The increasing prevalence of anxio-depressive disorders worldwide suggests that current therapeutic strategies are insufficient in tackling this global health concern. An important element hindering our capacity to treat these mental health issues is our limited knowledge of the cellular mechanisms underlying behavioural dysfunction in psychiatric illness. While most of the mental health research has focused on neuronal cells and how changes of neuronal activity in brain circuits including the amygdala a key brain region that processes threat, the problem of generalized anxiety disorders persists. Our project sets out to further expand our knowledge by investigating the role of astrocytes, a type of non neuronal brain cell, in modulating anxiety. To do this, we will use an innovative approach leveraging recent advances in cellular imaging that will allow us to visualise astrocyte activity in the amygdala during behaviour in freely moving mice.
We will first test how astrocytes integrate anxiety states, investigating astrocyte activity dynamics during behavioural tasks set up to induce anxiety in rodents. Next, we will determine whether modulation of astrocyte activity can tune anxiety states, i.e. increasing or decreasing anxiety. Finally, we will use a stress paradigm that we have shown to induce life-long stress susceptibility, enhancing anxiety and cognitive dysfunction, and determine whether genetic targeting of astrocyte activity and/or stress sensitivity can reverse stress-induced anxiety.
This project offers both fundamental and translational insights as we will gain key insight into how astrocytes influence neural circuits associated with threat detection, and we will attempt to isolate therapeutic targets with clinical translation potential.
