Role of excitation-inhibition in Rett syndrome

Project Leader: Christian Rosenmund e-mail

 

Loss of function mutations in the X-linked gene encoding the transcriptional repressor, methyl-CpG binding protein 2 (MECP2) results in the development of Rett syndrome (RTT). We propose that MeCP2 dysfunction results in abnormal excitatory-inhibitory neuronal activity, and that the expression level of MeCP2 is critical for balance development and function of networks. Objective of this research proposal is to elucidate the physiological and pathophysiological role of MeCP2 variable and graded expression on central synapse function and synapse formation. We aim to study the interaction of excitation and inhibition in a novel culture system and finally study the interaction of MeCP2 with the glucocorticoide system in synaptic function,that glucocorticoids have been recently shown to strongly interfere with morbitidy in RTT mouse models. These studies aim to provide important insights in the pathophysiology of RTT and other autism related developmental disorders.