NeuroNetwork 5

The dynamical balance of the brain at rest called resting state (RS) sets crucial parameters for network excitability and intrinsic signal processing. It adapts dynamically to requirements of the optimal brain connectivity and changes of RS leads to an altered input – output assignment. In this definition RS, which has been mainly investigated in human, appears to be related to phenomena broadly referred to as homeostatic and metaplasticity in basic research. Interestingly, the maladaptive RS plasticity is linked with human neuropathologies and effective approaches in their therapy appear to increase neuronal plasticity potentially restoring physiological RS. The failure of RS plasticity was also implemented in the ethiopathology of the major depressive disorder (MDD), which is characterized by aberrant plasticity of glutamatergic transmission and dysregulation of cellular gene expression. Recent clinical trials revealed rapid and long-lasting antidepressant effect of subanaestetic doses of ketamine, a nonselective NMDA receptor antagonist, in treatment-resistant MDD. In this NeuroNetwork we will follow up this finding and study mechanisms of RS plasticity by analyzing the previously shown synaptic strengthening and network remodeling upon administration of ketamine. We will identify the cellular signaling pathways and genes regulated upon ketamine-induced RS plasticity, map the differential brain expression patterns of these genes upon ketamine treatment in animal models and correlate them with patterns of functional connectivity obtained in the human study.