Project 460661

While stress is essential for survival and adaptation, intense or unrelenting stress particularly when experienced during development can have long-lasting negative effects. Indeed, stress experienced as a child has been shown to increase the susceptibility to anxiety and depression years later, in adolescence and young adulthood. This is believed to be due to rewiring of neural circuits, heightening sensitivity to stress and susceptibility to anxio-depressive disorders. While much has been studied regarding the effects of early-life stress on neurons, the contribution of non-neuronal cells which comprise over 50% of all brain cells remains poorly defined. Here we propose a project which sets out to recreate a clinically translatable stress paradigm mimicking maternal neglect during a critical neurodevelopmental window. Preliminary data from our lab suggests that early-life stress results in persistent modifications in memory as adults, specifically emotional memory. Our data suggests that manipulation of astrocyte function can influence the strength of stressful memories, highlighting the validity of studying these cells to identify new therapeutic targets to treat stress disorders. In this project we will use genetic manipulations combined with behavioural assays and electrophysiological recordings to further investigate this phenomenon and understand 1) the role of astrocytes in encoding aversive memories 2) how stress affects astrocytes and whether this contributes to cognitive dysfunction, and 3) whether targeting stress signalling in astrocytes alleviates the impact of stress. The goal of our research project is to further our understanding of the biological mechanisms associated with anxiety and depression. A better understanding of how stress affects the brain, and distinct brain cell types, will allow us to identify new therapeutic targets to alleviate the effects of stress and combat the rising rates of mental health disorders.