Participating in social interactions causes great changes in an individual's behavior and physiology. Some of these changes are very persistent and affect the way an individual behaves or responds physically in subsequent social encounters. These effects are most dramatic in cases where an individual acts aggressively or is the target of aggression from a social rival. In many animal species, such interactions lead to persistent changes in status within a social hierarchy, such as being dominant or subordinate. This project examines the brain changes that result from such aggressive social interactions and the subsequent change into a dominant or subordinate individual. The project focuses on a set of neurochemical agents called "neurotrophins" that are produced and released by neurons and that are known to be important in neural development and modification of brain areas important for learning. The project tests the hypothesis that social interactions cause these neurotrophins to be increased in key brain areas responsible for processing sensory signals, memory formation, and the regulation of emotional and physiological state, and that this increase triggers persistent changes in key brain areas and the social, emotional, and physiological processes they control. Furthermore, it tests the hypothesis that individuals that win aggressive interactions and become social dominants and individuals that lose such interactions and become social dominants show similar neurotrophin changes in sensory and general memory areas, but very different changes in the limbic system brain regions responsible for aggression, reproduction, emotional processing, and hormone regulation leading to very different brain organizations in individuals that experience different outcomes of their social interaction. The results of this project will provide new information about the factors leading to individual differences in aggression and other responses to social challenges and to a better understanding of brain's regulation of social behavior. The project will offer unique opportunities for student training and will expect that these student present their findings at national meetings and as co-authors on peer-reviewed publications.
Social experience is a significant factor in shaping an individual’s future behavior. It also has a strong influence on an individual’s hormone levels and on multiple areas and chemical systems of the brain. This is especially true for experience with social aggression. This project investigated the mechanisms by which experience with aggressive social interactions influenced hormone and brain factors that in turn lead to the persistent behavioral changes. The overarching hypothesis guiding the research is that being the winner vs. being the loser of an aggressive interaction results in two interacting types of hormone-brain changes. First, we predicted that engaging in aggression results in different levels of circulating steroid hormones depending on whether an individual wins or loses an aggressive context, particularly the levels of the reproductive steroid hormones testosterone and estrogen, and the stress steroid hormone corticosterone. Second, we predicted that engaging in aggression changes levels of chemical signaling systems in the brain that regulate brain areas involved in aggression, reproduction, and other types of social behavior. Work to establish baseline behavioral patterns of social aggression prior to the experimental investigation of these hypotheses showed that how persistent an individual was in displaying aggressive behavior was more important in predicting the eventual winner of an aggressive contest than how impulsive or quick it was to respond to a challenge. It also characterized two blood proteins ("binding globulins") that regulate the effective amount of testosterone, estrogen, and corticosterone available to influence brain systems. Experimental studies comparing the hormonal consequences of aggressive interactions in winners and losers found that winners manifested a rapid increase in testosterone levels, and that the action of the identified binding globulins maintained higher levels of testosterone available to the brain up to 10 days after the aggression event. Analysis of brain receptors for testosterone found these were also elevated in winners. These results show that winning aggressive social contests increases both the amount of testosterone and the sensitivity of key brain areas to testosterone. Testosterone is an important regulator of aggression and reproductive social behavior across animals. These results therefore provide insight into how experience with social experience can change an individual’s future levels of aggression and male-female behavior. In addition to persistent changes in hormone levels, changes were seen in several other brain chemical systems important for regulating social behavior, stress, memory formation, and normal brain development as a result of social aggression. These changes last for many days after an individual engages in aggression. Such changes may be the mechanism for persistent behavioral changes that occur after winning aggressive contests, including a greater expression of aggression and a more rapid recovery from stress when faced with future challenges. The persistence of these brain changes suggests that a change in the regulation of gene expression may ultimately be responsible. We found evidence that a process called gene methylation may be involved, as blocking or enhancing this process changed levels of aggression during a social challenge and changed the probability of winning an aggressive interaction. These results indicate that social behavior changes regulatory processes at the molecular level, which in turn would reconfigure of brain systems responsible for social behavioral and physiology. In summary, the results of the project make significant contributions to understanding important, behavioral, hormonal, neural, and molecular processes involved in regulating aggression and distinguishing dominant from subordinate individuals. In addition to its scientific contributions, the project contributed to student training by providing hands-on mentored research experiences to high school students, undergraduates, graduate students including those in doctoral programs and a masters biotechnology training program, and young postdoctoral researchers. In many cases the participants moved on to the next level of science training and careers, capped by three postdoctoral participants becoming faculty members at different universities. The project’s participants also used the research experience as the basis for public outreach as varied as middle school visits to talk to K-12 students and teachers about science and research and working with the Center for Behavioral Neuroscience and ZooAtlanta on interactive animal behavior exhibits. These contributions to STEM education and community science outreach combine with the scientific contributions to the fields of animal behavior, social neuroscience, and social genomics to enhance the broader impacts of the project.
