Aggression: Perspectives from social and systems neuroscience.

Exhibiting behavioral plasticity in order to mount appropriate responses to dynamic and novel social environments is crucial to the survival of all animals. Thus, how animals regulate flexibility in the timing, duration, and intensity of specific behaviors is of great interest to biologists. In this review, we discuss how animals rapidly respond to social challenges, with a particular focus on aggression. We utilize a conceptual framework to understand the neural mechanisms of aggression that is grounded in Wingfield and colleagues' Challenge Hypothesis, which has profoundly influenced how scientists think about aggression and the mechanisms that allow animals to exhibit flexible responses to social instability. Because aggressive behavior is rooted in social interactions, we propose that mechanisms modulating prosocial behavior may be intricately tied to mechanisms of aggression. Therefore, in order to better understand how aggressive behavior is mediated, we draw on perspectives from social neuroscience and discuss how social context, species-typical behavioral phenotype, and neural systems commonly studied in relation to prosocial behavior (i.e., neuropeptides) contribute to organizing rapid responses to social challenges. Because complex behaviors are not the result of one mechanism or a single neural system, we consider how multiple neural systems important for prosocial and aggressive behavior (i.e., neuropeptides and neurosteroids) interact in the brain to produce behavior in a rapid, context-appropriate manner. Applying a systems neuroscience perspective and seeking to understand how multiple systems functionally integrate to rapidly modulate behavior holds great promise for expanding our knowledge of the mechanisms underlying social behavioral plasticity.

Seasonal Variation in Group Size Is Related to Seasonal Variation in Neuropeptide Receptor Density.

In many species, seasonal variation in grouping behavior is widespread, with shifts towards territoriality in the breeding season and grouping in the winter. Compared to the hormonal and neural mechanisms of seasonal territorial aggression, the mechanisms that promote seasonal grouping have received little attention. We collected brains in spring and winter from wild-caught males of two species of emberizid sparrows that seasonally flock (the field sparrow, Spizella pusilla, and the dark-eyed junco, Junco hyemalis) and two species that do not seasonally flock (the song sparrow, Melospiza melodia, and the eastern towhee, Pipilo erythrophthalmus). We used receptor autoradiography to quantify seasonal plasticity in available binding sites for three neuropeptides known to influence social behavior. We examined binding sites for 125I-vasoactive intestinal polypeptide (VIP), 125I-sauvagine (SG, a ligand for corticotropin-releasing hormone receptors) and 125I-ornithine vasotocin analog (OVTA, a ligand for the VT3 nonapeptide). For all species and ligands, brain areas that exhibited a seasonal pattern in binding density were characterized by a winter increase. Compared to nonflocking species, seasonally flocking species showed different binding patterns in multiple brain areas. Furthermore, we found that winter flocking was associated with elevated winter 125I-VIP binding density in the medial amygdala, as well as 125I-VIP and 125I-OVTA binding density in the rostral arcopallium. While the functional significance of the avian rostral arcopallium is unclear, it may incorporate parts of the pallial amygdala. Our results point to this previously undescribed area as a likely hot spot of social modulation.

To flock or fight: neurochemical signatures of divergent life histories in sparrows.

Many bird species exhibit dramatic seasonal switches between territoriality and flocking, but whereas neuroendocrine mechanisms of territorial aggression have been extensively studied, those of seasonal flocking are unknown. We collected brains in spring and winter from male field sparrows (Spizella pusilla), which seasonally flock, and male song sparrows (Melospiza melodia), which are territorial year-round in much of their range. Spring collections were preceded by field-based assessments of aggression. Tissue series were immunofluorescently multilabeled for vasotocin, mesotocin (MT), corticotropin-releasing hormone (CRH), vasoactive intestinal polypeptide, tyrosine hydroxylase, and aromatase, and labeling densities were measured in many socially relevant brain areas. Extensive seasonal differences are shared by both species. Many measures correlate significantly with both individual and species differences in aggression, likely reflecting evolved mechanisms that differentiate the less aggressive field sparrow from the more aggressive song sparrow. Winter-specific species differences include a substantial increase of MT and CRH immunoreactivity in the dorsal lateral septum (LS) and medial amygdala of field sparrows but not song sparrows. These species differences likely relate to flocking rather than the suppression of winter aggression in field sparrows, because similar winter differences were found for two other emberizids that are not territorial in winter--dark-eyed juncos (Junco hyemalis), which seasonally flock, and eastern towhees (Pipilo erythropthalmus), which do not flock. MT signaling in the dorsal LS is also associated with year-round species differences in grouping in estrildid finches, suggesting that common mechanisms are targeted during the evolution of different life histories.

Heart and shoal: Social cues and oxytocin receptors impact stress recovery in the zebrafish.

In many species, social interactions decrease behavioral, hormonal, and neural responses to environmental stressors. While "social buffering" and its mechanisms have received considerable attention in mammals, we know less about the phenomenon in fish. The nonapeptide oxytocin regulates social behavior across vertebrates and plays an important role in social buffering in mammals. We investigated social buffering in the zebrafish by evaluating how the social environment and oxytocin receptors impact recovery from an acute stressor. Male and female fish were briefly exposed to alarm substance and recovered either in isolation or within view of a stimulus shoal. Alarm substance did not increase social approach, but social stimuli improved behavioral stress recovery. Oxytocin receptor antagonism decreased social approach during stress recovery and impaired stress recovery exclusively in individuals with access to visual social stimuli. Our findings contribute to the growing body of evidence that social stimuli buffer stress responses in fish and suggest that oxytocin receptors may play a role in socially-buffered stress recovery across taxa.

Neural responses to familiar conspecifics are modulated by a nonapeptide receptor in a winter flocking sparrow.

The social behavior network, a collection of reciprocally connected areas within the basal forebrain and midbrain, plays a conserved role in the regulation of vertebrate social behavior. Specific behaviors are associated with patterns of activity across the network, and these activity profiles vary with species and context. We investigated how the social behavior network responds to familiar social stimuli in a seasonally flocking songbird. Further, we explored how socially-induced neural responses are modulated by endogenous nonapeptide receptor blockade. Winter flocking dark-eyed juncos were exposed to either familiar conspecifics or a familiar empty aviary following a peripheral injection of either saline or [desGly-NH2,d(CH2)5, Tyr(Me)2,Thr4]-ornithine vasotocin, an VT3 receptor antagonist. Socially-exposed animals exhibited greater Fos induction across the social behavior network. Sex and drug effects were site-specific, with females tending to exhibit greater Fos responses to social stimuli and a greater sensitivity to VT3 antagonism. We suggest that in flocking animals, VT3 activation during social interaction may shift the pattern of neural activity towards the dorsocaudal lateral septum and rostral arcopallium and away from the extended amygdala, anterior and ventromedial hypothalamus, and the caudal ventral/ventrolateral lateral septum.

The Role of VIP in Social Behavior: Neural Hotspots for the Modulation of Affiliation, Aggression, and Parental Care.

Although the modulation of social behaviors by most major neurochemical systems has been explored, there are still standouts, including the study of vasoactive intestinal polypeptide (VIP). VIP is a modulator of circadian, reproductive, and seasonal rhythms and is well known for its role in reproductive behavior, as it is the main vertebrate prolactin-releasing hormone. Originally isolated as a gut peptide, VIP and its cognate receptors are present in virtually every brain area that is important for social behavior, including all nodes of the core "social behavior network" (SBN). Furthermore, VIP cells show increased transcriptional activity throughout the SBN in response to social stimuli. Using a combination of comparative and mechanistic approaches in socially diverse species of estrildid finches and emberizid sparrows, we have identified neural "hotspots" in the SBN that relate to avian affiliative behavior, as well as neural "hotspots" that may represent critical nodes underlying a trade-off between aggression and parental care. Specifically, we have found that: (1) VIP fiber densities and VIP receptor binding in specific brain sites, such as the lateral septum, medial extended amygdala, arcopallium, and medial nidopallium, correlate with species and/or seasonal differences in flocking behavior, and (2) VIP cells and fibers within the anterior hypothalamus-caudocentral septal circuit relate positively to aggression and negatively to parental care while VIP elements in the mediobasal hypothalamus relate negatively to aggression and positively to parental care. Thus, while a given behavior or social context likely activates VIP circuitry throughout the SBN and beyond, key brain sites emerge as potential "hotspots" for the modulation of affiliation, aggression, and parental care.

Cervical preparation for surgical abortion between 12 and 18 weeks of gestation using vaginal misoprostol and Dilapan-S.

BACKGROUND: We investigated the safety and efficacy of using misoprostol and Dilapan-S™ hygroscopic cervical dilators to prepare the cervix for surgical abortion from 12 to 18 weeks of gestation in an outpatient office setting. STUDY DESIGN: This retrospective cohort study evaluated 554 consecutive women who had a surgical abortion from 12 to 18 weeks of gestation using a cervical preparation protocol at Planned Parenthood of Western Pennsylvania between September 2007 and September 2009. Lamicel® osmotic dilators were used for nulliparous women between 12 1/7 and 13 6/7 weeks of gestation and all women 14 to 18 weeks of gestation until September 2008 after which it was no longer available. New guidelines based on available literature included misoprostol 400 mcg vaginally for nulliparous women between 12 1/7 and 13 6/7 weeks of gestation and all women between 14 and 15 6/7 weeks of gestation, and Dilapan-S between 16 and 18 weeks of gestation. Cervical preparation was intended to allow rigid dilation, if necessary, to complete a same-day procedure. We evaluated the ability to complete the procedure on the same day with both protocols and frequency of adverse events. RESULTS: A total of 239 and 168 women received a cervical preparation agent under the old and new protocols, respectively. Demographic characteristics were similar between study cohorts. All procedures in both groups were completed on the same day. Severe complications occurred in two women under the old protocol (excessive bleeding with transfer to hospital) and none with the new protocol. CONCLUSIONS: Early experience for same-day surgical abortion from 12 to 18 weeks of gestation in an outpatient setting using misoprostol and Dilapan-S for cervical preparation is positive in regard to efficacy and safety.

Low-dose fentanyl and midazolam in outpatient surgical abortion up to 18 weeks of gestation.

BACKGROUND: We investigated the safety of a conscious sedation protocol using intravenous fentanyl and midazolam by direct venous injection in women who underwent outpatient surgical abortion up to 18 weeks of gestation. STUDY DESIGN: This retrospective cohort study evaluated 1433 abortion procedures performed on women who received intravenous conscious sedation between April 1, 2001, and December 31, 2006. Women were allowed oral intake before the procedure. De-identified data were abstracted from charts using a standardized extraction form. Primary outcomes evaluated were need for reversal agents, need to obtain emergency intravenous access, pulmonary aspiration, need for oxygen supplementation and hospitalization for any reason. RESULTS: Of the 1433 procedures, 410 women received sedation with continuous intravenous access, and 1023 women received sedation by direct venous injection. More than 95% of women received fentanyl 100 mcg combined with 1-2 mg of midazolam. We identified four (0.3%) instances of adverse events, none of which occurred as a result of oversedation. No women experienced oral content aspiration. CONCLUSIONS: Intravenous conscious sedation with fentanyl and midazolam is safe for outpatient surgical abortion in women without cardiovascular compromise up to 18 weeks of gestation. The risk of aspiration or oversedation requiring reversal agents is rare and does not warrant universal direct venous access or restriction of oral intake.