Depressive disorders affect more than 280 million people worldwide and its pathophysiology is still poorly understood. Depressive behavior is characterized in humans and animal models by persistent mood and cognitive impairments. These effects were consistently correlated with alterations in neuronal function and structure in cortico-limbic regions. While in physiological conditions astrocytes actively support neuronal function, our preliminary experiments show that modulating astrocytes causes resilience to the depressive pathology.

We hypothesize that the depressive pathology might result from over-activation of astrocytes in cortico-limbic networks. Thus, we propose to combine multidisciplinary approaches (behavioral, electrophysiological, transcriptomic) to IDENTIFY new region- and cell-specific molecular targets involved in depressive resilience. Moreover, we will produce novel tools to genetically manipulate these targets, and we will TEST their therapeutic potential.