Chapter 16 Neural Regulation of Social Behavior in Rodents J. Thomas Curtis, Yan Liu, Brandon J. Aragona, and Zuoxin Wang ocial behavior arises from a complex interplay since behaviors such as aggression likely derive from the of numerous and often-competing sensory stimuli, the mating system. S physiological and motivational states of the partici- Rodents are a diverse group of creatures that inhabit a pants, and the ages and genders of the individuals involved. wide variety of ecological niches. As might be expected of Overlying the internal responses to a social encounter are such diversity, rodents display a wide range of mating sys- a variety of external factors, such as the context in which tems. Males and females of many species often have differ- the encounter occurs, the time of year, environmental con- ent mating strategies (Waterman, chap. 3, Solomon and ditions, and the outcomes of previous social interactions. Keane, chap. 4, this volume). However, some environmental To further complicate the situation, each individual in a so- conditions require extensive cooperation between the sexes cial encounter must be able to adjust its own actions de- for reproductive success (Kleiman 1977). In these cases, the pending on the responses of other animals. Given such com- mating strategies of the two sexes may converge and a plexity, a detailed understanding of the neural basis of social monogamous mating system may arise. Only about 3% of behavior would seem next to impossible. Nonetheless, con- mammalian species have been categorized as being monog- siderable progress has been made. By examining individual amous (Kleiman 1977). Within the rodent order, monog- components of social behavior while controlling for other amy has arisen several times (Kleiman 1977), in some cases variables, researchers have begun to parcel out the contri- within genera in which other species are not monogamous. butions of specific brain regions and neurochemicals to spe- This polyphyletic origin to mating systems has presented cific aspects of social behavior. opportunities for detailed comparative studies of the neural A comprehensive survey of the hormonal and neural con- control of social behaviors and how the brains differ be- trol of all of the different types of rodent social behavior is tween closely related species with different social structures. beyond the scope of a single book chapter. Here, we will concentrate on the neuroanatomical and neurochemical substrates that underlie rodent social structures, with a par- Comparative Models ticular focus on social bonds. Behavior, like all other aspects of a species’ natural history, is subject to natural selection. Over the past two decades much research on social behav- Since the ultimate test of a behavioral repertoire is repro- ior has focused on two genera: Microtus and Peromyscus. ductive success, it is perhaps appropriate to focus on mat- Species within Microtus or Peromyscus often display very ing systems in addressing the neural control of social behav- similar nonsocial behaviors, such as activity and feeding ior. By focusing on mating systems we are able to place a patterns (Madison 1985), but differ significantly in social variety of social behaviors into a firm ecological context, interactions and mating systems (Dewsbury 1987; Bester- 186 Chapter Sixteen Meredith et al. 1999). Most species exhibit a promiscuous Behavioral differences reflecting the various social struc- mating system. Promiscuous species show little in the way tures also are reflected to some extent in the play behavior of social ties, typically defend individual territories, and the of juvenile rodents (Pellis et al. 1989). This is not surpris- female usually is the sole caretaker of pups. A few spe- ing, since juvenile play behavior may serve to prepare rele- cies, however, display characteristics of monogamy such as vant brain circuitry for appropriate adult social behavior shared parental care, shared nests even beyond the breeding (Cooke et al. 2000). In fact, rats (Rattus norvegicus) that season, and selective aggression against strangers but not are deprived of opportunities to engage in play when young toward the partner. These animals form strong pair bonds display deficits in social behavior as adults (van den Berg with their mate, which are manifested by a preference for et al. 1999). Young prairie voles, which are highly social as social contact with the partner even when other conspecif- adults, display a greater propensity for intimate contact and ics are available. mutual grooming than do young meadow voles, which are Such species differences in social behavior have been ex- rather asocial as adults (Wilson 1982a). Juveniles of highly ploited in comparative studies that allow differences in so- social vole species also exhibit more complex play behavior cial organization to be correlated with neuroanatomical (Pellis and Iwaniuk 1999), and the structure of play differs and neurochemical differences between species. Similarities from that of asocial species (Pellis et al. 1989; Pierce et al. in nonsocial behaviors suggest that differences found in the 1991). In play fighting, a passive defense posture is adopted brain are more likely to be related to social behavior. Stud- by social species, while a more aggressive defense posture ies using Peromyscus and Microtus have identified a number is adopted by nonsocial species (Pellis et al. 1989). Interest- of brain regions and neurochemical systems that are criti- ingly, the differences in play appear to reflect differences in cally involved in the central control of socially relevant be- precopulatory behavioral patterns of adults of each species haviors but that differ between species with differing mat- (Pellis et al. 1989; Pierce et al. 1991). ing systems. Although we will concentrate on these genera, The differences in juvenile behaviors suggest that there we are in no way minimizing the contributions arising from are differences in the central nervous system early in de- studies using other rodent species. In many cases, work on velopment among rodents with differing social systems. In- rats, hamsters, and other species of mice (numerous strains deed, several studies have shown that brain development derived from Mus musculus) has laid the groundwork for may be delayed in monogamous voles. Allometric relation- studies in Peromyscus and Microtus, and we will refer often ships are ratios between pairs of measures of an animal, and to such work to provide context for findings in these latter these ratios may change during development. Vole species species. with differing mating systems display different allometric relationships between brain mass and body mass during de- velopment. Promiscuous vole species switch from an im- Research in Juveniles mature allometric growth pattern to an adult pattern earlier in development than do the monogamous voles (Gutierrez Species differences associated with social behavior arise et al. 1989), suggesting that brain development is delayed early in development, even among closely related species. In in monogamous voles. These species differences in brain general, pups of promiscuous species such as the meadow growth may be attributable to the proliferation of new cells. voles (M. pennsylvanicus) and montane voles (M. mon- Indices of cell proliferation in the cerebrum suggest that tanus) show more rapid development when compared to the brains of monogamous pine voles are still undergoing pups from monogamous pine voles (M. pinetorum) and considerable mitotic activity at 5 days postnatally. At the prairie voles (M. ochrogaster) (McGuire and Novak 1984; same age, however, mitotic activity is significantly reduced Nadeau 1985; McGuire and Novak 1986; Prohazka et al. in meadow voles and in other non-pair-bonding species 1986). Relative to monogamous species, promiscuous vole such as rats and mice (Gutierrez et al. 1989). In the same species display more advanced neuromuscular development study, monogamous vole species were also found to display at five days of age, and become independent earlier. Pups a greater increase in cell proliferation in the cerebellum be- from promiscuous vole species eat solid food as early as tween 2 and 5 days of age compared to that in promiscuous 8 days of age and wean at 13–14 days, while pups of mo- voles, again suggesting that brain development is delayed in nogamous vole species are not weaned until about 1 week monogamous species. This difference may account for the later (McGuire and Novak 1984). Similarly, among Pero- more advanced neuromuscular development displayed by myscus, pups of a promiscuous species, the white-footed promiscuous vole pups (Prohazka et al. 1986). mouse (P. leucopus), open their eyes earlier and wean ear- In addition to differences in brain growth, the develop- lier than do pups of monogamous California mice (P. cali- ment of neurochemical systems differs between species with fornicus) ( reviewed by Layne [1968]). differing social systems. For example, brain derived neu- Neural Regulation of Social Behavior in Rodents 187 rotrophic factor (BDNF) is important for the proliferation of neurons as well as for their survival and growth. In some brain areas the promiscuous meadow vole displays adult patterns of BDNF expression at about 2 weeks of age, while the monogamous prairie vole does not show adult patterns until at least 3 weeks of age (Liu, Fowler et al. 2001). It is interesting to note that the timing of the switch to adult pat- terns of BDNF expression to some extent parallels the tim- ing of weaning and independence in each species. Monog- amous prairie voles and promiscuous montane voles also differ in temporal and regional expression of the gene for receptors that bind the neurochemicals vasopressin or oxy- tocin (Wang and Young 1997; Wang, Young et al. 1997), which, in adults, are critical for social memory and/or for the formation of social attachments in monogamous spe- cies (Dantzer et al. 1988; Williams et al. 1994; Wang et al. 1998). Collectively, these observations demonstrate clear spe- cies differences in the ontogeny of the brain that may be im- portant for species-specific social structures.