Background: Aggression can be learned by observing the aggressive behavior of others, which can be advantageous for survival, but can also have severe consequences for the individual and society at large. Notably, children frequently exposed to aggressive behavior have an increased risk of engaging in violent acts later in life. It is unclear how exposure to aggression leads to the development of aggressive tendencies, but it is hypothesized that individuals may model their behavior based on their familiarity with the aggressor. However, testing this hypothesis is difficult due to ethical and logistical constraints. Prior Research and Preliminary Data: Our lab recently developed a novel social transmission paradigm to investigate learned aggression in mice. We find that mice are more likely to attack a novel conspecific after witnessing a familiar attacking demonstrator. The witnesses also show increased activity in the medial amygdala (MeApv) and ventromedial hypothalamus (VmHvl), similar to our previous studies on aggression priming. The primary objective of this proposal is to study the role of familiarity in socially transmitted aggression in mice so as to better understand the underlying brain mechanisms, which may lead to the development of improved therapeutics. The central hypothesis is that socially transmitted aggression depends on the activation and potentiation of an excitatory MeApv-VmHvl pathway in familiar pairs of mice. To test this hypothesis, we will perform two sets of experiments using our social transmission paradigm: (1) Investigate the function of MeApv neurons in socially transmitted aggression using chemogenetics; (2) Examine the role of synaptic plasticity at MeApv-VmHvl synapses in modulating socially transmitted aggression using electrophysiology and optogenetics. This project is conceptually innovative as it addresses for the first time how familiarity, MeApv activity, and MeApv-VmHvl synaptic plasticity drive socially transmitted aggression. This project will also aid in determining the role of familiarity in social behavior in general. This study is a new direction for the lab that builds on our existing knowledge base and skill set, ideally suited for the R21 mechanism. This project is technically innovative because it will use our novel behavior paradigm with chemogenetics, optogenetics, and electrophysiology, methods we are expert in, to identify the role of the MeApv-VmHvl pathway in socially transmitted aggression. The experiments will also examine sex-specific effects, as aggression priming occurs in both males and females. The research is significant because it utilizes a novel behavioral paradigm in mice to model the long-observed but poorly understood phenomenon of socially transmitted aggression. The long-term goal of this research is to elucidate the neural mechanisms of familiarity and socially transmitted aggression, which if achieved will provide valuable insights into the development and perpetuation of aggressive behavior. Findings from this proposal will have a positive impact as it has the potential to lead to improved therapeutic interventions for controlling aggressive tendencies in individuals exposed to violence, thereby reducing the cycle of abuse and its impact on society.

The proposed research is relevant to public health and the current objective of the NIMH to elucidate the brain mechanisms underlying affective and social processes such as aggression. The project is conceptually and technically innovative because it uses cutting-edge techniques to assess the neural pathways and mechanisms involved in socially transmitted aggression. This project addresses the priority of NIMH to conduct research on aggression and violence against others that will eventually lead to new diagnostic and therapeutic strategies to manage pathological anger and violence.