Neural mechanisms of stress coping and maladaptive changes in affective disorders
Coping with different stressors is essential for survival and success, which is regulated by complex neural networks integrating cognitive and emotional processes. Under pathological conditions, excessive passive coping becomes detrimental, observed in anxiety and depressive disorders. Animal models can help to identify the neural substrates of individual vulnerability to develop such maladaptive conditions. We use rodent models (transgenic mice, early-life stress, cell type-specific manipulations) to explore the molecular, cellular, neuronal network level changes underlying anxious-depressive phenotypes.
Our recent studies revealed that altered maturation of specific cell types (somatostatin interneurons) significantly changes cortical network function in association with changes in stress coping behavior. We also identified brain regions that determine such changes, e.g. prefrontal and insular cortices, which are known for their integrative role of external and internal stimuli in order to shape adequate behavioral decisions and responses. We are currently investigating gene expression and neural network changes in vulnerable-depressive individuals using RNA sequencing and whole-brain and immunohistochemistry across the whole brain. In this approach, we apply automated microscopy-imaging with deep learning algorithms to explore neural networks on a large scale in an unbiased manner.