to join efforts in the training of ‘etho-physiologists’.” (Tinbergen, 1951). The work presented in Kelly et al. (2011) broadens our understanding of the mechanisms of social behavior, provokes a
reconsideration of traditionally conceived ideas of sociality, and represents a significant step toward meeting Tinbergen's challenge.
References Bamshad, M., Novak, M.A., DeVries, G.J., 1993. Sex and species differences in the vasopressin innervation of sexually naïve and parental prairie voles, Microtus ochrogaster and meadow voles. Microtus pennsylvanicus. J. Neuroendocrinol. 5, 247–255. Beery, A.K., Routman, D.M., Zucker, I., 2009. Same-sex social behavior in meadow voles: multiple and rapid formation of attachments. Physiol. Behav. 97, 52–57. Bester-Meredith, J.K., Young, L.J., Marler, C.A., 1999. Species differences in paternal behavior and aggression in Peromyscus and their associations with vasopressin immunoreactivity and receptors. Horm. Behav. 36, 25–38. Carter, C.S., DeVries, A.C., Getz, L.L., 1995. Physiological substrates of mammalian monogamy: the prairie vole model. Neurosci. Biobehav. Rev. 19, 303–314. Cho, M.M., DeVries, A.C., Williams, J.R., Carter, C.S., 1999. The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). Behav. Neurosci. 113, 1071–1079. De Vries, A.C., 2002. Interaction among social enviornment, the hypothalamic– pituitary–adrenal axis, and behavior. Horm. Behav. 41, 405–413. DeCoursey, G.E., 1957. Identification, ecology and reproduction of Microtus in Ohio. J. Mammal. 38, 44–52. Findley, J.S., 1951. Habitat preferences of four species of Microtus in Jackson Hole, Wyoming. J. Mammalogy 32, 118–120. Getz, L.L., Hofmann, J.E., 1986. Social organization in free-living prairie voles, Microtus ochrogaster. Behav. Ecol. Sociobiol. 18, 275–282. Getz, L.L., Carter, C.S., Gavish, L., 1981. The mating system by the prairie vole, Microtus ochrogaster. Behav. Ecol. Sociobiol. 8, 189–194. Getz, L.L., McGuire, B., Pizzuto, T., Hofmann, J., Frase, B., 1993. Social organization of the prairie vole (Microtus ochrogaster). J. Mammal. 74, 44–58. Goodson, J.L., 2005. The vertebrate social behavior network: evolutionary themes and variations. Horm. Behav. 48, 11–22. Goodson, J.L., 2008. Nonapeptides and the evolutionary patterning of sociality. Prog. Brain Res. 170, 3–15. Goodson, J.L., Bass, A.H., 2001. Social behavior functions and related anatomical characteristics of vasotocin/vasopressin systems in vertebrates. Brain Res. Rev. 35, 246–265. Goodson, J.L., Evans, A.K., Wang, Y., 2006. Neuropeptide bidning reflects convergent and divergent evolution in species-typical group sizes. Horm. Behav. 50, 223–236. Goodson, J.L., Rinaldi, J., Kelly, A.M., 2009a. Vasotocin neurons in the bed nucleus of the stria terminalis preferntially process social information and exhibit properties that dichotomize sourting and non-courting phenotypes. Horm. Behav. 55, 197–202. Goodson, J.L., Schrock, S.E., Klatt, J.D., Kabelik, D., Kingsbury, M.A., 2009b. Mesotocin and nonapeptide receptors promote estrildid flocking behavior. Science 325, 862–866. Goodson, J.L., Wang, Y., 2006. Valence-sensitive neurons exhibit divergent functional profiles in gregarious and asoical species. Proc. Nat'l. Acad. Sci. USA 103, 17013–17017. Gruder-Adams, S., Getz, L.L., 1985. Comparison of the mating system and paternal behavior in Microtus ochrogaster and M. pennsylvanicus. J. Mammal. 66, 165–167. Hebb, D.O., 1949. The Organisation of Behaviour. Wiley-Interscience, New York. Insel, T.R., Gelhard, R., Shapiro, L.E., 1991. The comparative distribution of forebrain receptors for neurohypophyseal peptides in monogamous and polygamous mice. Neuroscience 43, 623–630. Insel, T.R., Preston, S., Winslow, J.T., 1995. Mating in the monogamous male: behavioral consequences. Physiol. Behav. 57, 615–627. Insel, T.R., Shapiro, L.E., 1992. Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proc. Nat'l. Acad. Sci. USA 89, 5981–5985. Insel, T.R., Wang, Z.X., Ferris, C.F., 1994. Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents. J. Neurosci. 14, 5381–5392. Insel, T.R., Young, L.J., 2001. The neurobiology of attachment. Nat. Rev. Neurosci. 2, 129–136. Jacquot, J.J., Solomon, N.G., 2004. Experimental manipulation of territory occupancy: effects on immigration of female prairie voles. J. Mammal. 85, 1009–1014. Kelly, A.M., Kingsbury, M.A., Hoffbuhr, K., Schrock, S.E., Waxman, B., Kabelik, D., Thompson, R.R., Goodson, J.L., 2011. Vasotocin neurons and septal V1a-like receptors potently modulate songbird flocking and responses to novelty. Horm. Behav. 60, 12–21. Kennedy, J.S., 1992. The New Antrhopomorphism. Cambridge University Press, Cambridge. Kleiman, D.G., 1977. Monogamy In Mammals. Q. Rev. Biol. 52, 39–69. Klein, S.L., Hairston, J.E., De Vries, A.C., Nelson, R.J., 1997. Social enviornment and steroid hormones affect species and sex differences in immune function among voles. Horm. Behav. 32, 30–39. Krebs, J.R., Davies, N.B., 1997. Behavioural Ecology. Blackwell, Oxford. Lim, M.M., Tsivkovskaia, N.O., Bai, Y., Young, L.J., Ryabinin, A.E., 2006. Distribution of corticotropin-releasing factor and urocortin 1 in the vole brain. Brain Behav. Evol. 68, 229–240. Lim, M.M., Liu, Y., Ryabinin, A.E., Bai, Y., Wang, Z., Young, L.J., 2007. CRF receptors in the nucleus accumbens modulate partner preference in prairie voles. Horm. Behav. 51, 508–515.
A.G. Ophir / Hormones and Behavior 60 (2011) 22–27 Lim, M.M., Wang, Z.X., Olazabal, D.E., Ren, X.H., Terwilliger, E.F., Young, L.J., 2004. Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 429, 754–757. Lim, M.M., Young, L.J., 2004. Vasopressin-dependent neural circuits underlying pair bond formation in the monogamous prairie vole. Neuroscience 125, 35–45. Liu, Y., Curtis, J.T., Wang, Z.X., 2001. Vasopressin in the lateral septum regulates pair bond formation in male prairie voles (Microtus ochrogaster). Behav. Neurosci. 115, 910–919. Madison, D.M., 1980. Space use and social structure in meadow voles, Microtus pennsylvanicus. Behav. Ecol. Sociobiol. 7, 65–71. Madison, D.M., FitzGerald, R.W., McShea, W.J., 1984. Dynamics of social nesting in overwintering meadow voles (Microtus pennsylvanicus): possible consequences for population cycling. Behav. Ecol. Sociobiol. 15, 9–17. Mayr, E., 1961. Cause and effect in biology. Science 134, 1501–1506. Mineau, P., Madison, D., 1977. Radiotracking of Peromyscus leucopus. Can. J. Zool. 55, 465–468. Newman, S.W., 1999. The medial extended amygdala in male reproductive behavior: a node in the mammalian social behavior network. Ann. N.Y. Acad. Sci. 877, 242–257. Swanson, L.W., 2000. Cerebral hemisphere regulation of motivated behavior. Brain Res. 886, 113–164. Thierry, B., 2005. Integrating proximate and ultimate causation: just one more go! Curr. Sci. 89, 1180–1183. Thomas, J.A., Birney, E.C., 1979. Parental care and mating system of the prairie vole, Microtus ochrogaster. Behav. Ecol. Sociobiol. 5, 171–186. Tinbergen, N., 1951. The Study of Instinct. Oxford University Press, New York. Tinbergen, N., 1963. On aims and methods in ethology. Z. Tierpsychol. 20, 410–433. Turner, L.M., Young, A.Y., Rompler, H., Schoneberg, T., Phelps, S.M., Hoekstra, H.E., 2010. Monogamy evolves through multiple mechanisms: evidence from V1aR in deer mice. Mol. Biol. Evol. 27, 1269–1278.
27
Wang, Z., 1995. Species differences in the vasopressin-immunoreactive pathways in the bed nucleus of the stria terminalis and medial amygdaloid nucleus in prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus). Behav. Neurosci. 109, 305–311. Wang, Z.X., Smith, W., Major, D.E., DeVries, G.J., 1994. Sex and species differences in the effects of cohabitation on vasopressin messenger RNA expression in the bed nucleus of the stria terminalis in prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus). Brain Res. 650, 212–218. Wang, Z.X., Young, L.J., De Vries, G.J., Insel, T.R., 1998. Voles and vasopressin: a review of molecular, cellular, and behavioral studies of pair bonding and paternal behaviors. Advan. Brain Vasopressin 483–499. Webster, A.B., Brooks, R.J., 1981. Social behavior of Microtus pennsylvanicus in relation to seasonal changes in demography. J. Mammal. 62, 738–751. Williams, G.C., 1966. Adaptation and Natural Selection. Princeton University Press, Princeton. Williams, J.R., Insel, T.R., Harbaugh, C.R., Carter, C.S., 1994. Oxytocin administered centrally facilitates formation of a partner preference in female prairie voles. J. Neuroendocrinol. 6, 247–250. Winslow, J.T., Hastings, N., Carter, C.S., Harbaugh, C.R., Insel, T.R., 1993. A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365, 545–548. Wolff, J.O., 1989. Social Behavior. Advances in the Study of Peromyscus (Rodentia). Texase Tech University Press, Lubbock. Young, L.J., Wang, Z.X., 2004. The neurobiology of pair bonding. Nat. Neurosci. 7, 1048–1054. Young, L.J., Winslow, J.T., Nilsen, R., Insel, T.R., 1997. Species differences in V1a receptor gene expression in monogamous and nonmonogamous voles: behavioral consequences. Behav. Neurosci. 111, 599–605. Young, L.J., Young, A.Z.M., Hammock, E.A.D., 2005. Anatomy and neurochemistry of the pair bond. J. Comp. Neurol. 493, 51–57.
Contents lists available at ScienceDirect
Hormones and Behavior j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / y h b e h
Commentary
Towards meeting Tinbergen's challenge Alexander G. Ophir ⁎ Department of Zoology, Oklahoma State University, Stillwater, OK 74078, USA
a r t i c l e
i n f o
Article history: Received 8 February 2011 Revised 17 March 2011 Accepted 23 March 2011 Available online 7 April 2011 Keywords: Social behavior Mating system Grouping Finch Vole Social brain Lateral septum Vasopressin Vasotocin Oxytocin Mesotocin Territorial Anxiety Integrative biology
A half-century ago, the great pioneers of ethology (e.g., Tinbergen, 1951) and neuroscience (e.g., Hebb, D. O., 1949. The organisation of behaviour. Wiley-Interscience, New York.) recognized that the need to bridge the gap between the “ethologist” and the “physiologist” was crucial if we are to achieve a clear understanding of the behavior of the “intact animal.” Arguably among Tinbergen's greatest gifts to those of us interested in the study of behavior were his Four Questions (Tinbergen, 1963). Tinbergen outlined that behavior had many different sides, each of which could teach us something more about the subject of study. One could observe the same individual and ask several questions, with each providing independent answers from the others. These included: 1) “describing the course of evolution,” 2) the course of development, 3) “the genetics proper of behavior,” and 4) “the directional changes under the influence of natural selection” (Tinbergen, 1951). Tinbergen was clear that each question allowed a scientist to investigate a given behavior from a very different perspective; by looking at the same object from different angles, something unique and new about that object is revealed. As students, we have been taught to approach these different levels of analysis ⁎ 508 Life Sciences West Department of Zoology Oklahoma State University Stillwater, OK 74078, USA. Fax: + 1 405 744 7824. E-mail address: [email protected]. 0018-506X/$ – see front matter. Published by Elsevier Inc. doi:10.1016/j.yhbeh.2011.03.012
independently—this is particularly true for proximate and ultimate questions (Kennedy, J. S., 1992. The new antrhopomorphism. Cambridge University Press, Cambridge.; Krebs, J. R., Davies, N. B., 1997. Behavioural Ecology. Blackwell, Oxford.; Mayr, E., 1961. Cause and effect in biology. Science. 134, 1501–1506.; Williams, G. C., 1966. Adaptation and natural selection. Princeton University Press, Princeton.). However, understanding one level can tell us a great deal about the others (Thierry, B., 2005. Integrating proximate and ultimate causation: Just one more go! Current Science. 89, 1180–1183.), and Tinbergen himself noted that these modes of analyses were isolated only for convenience of description and analysis (Tinbergen, N., 1963. On aims and methods in ethology. Zeitschrift für Tierpsychologie. 20, 410–433). Since Tinbergen's time, integrative approaches in biology have steadily gained in popularity, which may reflect scientists' growing appreciation for behavior as a primary driving force in evolution. Perhaps ironically, the emphasis on integrative approaches, paired with increasing technological advances, has caused the distinctions Tinbergen outlined to coalesce. Multi-level approaches are increasingly more feasible; genetic and phenotypic engineering, for example, offer the opportunity to gain a better account of genetic, physiological, and neurological factors governing behavior. Such approaches offer great insight into the causes of both the evolution and behavior of Tinbergen's “intact animal.” Here I highlight some of
A.G. Ophir / Hormones and Behavior 60 (2011) 22–27
the work by Goodson and colleagues, with special focus on Kelly et al. (2011) published in this issue of Hormones and Behavior, which embodies this scientific framework. This set of studies has pioneered the hypothesis that septal peptides facilitate social grouping preferences. I offer my own speculation that attempts to find common denominators in neuropeptide control of social behavior by integrating this apparent “sociality continuum” with that of another related spectrum of social behavior, mating system. Integrating levels of analysis: estrildids In this issue, Kelly et al. (2011) build on work coming from their lab group that represents efforts toward achieving a deeper understanding of animal behavior by bringing together several approaches. This earlier work combines cross-species comparisons, genetic manipulation, an attempt to understand the physiological mechanisms that mold behavior, and efforts to consider these mechanisms as consequences of directional changes under the influence of natural selection. In an attempt to identify the mechanisms that promote flocking behavior in the zebra finch, a highly gregarious estrildid species, Kelly et al. (2011) elegantly demonstrate that social grouping preferences are under the direct control of vasotocin (VT) in the medial portion of the bed nucleus of the stria terminalis (BSTm) and its receptors (V1alike) in the lateral septum (LS). By use of antisense knockdown of the hormone at the source, and infusion of receptor antagonist at the target, Kelly et al. (2011) demonstrate that this circuit is integral for shaping social grouping preferences, but not affiliative preferences. An important inference from this study is that several related but independent mechanisms of “sociality” operate to promote social behavior (see below). Beyond modulating aggregation in zebra finches, this research group has shown that these populations of cells modulate valence for rewarding social stimuli (such as affiliation-related cues) but not punishing stimuli (such as social subjugation) with their work using the immediate early gene c-Fos (Goodson et al., 2009a; Goodson and Wang, 2006). Estrildid finches range in their affinity for grouping; some join flocks of hundreds, whereas others form selective territorial pairs. Goodson and his colleagues investigated five species of monogamous and bi-parental estrildid finches and demonstrated that gregarious birds appear to be more sensitive to VT in the BSTm-LS circuit compared to asocial finches. For instance, gregarious birds show high c-Fos activity in VT cells after exposure to conspecifics (Goodson and Wang, 2006). In contrast, territorial birds show decreased c-Fos activity to conspecifics unless the territorial bird is exposed to its partner, in which case VT neurons show increases in c-Fos. Furthermore, flocking species have more VT neurons in the BSTm, they have more active VT neurons in the BSTm, and they have more V1aR-like binding sites in the LS (Goodson et al., 2006; Goodson and Wang, 2006). However, pharmacological comparisons are needed to conclusively determine species differences in VT sensitivity. These species differences in mechanisms of social grouping extend beyond vasotocin to include at least one other nonapeptide, mesotocin (a common non-mammalian homologue for oxytocin). Distribution of oxytocin-like receptors predicts social grouping preferences across estrildid finches. For instance, the dorsal LS has higher OTR and the ventral LS has lower OTR density in gregarious finches (Goodson et al., 2009b), however the significance of dorso-ventral relationship has not yet been elucidated in finches or identified in other species. Moreover, infusions of an oxytocin antagonist reduce gregariousness in zebra finches (Goodson et al., 2009b), suggesting that septal mesotocin is necessary for social grouping in finches. Taken together, this research group has begun to characterize an emerging continuum between social and asocial species mediated by BSTm-LS nonapeptide interactions. This provides an important piece to the larger story that this and other labs have begun to construct: that nonapeptide expression
23
patterns are crucial to social structure and social behavior within and between species. Other models of social behavior: voles Estrildid finches are a promising emerging Avian model system for understanding mechanisms of social behavior. Although, the call for understanding human (or non-human) social behavior need not come from a mammalian model per se, the roles of these mechanisms in social interactions may be domain specific for certain species, and having taxonomically broad comparisons strengthens our understanding of the generalities of these mechanisms. Another promising model comes from a group of rodents from the genus Microtus. Indeed, voles have become one of the major models for understanding the prosocial influences of nonapeptides on social behavior. Much of this work has focused on individual and species differences in nonapeptide patterns in social organization and mating system. This body of work has been reviewed elsewhere (Carter et al., 1995; Insel and Young, 2001; Young and Wang, 2004; Young et al., 2005), and I will only briefly point out a few interesting points given the current backdrop. Monogamous prairie voles form intense attachment with partners and offspring, defend territories, and they are bi-parental (Getz and Hofmann, 1986; Getz et al., 1981, 1993; Insel et al., 1995; Thomas and Birney, 1979; Winslow et al., 1993). In contrast, non-monogamous voles do not form selective attachment, attempt to mate multiply, show seasonal variation in social grouping, and—like most mammals—are uni-parental (Beery et al., 2009; DeCoursey, 1957; Findley, 1951; Gruder-Adams and Getz, 1985; Madison, 1980; Madison et al., 1984; Wang et al., 1994; Webster and Brooks, 1981). With regard to nonapeptides, receptor density for both V1aR and oxytocin receptor (OTR) predicts social organization in monogamous prairie and pine voles and non-monogamous meadow and montane voles (Cho et al., 1999; Insel and Shapiro, 1992; Insel et al., 1994; Wang et al., 1998; Young et al., 1997). Manipulation of either hormone or their receptors influences the propensity to form bonds; infusion of nonapeptide agonists facilitates bonding, whereas receptor antagonists eliminate affiliative bonds (Cho et al., 1999; Lim and Young, 2004; Liu et al., 2001; Williams et al., 1994; Winslow et al., 1993). The primary focus of this work has been on the influence of peptides on the “pairbonding neural circuit” which includes the LS, the extended amygdalar complex (e.g., medial amygdala and BST), and other structures involved in reward such as the nucleus accumbens (NAcc) and ventral pallidum (VPall) (Young and Wang, 2004; Young et al., 2005). Although the septum has received comparatively less attention for its role in bonding, V1aR antagonists delivered to the LS eliminate bonding in prairie voles (Liu et al., 2001). Considering this result in the context of the work presented by Kelly et al. (2011) might lead to the pre-mature conclusion that septal vasopressin (the mammalian homologue of VT) mediates social bonding in prairie voles in the same manner as it mediates social grouping in estrildid finches; blockade of V1aR eliminates social affinity. Forms of sociality: distinction between affiliation and grouping There are, however, at least two important problems with equating (socially) affiliative prairie voles with (socially) gregarious finches. First, although convention has co-opted both terms under the larger term “sociality,” there is a fundamental difference between social affiliation and social grouping. For instance, an animal may form a bond with a single individual but be socially averse to groups. On the contrary, socially repose animals may demonstrate an inability to form meaningful bonds with a single individual. The fact that nonapeptides mediate two distinct aspects of social behavior may not be sheer coincidence (Goodson, 2008; Goodson and Bass, 2001),
24
A.G. Ophir / Hormones and Behavior 60 (2011) 22–27
however it is also important to fight the temptation to equate the mechanisms governing social grouping with those that mediate social bonding. The second problem with such a comparison is that closer examination of species differences in nonapeptides and their receptors reveals some principal differences between the two animal models. For example, Kelly et al. (2011) demonstrated that VT in the BSTm and septal V1a-like receptors do not modulate social contact— presumably a precursor to and indication of social bonds. Furthermore, V1a-like receptor expression in the LS is greater in gregarious estrildid finches, whereas monogamous prairie voles show lower V1aR densities than non-monogamous voles (Insel et al., 1994). The differences between the “prosocial” and “asocial” voles and finches extend beyond septal V1aR. Monogamous prairie voles have less septal OTR (Insel and Shapiro, 1992), meadow voles naturally have more vasopressin in the medial amygdala and BST (Wang, 1995), and paternal prairie voles have fewer vasopressin fibers in the septum compared to meadow vole fathers (Bamshad et al., 1993). It should be noted that male prairie vole virgins, have more vasopressin fibers than meadow vole virgins (Bamshad et al., 1993; Wang, 1995). Therefore, although monogamous prairie voles are more likely to form social bonds and V1aR antagonists block social bonding, meadow voles have more V1aR and OTR in the septum and more vasopressin in the BST. This begs the question: if septal vasopressin induces pairbonds, then why do meadow voles have more? In the BSTm-LS circuit discussed by Kelly et al., (2011) gregarious finches appear to have more pronounced VT-V1aR circuitry, whereas prairie voles appear to be more subdued in these expression patterns compared to their non-monogamous congener counterparts. The pattern and influence of septal peptides in voles, on first glance, does not adequately account for vole sociality, when sociality is so broadly defined. Re-integrating mating system One of the strengths of using estrildid finches is that comparison across this group of birds eliminates the variable of mating system and parental care; all the species that this lab group has studied vary in sociality but are bi-parental and monogamous. But perhaps mating system is an important part of the larger puzzle. Kelly et al.'s results suggest a social grouping continuum governed by VT in the BSTm-LS circuit. These structures are two important nodes in the “social brain” (Goodson, 2005; Newman, 1999; Swanson, 2000) and are probably modulating larger patterns of behavior. Indeed Kelly et al. (2011) propose an interesting idea—that social modulation of emotion and physiology is needed for normal expression of affiliation, aggression, and social preferences (e.g., mate preferences, novel/familiar preferences, or group size preferences). Such social modulation may be evident in receptor expression patterns of nonapeptides in their control of territoriality and flocking behavior. However to reduce these broad and contextually dependent behaviors to the one continuum is probably overly simplistic. It works well in the case of the estrildids because they vary on one axis (social grouping preferences) but do not vary on another important axis (namely, mating system). Invoking species differences to explain the incongruence between taxanomic groups is often justified, but it is also less satisfying. Embracing species differences while searching for general patterns, however, can lead to interesting insights and drive productive speculation. Could re-introducing mating system into the framework that Kelly et al. (2011) (and others) have constructed lead to broadly applicable emergent patterns? Contemplating this question forces a reconsideration of how the vole model has been portrayed. Prairie voles may be excellent models of social attachment, but perhaps they are poor models of gregarious social interactions. Although prairie voles live in social pairs (and may even live in larger phillopatric
groups; Getz et al., 1993; Jacquot and Solomon, 2004), for the most part they are highly territorial and defend these territories vigorously (Insel et al., 1995; Jacquot and Solomon, 2004; Winslow et al., 1993). Male meadow voles on the other hand are non-territorial (Madison, 1980), and seasonal variation in this species suggests that they increase their tolerance for social interactions to facilitate overwintering (Beery et al., 2009; Madison et al., 1984). In this sense prairie voles are much more like territorial estrildids and nonmonogamous meadow voles are more like gregarious finches. Moreover the pattern of peptides and their receptors with regard to the BSTm-LS circuit also supports this notion; meadow voles have more OTR and V1aR in the LS and vasopressin in the BST than prairie voles. What if we consider mating system and sociality to be orthogonal axes? Prairie voles are clearly more similar to all the estrildid finches than meadow voles in their form of offspring care and mating system; they form monogamous bonds with a single partner. However in terms of social grouping, prairie voles may be more appropriately compared to territorial finches while non-monogamous voles may be best placed on the end of the continuum nearer gregarious birds (Fig. 1). As discussed by Kelly et al., (2011) the social brain could be viewed as a weighting mechanism that modifies valences and sets up social contexts. Mechanisms important for mating system may produce social selectivity by promoting selective bonds (Fig. 1). However, phenotypic variance in the BSTm-LS circuit described by Kelly et al. (2011) may predispose animals to be prone or averse to large groups. In other words, regardless of their propensity to form social bonds, species that fall closer to the “gregarious” side of the continuum may be expected to be accustomed to larger groups (and therefore socially repose in these contexts), while the opposite would be true of species falling on the opposite end of that continuum (Fig. 1). The interactive effect of these two processes may independently (or semi-independently) shape the grouping preferences of territorial individuals— such as prairie voles and territorial estrildids—to be socially averse to most but socially attracted to a few. Meanwhile this interconnected network of social processing neural structures may also shape the behavior of monogamous gregarious individuals such as zebra finches to be socially prone to many, with special affinity for social/mating partners. On the other hand, nonmonogamous mating strategies should generally encourage social indiscrimination and social seeking, because mating opportunity should increase as a function of social interaction. While male aggression may be expected when sexual selection is strong, male territorial behavior may be relaxed when fitness is less dependent on male resource holding potential and more dependent on maximizing courtship and mating events with territorial females. Meadow voles appear to fit the latter condition. (This highlights an ancillary point: behavioral and neural sex differences should be expected.) The “social grouping axis” may therefore be driven by the BSTm-LS peptide system, with territorial animals demonstrating low OTR, V1aR and nonapeptide levels and gregarious animals exhibiting comparably high OTR, V1aR and nonapeptide levels. Flocking and overwintering behavior of zebra finches and meadow voles may be on one extreme of this continuum; territoriality in other finches and prairie voles might be best placed together on the other. Ultimately, different patterns of valences associated with general social preferences will be determined by the “social grouping axis” and should determine the extent to which animals prefer to live in large or small groups. A specialized form of social discrimination should be expected among monogamous species, when compared to non-monogamous ones. The second axis may be best characterized by the intimate link between social selectivity and mating system, in which the mechanisms governing bonding drive selectivity. V1aR antagonist in the LS eliminates partner preferences in prairie voles, but prairie voles have relatively low V1aR expression compared to non-bonding voles. Social
A.G. Ophir / Hormones and Behavior 60 (2011) 22–27
25
Fig. 1. Social grouping preferences (x-axis) and mating system (y-axis) can be viewed as independent but interacting variables that shape the general social behavior of animals. Mechanisms associated with social grouping (x-axis) are briefly summarized in the figure (and more extensively in the text). Mechanisms associated with bonding (y-axis) include nonapeptides and catecholamines involved in social recognition and reward (see text and references therein). Dashed arrows represent how an interaction between the two axes might produce differences is social selectivity based on anxiety reactions (anxious or repose) to large social groups.
recognition disruption has been suggested as a possible explanation for this result (Young et al., 2005). However, thinking about the LS as a social grouping mediator provides a new hypothesis for why antagonist eliminated bonding: blocking V1aR function could push animals to become so anti-social that bonds are impossible. It remains to be tested whether the mechanisms driving this hypothesized selective discrimination relate to the reward structures involved in the “pairbond neural circuit,” mechanisms governing recognition, shared structures of the social brain, or some other combination of neural mechanisms. Social behavioral titration through anxiety? The mechanisms that modulate anxiety may be one fruitful area to search for answers. Much of this type of work has suggested that social stimuli alter HPA axis activity, which in turn influences the formation of social preferences. Indeed, stress responses modulate and are modulated by peptide hormones, and may color the social context. Territorial animals are presumably socially averse by nature, and it seems reasonable to assume that social interaction could promote anxiety among this type of individual (Fig. 1, dashed lines). For example, male prairie voles show elevated corticosterone concentrations when housed in mixed-sex pairs or same-sex or mixed-sex groups (Klein et al., 1997). Gregarious individuals should fall on the other extreme in which social interaction should not promote anxiety. Mating system, however, would be expected to shape the form of social anxiety or social comfort exhibited by different species (Fig. 1). The context set up by natural stress-responses to social conditions, and the mechanisms therein, could promote selective bonding among monogamous individuals that are normally socially averse. Hormones related to anxiety have been implicated in prairie vole pairbonding and prairie voles have peculiar and abnormally high baseline levels of corticosterone suggesting a naturally overactive HPA axis (De Vries,
2002; Lim et al., 2006, 2007). Furthermore, as discussed by Kelly et al., (2011) vasopressin is an anxiogenic for many rodents including prairie voles. Taken together, these mechanisms may promote selective bonding through social anxiety. For instance, territorial monogamous species such as prairie voles appear to be socially averse in a general sense (i.e., HPA axis activated when placed in groups), but stress responses could drive specific bonding in contexts where bonding is possible (i.e., mixed-sex pairs or groups). On the other hand, it is possible that the stress-mediated social context could facilitate grouping behavior in generally social animals by placing individuals at ease in social contexts. For example, Kelly et al. (2011) demonstrated that VT acts as an anxiolytic in zebra finches, potentially reducing social anxiety. The anxio-social context may therefore predispose monogamous individuals to form unique mate bonds while also promoting grouping behavior. In other cases, stress responses among non-monogamous individuals may have little or no effect on selective social preferences. In meadow voles, for example, males housed alone, in same-sex pairs, mixed-sex pairs, same-sex groups or mixed-sex groups show consistently low serum corticosterone concentrations (Klein et al., 1997) indicating a lack of stress response to various social contexts. Although males are non-territorial, female territoriality likely restricts species grouping (Madison, 1980). Genetic manipulation can be used to introduce the mechanisms necessary to form selective bonds in males, and in this case males do indeed form selective bonds (Lim et al., 2004). Whether such a manipulation would affect general social attraction among males—essentially shifting them to be more similar to zebra finches—remains an untested question. Nevertheless, this framework suggests that the modulatory influences of the stress response-peptide interaction may alter the social context sufficiently so, such that animals that vary along two orthogonal axes— namely mating system and social grouping—fit into relatively independent and distinct behavioral categories.
26
A.G. Ophir / Hormones and Behavior 60 (2011) 22–27
Other promising model systems: peromyscus It should go without saying that much of what has been discussed here is speculative, and that experimental tests are required to determine the validity of the hypotheses outlined above. The two model systems discussed above are good places to begin. A third system that could be very promising is that of Peromyscus rodents. Like prairie, pine, meadow and montane voles, Peromyscus species vary in mating system: P. californicus is sexually monogamous, P. polianotus appears to demonstrate obligate monogamy, P. maniculatus and P. leucopus vary from facultative monogamy to promiscuity, and P. melanophrys is probably polygynous (Wolff, 1989). While almost nothing is known about the oxytocin-OTR system of Peromyscus, some interesting incongruities in the vasopressin-V1aR profiles exist with regard to the framework proposed above. For example, P. californicus has more vasopressin in the BST and more V1aR in the LS than P. leucopus (BesterMeredith et al., 1999; Insel et al., 1991). Although the sample sizes were rather low, (N = 2 male and N = 2 female per species), Turner et al. (2010) showed that V1aR expression across eight Peromyscus species does not appear to predict the mating system or social grouping preferences. Monogamy has evolved multiply within this clade and whether this incongruence is due to fundamental differences between sexual monogamy (P. californicus), obligate monogamy (P. polionotus and P. eremicus) and facultative monogamy (P. maniculatus and P. leucopus), or the relationship between aggressive behavior and social spacing (c.f., Goodson and Bass, 2001) remains to be determined. Although on first glance the Peromyscus system appears to refute the hypotheses outlined in the current commentary, it may provide a profound opportunity to more fully explore the interaction between mating system and social grouping because some Peromyscus species appear to demonstrate great plasticity in each behavioral domain. For example, the social grouping tendencies for many of the species described by Turner et al. (2010) varies by season and by social density; differential day light conditions and/or social density can shift the mating system and the social grouping tendencies (e.g., Kleiman, 1977; Mineau and Madison, 1977; Wolff, 1989). Thus, maintaining animals under long days or at low densities may induce septal up- or downregulation of V1aR differentially across the clade, and could account for some of the intriguing results presented in Turner et al. (2010).
Tinbergen's challenge Tinbergen pushed the scientific community to gain a deeper understanding of behavior by combining efforts to explore behavior from multiple vantage points. Indeed, he emphasized that behavior of the whole animal cannot be fully understood unless we consider the multifaceted nature of behavior. In this view, the best way to understand the mechanisms that mediate decisions and influence behavior is to consider the ultimate functions of behavior. The best way to understand how adaptations evolve and are constrained from evolving is to appreciate the proximate substrates that govern behavior. Each answer is better informed by asking questions at different levels of analysis. By investigating the genetic and physiological mechanisms that shape individual behavior over the backdrop of comparing neural phenotypes across species, Kelly et al. (2011) provides an excellent example of Tinbergen's vision. In a call to arms, he wrote “I should like to emphasize that future work [on understanding the neurobiology of behavior] could only be done by workers who are fully acquainted with the instinctive behaviour as a whole and with its analysis, and at the same time are in command of neurophysiological methods and techniques. … Our science is suffering from a serious lack of students with these qualifications, and it is an urgent task of ethologists and neurophysiologists to join efforts in the training of ‘etho-physiologists’.” (Tinbergen, 1951). The work presented in Kelly et al. (2011) broadens our understanding of the mechanisms of social behavior, provokes a
reconsideration of traditionally conceived ideas of sociality, and represents a significant step toward meeting Tinbergen's challenge.
References Bamshad, M., Novak, M.A., DeVries, G.J., 1993. Sex and species differences in the vasopressin innervation of sexually naïve and parental prairie voles, Microtus ochrogaster and meadow voles. Microtus pennsylvanicus. J. Neuroendocrinol. 5, 247–255. Beery, A.K., Routman, D.M., Zucker, I., 2009. Same-sex social behavior in meadow voles: multiple and rapid formation of attachments. Physiol. Behav. 97, 52–57. Bester-Meredith, J.K., Young, L.J., Marler, C.A., 1999. Species differences in paternal behavior and aggression in Peromyscus and their associations with vasopressin immunoreactivity and receptors. Horm. Behav. 36, 25–38. Carter, C.S., DeVries, A.C., Getz, L.L., 1995. Physiological substrates of mammalian monogamy: the prairie vole model. Neurosci. Biobehav. Rev. 19, 303–314. Cho, M.M., DeVries, A.C., Williams, J.R., Carter, C.S., 1999. The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). Behav. Neurosci. 113, 1071–1079. De Vries, A.C., 2002. Interaction among social enviornment, the hypothalamic– pituitary–adrenal axis, and behavior. Horm. Behav. 41, 405–413. DeCoursey, G.E., 1957. Identification, ecology and reproduction of Microtus in Ohio. J. Mammal. 38, 44–52. Findley, J.S., 1951. Habitat preferences of four species of Microtus in Jackson Hole, Wyoming. J. Mammalogy 32, 118–120. Getz, L.L., Hofmann, J.E., 1986. Social organization in free-living prairie voles, Microtus ochrogaster. Behav. Ecol. Sociobiol. 18, 275–282. Getz, L.L., Carter, C.S., Gavish, L., 1981. The mating system by the prairie vole, Microtus ochrogaster. Behav. Ecol. Sociobiol. 8, 189–194. Getz, L.L., McGuire, B., Pizzuto, T., Hofmann, J., Frase, B., 1993. Social organization of the prairie vole (Microtus ochrogaster). J. Mammal. 74, 44–58. Goodson, J.L., 2005. The vertebrate social behavior network: evolutionary themes and variations. Horm. Behav. 48, 11–22. Goodson, J.L., 2008. Nonapeptides and the evolutionary patterning of sociality. Prog. Brain Res. 170, 3–15. Goodson, J.L., Bass, A.H., 2001. Social behavior functions and related anatomical characteristics of vasotocin/vasopressin systems in vertebrates. Brain Res. Rev. 35, 246–265. Goodson, J.L., Evans, A.K., Wang, Y., 2006. Neuropeptide bidning reflects convergent and divergent evolution in species-typical group sizes. Horm. Behav. 50, 223–236. Goodson, J.L., Rinaldi, J., Kelly, A.M., 2009a. Vasotocin neurons in the bed nucleus of the stria terminalis preferntially process social information and exhibit properties that dichotomize sourting and non-courting phenotypes. Horm. Behav. 55, 197–202. Goodson, J.L., Schrock, S.E., Klatt, J.D., Kabelik, D., Kingsbury, M.A., 2009b. Mesotocin and nonapeptide receptors promote estrildid flocking behavior. Science 325, 862–866. Goodson, J.L., Wang, Y., 2006. Valence-sensitive neurons exhibit divergent functional profiles in gregarious and asoical species. Proc. Nat'l. Acad. Sci. USA 103, 17013–17017. Gruder-Adams, S., Getz, L.L., 1985. Comparison of the mating system and paternal behavior in Microtus ochrogaster and M. pennsylvanicus. J. Mammal. 66, 165–167. Hebb, D.O., 1949. The Organisation of Behaviour. Wiley-Interscience, New York. Insel, T.R., Gelhard, R., Shapiro, L.E., 1991. The comparative distribution of forebrain receptors for neurohypophyseal peptides in monogamous and polygamous mice. Neuroscience 43, 623–630. Insel, T.R., Preston, S., Winslow, J.T., 1995. Mating in the monogamous male: behavioral consequences. Physiol. Behav. 57, 615–627. Insel, T.R., Shapiro, L.E., 1992. Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proc. Nat'l. Acad. Sci. USA 89, 5981–5985. Insel, T.R., Wang, Z.X., Ferris, C.F., 1994. Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents. J. Neurosci. 14, 5381–5392. Insel, T.R., Young, L.J., 2001. The neurobiology of attachment. Nat. Rev. Neurosci. 2, 129–136. Jacquot, J.J., Solomon, N.G., 2004. Experimental manipulation of territory occupancy: effects on immigration of female prairie voles. J. Mammal. 85, 1009–1014. Kelly, A.M., Kingsbury, M.A., Hoffbuhr, K., Schrock, S.E., Waxman, B., Kabelik, D., Thompson, R.R., Goodson, J.L., 2011. Vasotocin neurons and septal V1a-like receptors potently modulate songbird flocking and responses to novelty. Horm. Behav. 60, 12–21. Kennedy, J.S., 1992. The New Antrhopomorphism. Cambridge University Press, Cambridge. Kleiman, D.G., 1977. Monogamy In Mammals. Q. Rev. Biol. 52, 39–69. Klein, S.L., Hairston, J.E., De Vries, A.C., Nelson, R.J., 1997. Social enviornment and steroid hormones affect species and sex differences in immune function among voles. Horm. Behav. 32, 30–39. Krebs, J.R., Davies, N.B., 1997. Behavioural Ecology. Blackwell, Oxford. Lim, M.M., Tsivkovskaia, N.O., Bai, Y., Young, L.J., Ryabinin, A.E., 2006. Distribution of corticotropin-releasing factor and urocortin 1 in the vole brain. Brain Behav. Evol. 68, 229–240. Lim, M.M., Liu, Y., Ryabinin, A.E., Bai, Y., Wang, Z., Young, L.J., 2007. CRF receptors in the nucleus accumbens modulate partner preference in prairie voles. Horm. Behav. 51, 508–515.
A.G. Ophir / Hormones and Behavior 60 (2011) 22–27 Lim, M.M., Wang, Z.X., Olazabal, D.E., Ren, X.H., Terwilliger, E.F., Young, L.J., 2004. Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 429, 754–757. Lim, M.M., Young, L.J., 2004. Vasopressin-dependent neural circuits underlying pair bond formation in the monogamous prairie vole. Neuroscience 125, 35–45. Liu, Y., Curtis, J.T., Wang, Z.X., 2001. Vasopressin in the lateral septum regulates pair bond formation in male prairie voles (Microtus ochrogaster). Behav. Neurosci. 115, 910–919. Madison, D.M., 1980. Space use and social structure in meadow voles, Microtus pennsylvanicus. Behav. Ecol. Sociobiol. 7, 65–71. Madison, D.M., FitzGerald, R.W., McShea, W.J., 1984. Dynamics of social nesting in overwintering meadow voles (Microtus pennsylvanicus): possible consequences for population cycling. Behav. Ecol. Sociobiol. 15, 9–17. Mayr, E., 1961. Cause and effect in biology. Science 134, 1501–1506. Mineau, P., Madison, D., 1977. Radiotracking of Peromyscus leucopus. Can. J. Zool. 55, 465–468. Newman, S.W., 1999. The medial extended amygdala in male reproductive behavior: a node in the mammalian social behavior network. Ann. N.Y. Acad. Sci. 877, 242–257. Swanson, L.W., 2000. Cerebral hemisphere regulation of motivated behavior. Brain Res. 886, 113–164. Thierry, B., 2005. Integrating proximate and ultimate causation: just one more go! Curr. Sci. 89, 1180–1183. Thomas, J.A., Birney, E.C., 1979. Parental care and mating system of the prairie vole, Microtus ochrogaster. Behav. Ecol. Sociobiol. 5, 171–186. Tinbergen, N., 1951. The Study of Instinct. Oxford University Press, New York. Tinbergen, N., 1963. On aims and methods in ethology. Z. Tierpsychol. 20, 410–433. Turner, L.M., Young, A.Y., Rompler, H., Schoneberg, T., Phelps, S.M., Hoekstra, H.E., 2010. Monogamy evolves through multiple mechanisms: evidence from V1aR in deer mice. Mol. Biol. Evol. 27, 1269–1278.
27
Wang, Z., 1995. Species differences in the vasopressin-immunoreactive pathways in the bed nucleus of the stria terminalis and medial amygdaloid nucleus in prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus). Behav. Neurosci. 109, 305–311. Wang, Z.X., Smith, W., Major, D.E., DeVries, G.J., 1994. Sex and species differences in the effects of cohabitation on vasopressin messenger RNA expression in the bed nucleus of the stria terminalis in prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus). Brain Res. 650, 212–218. Wang, Z.X., Young, L.J., De Vries, G.J., Insel, T.R., 1998. Voles and vasopressin: a review of molecular, cellular, and behavioral studies of pair bonding and paternal behaviors. Advan. Brain Vasopressin 483–499. Webster, A.B., Brooks, R.J., 1981. Social behavior of Microtus pennsylvanicus in relation to seasonal changes in demography. J. Mammal. 62, 738–751. Williams, G.C., 1966. Adaptation and Natural Selection. Princeton University Press, Princeton. Williams, J.R., Insel, T.R., Harbaugh, C.R., Carter, C.S., 1994. Oxytocin administered centrally facilitates formation of a partner preference in female prairie voles. J. Neuroendocrinol. 6, 247–250. Winslow, J.T., Hastings, N., Carter, C.S., Harbaugh, C.R., Insel, T.R., 1993. A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365, 545–548. Wolff, J.O., 1989. Social Behavior. Advances in the Study of Peromyscus (Rodentia). Texase Tech University Press, Lubbock. Young, L.J., Wang, Z.X., 2004. The neurobiology of pair bonding. Nat. Neurosci. 7, 1048–1054. Young, L.J., Winslow, J.T., Nilsen, R., Insel, T.R., 1997. Species differences in V1a receptor gene expression in monogamous and nonmonogamous voles: behavioral consequences. Behav. Neurosci. 111, 599–605. Young, L.J., Young, A.Z.M., Hammock, E.A.D., 2005. Anatomy and neurochemistry of the pair bond. J. Comp. Neurol. 493, 51–57.