Serotonergic modulation of aggressive and prosocial behaviors

Stanford University, Stanford CA

Investigators

Abstract

Low frustration tolerance and excessive aggression are major causes of suffering across multiple psychiatric disorders. Although foundational work has revealed neural populations in the amygdala, hypothalamus, and brainstem that are necessary to trigger aggressive behavior, the upstream circuits that modulate this behavior depending on context are less understood. Furthermore, aggression is just one of multiple social behaviors, and it remains unclear how the brain facilitates flexible transitions between these behaviors. In this project, we aim to remedy these gaps in the literature by exploring the possible mechanistic links between aggression and its counterpart: prosocial, affiliative behavior. We take advantage of preliminary data in mice demonstrating that serotonin release in the nucleus accumbens (NAc) both increases prosocial behavior and reduces aggression. Here we ask how these two behavioral effects might interact at a neural level. In Aim 1 (temporal target), we combine optogenetic manipulations with serotonin sensor recordings to characterize the temporal dynamics of serotonin’s effects on prosocial behavior and aggression. In Aim 2 (cellular target), we use miniaturized microscopes to identify the subpopulation(s) of NAc neurons that respond to serotonin to mediate its behavioral effects. In Aim 3 (contextual target), we “frustrate” mice by training them to expect a reward and blocking them from achieving it. We then combine neural recordings and optogenetic manipulations to discover how serotonin and NAc neurons adapt to this pro-aggressive and anti-social contextual manipulation. Our findings have the potential to resolve longstanding debates over the role of serotonin in social behavior, introduce new methods to resolve the timing and cellular mediators of neuromodulator action, and discover the neural circuits that link reward omission (frustration) with aggression. Ultimately, the research aims to facilitate ‘precision psychiatry’ treatments that harness the circuit and molecular specificity we identify here to help alleviate the suffering of patients with maladaptive aggressive behavior.