PROJECT: JTC2023 - Resilience: EnviroMood

Mental health disorders are among the most important health problems worldwide. Since the onset and progression of both disorders are highly affected by contextual factors, the main idea of EnviroMood is that plasticity is an underlying mechanism in both resilience and vulnerability, depending on the environmental context. We hypothesize that it is the environmental valence that determines whether the brain networks are driven towards resilience or vulnerability, and the plasticity states determine to which extent these environmental effects become permanent. EnviroMood will use a back-translational approach to elucidate the environment-plasticity-behavior interaction and its underlying mechanisms: starting from a proof-of-concept trial in humans, we will test a differential modulation of mood by behavioral interventions with positive and negative valence in different states of plasticity. We will then back-translate this approach to animal models in rodents and assess vulnerability and resilience in mouse behavior under different environmental conditions and plasticity-related drug treatment. Furthermore, we will assess drug effects on AMPAR expression, spine and network plasticity. Furthermore, we will use behavioral and ex-vivo experiments to focus on the role of the TrkB pathway, amygdala, and microglia. A more profound understanding of the environment-plasticity-behavior interaction will lead to the development of innovative interventions to promote mental health.