Claudia Lieberwirth

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 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.

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).

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.

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).

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

Abstract 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.

SCATTER HOARDING AND HIPPOCAMPAL CELL PROLIFERATION IN SIBERIAN CHIPMUNKS

Food hoarding, especially scatter hoarding and retrieving food caches, requires spatial learning and memory and is an adaptive behavior important for an animals survival and reproductive success. In the present study, we examined the effects of hoarding behavior on cell proliferation and survival in the hippocampus of male and female Siberian chipmunks (Tamias sibiricus). We found that chipmunks in a semi-natural enclosure displayed hoarding behavior with large individual variations. Males ate more scatter-hoarded seeds than females. In addition, the display of hoarding behavior was associated with increased cell proliferation in the hippocampus and this increase occurred in a brain region-specific manner. These data provide further evidence to support the notion that new cells in the adult hippocampus are affected by learning and memory tasks and may play an important role in adaptive behavior.

Chemosensory cues affect amygdaloid neurogenesis and alter behaviors in the socially monogamous prairie vole

The current study examined the effects of pheromonal exposure on adult neurogenesis and revealed the role of the olfactory pathways on adult neurogenesis and behavior in the socially monogamous prairie vole (Microtus ochrogaster). Subjects were injected with a cell proliferation marker [5‐bromo‐2′‐deoxyuridine (BrdU)] and then exposed to their own soiled bedding or bedding soiled by a same‐ or opposite‐sex conspecific. Exposure to opposite‐sex bedding increased BrdU labeling in the amygdala (AMY), but not the dentate gyrus (DG), of female, but not male, voles, indicating a sex‐, stimulus‐, and brain region‐specific effect. The removal of the main olfactory bulbs or lesioning of the vomeronasal organ (VNOX) in females reduced BrdU labeling in the AMY and DG, and inhibited the male bedding‐induced BrdU labeling in the AMY, revealing the importance of an intact olfactory pathway for amygdaloid neurogenesis. VNOX increased anxiety‐like behavior and altered social preference, but it did not affect social recognition memory in female voles. VNOX also reduced the percentage of BrdU‐labeled cells that co‐expressed the neuronal marker TuJ1 in the AMY, but not the DG. Together, our data indicate the importance of the olfactory pathway in mediating brain plasticity in the limbic system as well as its role in behavior.

Social defeat and subsequent isolation housing affect behavior as well as cell proliferation and cell survival in the brains of male greater long-tailed hamsters

Aversive social interactions, such as social defeat, can alter a variety of behavioral and cognitive functions. In the present study, we examined the effects of social defeat and the subsequent housing on behavior as well as cell proliferation and cell survival in the solitary, male greater long-tailed hamster (Tscheskia triton). We found that three days of agonistic interactions reliably led to a subordinate-dominant relationship between pairs of male hamsters. However, such behavioral interactions did not alter cell proliferation in any of the brain areas examined. In addition, subordinate males housed in close proximity to the dominant male (separated by a wire screen) following social defeat did not display differences in agonistic behaviors, but had enhanced cell proliferation in the anterior hypothalamus, ventromedial hypothalamus (VMH), and amygdala as well as increased cell survival in the VMH, compared to subordinate males that were housed individually. Together, our data indicate distinct effects of agonistic interactions and the social housing condition on behavior as well as cell proliferation and survival in the brain of the greater long-tailed hamster.

Species differences in behavior and cell proliferation/survival in the adult brains of female meadow and prairie voles

Microtine rodents display diverse patterns of social organization and behaviors, and thus provide a useful model for studying the effects of the social environment on physiology and behavior. The current study compared the species differences and the effects of oxytocin (OT) on anxiety-like, social affiliation, and social recognition behaviors in female meadow voles (Microtus pennsylvanicus) and prairie voles (Microtus ochrogaster). Furthermore, cell proliferation and survival in the brains of adult female meadow and prairie voles were compared. We found that female meadow voles displayed a higher level of anxiety-like behavior but lower levels of social affiliation and social recognition compared to female prairie voles. In addition, meadow voles showed lower levels of cell proliferation (measured by Ki67 staining) and cell survival (measured by BrdU staining) in the ventromedial hypothalamus (VMH) and amygdala (AMY), but not the dentate gyrus of the hippocampus (DG), than prairie voles. Interestingly, the numbers of new cells in the VMH and AMY, but not DG, also correlated with anxiety-like, social affiliation, and social recognition behaviors in a brain region-specific manner. Finally, central OT treatment (200 ng/kg, icv) did not lead to changes in behavior or cell proliferation/survival in the brain. Together, these data indicate a potential role of cell proliferation/survival in selected brain areas on different behaviors between vole species with distinct life strategies.