Male prairie voles (Microtus ochrogaster) display mating-induced pair bonding indicated by social affiliation with their female partners and aggression toward unfamiliar conspecifics. In the present study, we characterized their aggression associated with pair bonding and examined the related neuronal activation and neurochemical architecture. Males that were pair-bonded for 2 weeks displayed intense levels of aggression toward a female or male conspecific stranger but maintained a high level of social affiliation with their familiar female partners. These social interactions induced increases in neural activation, indicated by increased density of Fos-immunoreactive staining (Fos-ir) in several brain regions including the bed nucleus of the stria terminalis (BNST), medial preoptic area (MPOA), paraventricular nucleus (PVN), anterior cortical (AcA), and medial nuclei (MeA) of the amygdala. In the anterior hypothalamus (AH), increased density of Fos-ir staining was found specifically to be associated with aggression toward unfamiliar female or male strangers. In addition, higher densities of AH cells that were stained for tyrosine hydroxylase (TH) or vasopressin (AVP) were also labeled with Fos-ir in these males displaying aggression toward a conspecific stranger compared with males displaying social affiliation toward their female partner. Together, our results indicate that dopamine and vasopressin in the AH may be involved in the regulation of enduring aggression associated with pair bonding in male 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.

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.

Background The neuropeptides vasopressin (AVP) and corticotrophin-releasing hormone (CRH) facilitate while serotonin (5-HT) inhibits aggression. How the brain is wired to coordinate interactions between these functionally opposed neurotransmitters to control behavioral states is poorly understood. Methods Pair-bonded male prairie voles (Microtus ochrogaster) were infused with a retrograde tracer, fluorogold, and tested for affiliation and aggression toward a female partner or novel female. Subsequent immunocytochemical experiments examined neuronal activation using FOS and neuro-chemical/-receptor profiles on brain areas involved in the behaviors. Finally, a series of behavioral pharmacological and real-time in-vivo brain microdialysis experiments were performed on male prairie voles displaying affiliation or aggression. Results We localized a subpopulation of excitatory AVP neurons in the anterior hypothalamic nucleus (AH) that may gate CRH output from the amygdala to the AH and then the lateral septum to modulate aggression associated with mate guarding. Conversely, we identified a subset of inhibitory 5-HT-ergic projection neurons in the dorsal raphe nucleus to the AH that mediates the spatio-temporal release of neuropeptides and their interactions in modulating aggression and affiliation. Conclusions Together, this study establishes the medial extended amygdala as a major neural substrate regulating the switch between positive and negative affective states wherein several neurochemicals converge and interact to coordinate divergent social behaviors.

Background: Circadian rhythm disturbance is common postoperatively in older patients with hip fractures, which may contribute to the development of postoperative delirium (POD). As a reliable biomarker of endogenous circadian rhythms, melatonin regulates the sleep-wake cycle and environmental adaptation, and its secretory rhythm may be modified by anaesthesia and surgery. This study compared the impact of subarachnoid anaesthesia (SA) and general anaesthesia (GA), on the peak of melatonin secretion (primary outcome), the circadian rhythm of melatonin, cortisol and sleep, and the POD incidence (secondary outcome). Methods: In this prospective cohort observational study, hip fracture surgery patients were enrolled and assigned to receive either SA or GA. Postoperative plasma melatonin and cortisol levels were dynamically measured every six hours on seven time-points, and the circadian rhythm parameters including mesor, amplitude, and acrophase were calculated. Subjective and objective sleep assessments were performed by sleep diaries and sleep trackers, respectively. The Confusion Assessment Method was used twice daily by a specific geriatrician to screen for POD occurrence. Findings: In a cohort of 138 patients who underwent hip fracture surgery, the circadian rhythm disruption of the patients in the GA group (n=69) was greater than the SA group (n=69). Compared with SA, GA provided the lower peak concentration, mesor, and amplitude of melatonin secretion on postoperative day 1 (p < 0.05). Patients in the GA group experienced higher awakenings, more sleep deprivation, and poor sleep quality on surgery day (p < 0.05). A proportion of 12 patients in the SA group (17.4%) and 24 patients in the GA group (34.8%) experienced POD (p = 0.020). Interpretation: These results suggest that SA may be superior to GA in elderly patients undergoing hip fracture surgery as SA is associated with less impairment of the melatonin rhythm and sleep patterns, and fewer POD occurrences.