The neurobiology of pair bond formation, bond disruption, and social buffering.

Enduring social bonds play an essential role in human society. These bonds positively affect psychological, physiological, and behavioral functions. Here, we review the recent literature on the neurobiology, particularly the role of oxytocin and dopamine, of pair bond formation, bond disruption, and social buffering effects on stress responses, from studies utilizing the socially monogamous prairie vole (Microtus ochrogaster).

Hippocampal adult neurogenesis: Its regulation and potential role in spatial learning and memory.

Adult neurogenesis, defined here as progenitor cell division generating functionally integrated neurons in the adult brain, occurs within the hippocampus of numerous mammalian species including humans. The present review details various endogenous (e.g., neurotransmitters) and environmental (e.g., physical exercise) factors that have been shown to influence hippocampal adult neurogenesis. In addition, the potential involvement of adult-generated neurons in naturally-occurring spatial learning behavior is discussed by summarizing the literature focusing on traditional animal models (e.g., rats and mice), non-traditional animal models (e.g., tree shrews), as well as natural populations (e.g., chickadees and Siberian chipmunk).

Social bonding: regulation by neuropeptides.

Affiliative social relationships (e.g., among spouses, family members, and friends) play an essential role in human society. These relationships affect psychological, physiological, and behavioral functions. As positive and enduring bonds are critical for the overall well-being of humans, it is not surprising that considerable effort has been made to study the neurobiological mechanisms that underlie social bonding behaviors. The present review details the involvement of the nonapeptides, oxytocin (OT), and arginine vasopressin (AVP), in the regulation of social bonding in mammals including humans. In particular, we will discuss the role of OT and AVP in the formation of social bonds between partners of a mating pair as well as between parents and their offspring. Furthermore, the role of OT and AVP in the formation of interpersonal bonding involving trust is also discussed.

Fatherhood reduces the survival of adult-generated cells and affects various types of behavior in the prairie vole (Microtus ochrogaster ).

Motherhood has profound effects on physiology, neuronal plasticity, and behavior. We conducted a series of experiments to test the hypothesis that fatherhood, similarly to motherhood, affects brain plasticity (such as cell proliferation and survival) and various behaviors in the highly social prairie vole (Microtus ochrogaster). In Experiment 1, adult males were housed with their same-sex cage mate (control), single-housed (isolation), or housed with a receptive female to mate and produce offspring (father) for 6 weeks. Fatherhood significantly reduced cell survival (assessed by bromodeoxyuridine labeling), but not cell proliferation (assessed by Ki67-labeling), in the amygdala, dentate gyrus of the hippocampus, and ventromedial hypothalamus, suggesting that fatherhood affects brain plasticity. In Experiment 2, neither acute (20 min) nor chronic (20 min daily for 10 consecutive days) pup exposure altered cell proliferation or survival in the brain, but chronic pup exposure increased circulating corticosterone levels. These data suggest that reduced cell survival in the brain of prairie vole fathers was unlikely to be due to the level of pup exposure and display of paternal behavior, and may not be mediated by circulating corticosterone. The effects of fatherhood on various behaviors (including anxiety-like, depression-like, and social behaviors) were examined in Experiment 3. The data indicated that fatherhood increased anxiety- and depression-like behaviors as well as altered aggression and social recognition memory in male prairie voles. These results warrant further investigation of a possible link between brain plasticity and behavioral changes observed due to fatherhood.

Behavioral and physiological responses of female prairie voles (Microtus ochrogaster) to various stressful conditions.

Stressful life events elicit hypothalamic-pituitary-adrenal (HPA) axis activation, which may alter psychological states or behavioral routines. Therefore, the current study focused on the HPA axis response to better understand such manifestations in female prairie voles (Microtus ochrogaster). In Experiment 1, females were stressed for 1 h via one of the four stressors: exposure to a novel environment, immobilization ("plastic mesh"), brief social defeat, or prolonged social defeat. Following a 30-min recovery, the females received a 5-min elevated plus maze (EPM) test and, subsequently, blood was collected to measure plasma corticosterone concentrations. Only immobilization stress induced an anxiety-like behavioral response in the EPM test and elevated plasma corticosterone levels compared to the control groups. Corticosterone concentrations were also significantly elevated following exposure to prolonged social defeat compared to the control conditions, but not after novel environment stress or short social defeat. In Experiment 2, females were exposed to immobilization stress over 1, 3, or 7 days in a daily (predictable; pIMO) or irregular (unpredictable; uIMO) schedule. The biobehavioral stress response in females exposed to pIMO for 3 or 7 days did not differ significantly from controls, suggesting these females habituated. By comparison, females exposed to uIMO over 3 or 7 days did not habituate behaviorally or physiologically, even producing augmented corticosterone levels. In both experiments, positive correlations were found between corticosterone levels and anxiety-like behaviors in the EPM test. Together, our data suggest that the stress response by female prairie voles is dependent on stress intensity, source, previous experience, and predictability. Furthermore, the HPA axis response, as evident by corticosterone levels, is associated with the impact that these factors have on behavioral routine.

The social environment and neurogenesis in the adult Mammalian brain.

Adult neurogenesis - the formation of new neurons in adulthood - has been shown to be modulated by a variety of endogenous (e.g., trophic factors, neurotransmitters, and hormones) as well as exogenous (e.g., physical activity and environmental complexity) factors. Research on exogenous regulators of adult neurogenesis has focused primarily on the non-social environment. More recently, however, evidence has emerged suggesting that the social environment can also affect adult neurogenesis. The present review details the effects of adult-adult (e.g., mating and chemosensory interactions) and adult-offspring (e.g., gestation, parenthood, and exposure to offspring) interactions on adult neurogenesis. In addition, the effects of a stressful social environment (e.g., lack of social support and dominant-subordinate interactions) on adult neurogenesis are reviewed. The underlying hormonal mechanisms and potential functional significance of adult-generated neurons in mediating social behaviors are also discussed.

Social isolation impairs adult neurogenesis in the limbic system and alters behaviors in female prairie voles.

Disruptions in the social environment, such as social isolation, are distressing and can induce various behavioral and neural changes in the distressed animal. We conducted a series of experiments to test the hypothesis that long-term social isolation affects brain plasticity and alters behavior in the highly social prairie vole (Microtus ochrogaster). In Experiment 1, adult female prairie voles were injected with a cell division marker, 5-bromo-2'-deoxyuridine (BrdU), and then same-sex pair-housed (control) or single-housed (isolation) for 6 weeks. Social isolation reduced cell proliferation, survival, and neuronal differentiation and altered cell death in the dentate gyrus of the hippocampus and the amygdala. In addition, social isolation reduced cell proliferation in the medial preoptic area and cell survival in the ventromedial hypothalamus. These data suggest that long-term social isolation affects distinct stages of adult neurogenesis in specific limbic brain regions. In Experiment 2, isolated females displayed higher levels of anxiety-like behaviors in both the open field and elevated plus maze tests and higher levels of depression-like behavior in the forced swim test than controls. Further, isolated females showed a higher level of affiliative behavior than controls, but the two groups did not differ in social recognition memory. Together, our data suggest that social isolation not only impairs cell proliferation, survival, and neuronal differentiation in limbic brain areas, but also alters anxiety-like, depression-like, and affiliative behaviors in adult female prairie voles. These data warrant further investigation of a possible link between altered neurogenesis within the limbic system and behavioral changes.