Stress-dependent mental disorders: a molecular and structural basis

We are seeking to study the cellular and molecular mechanisms by which corticotropin releasing factor (CRF) regulates the activity of neural circuits in the cerebellum and hippocampus. To understand this specificity in the context of anxiety and stress coping, one needs an integrated view of the CRF-mediated control of relevant brain regions, and their inter-regional connectivity. Within distinct brain regions, CRF signaling can differentially modulate the activity of multiple cell types (neuronal subtypes, astrocytes and microglia), and in turn can execute context-related alterations in synaptic transmission, resulting in fine-tuned patterns of neuronal activity and depend on refinements of network connectivity. This study will likely identify potential avenues to pharmacological intervention into CRF signaling in neuronal stress responses and will increase our understanding of mechanisms whereby stress modulates dendritic spine morphology, connectivity, and function.