Cortical network dysfunctions in response to hyperstimulated Neuregulin/ErbB4 signaling

• Applicant: Privatdozent Dr. Markus Hermann Schwab
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 266993131

Schizophrenia is considered as a synaptic disorder, in which impaired synaptic functions result in cortical network "disconnectivity". The formation of cortical networks and their proper function in the mature brain requires molecular signals that carry information between neural cells. Neuregulin (NRG) 1 is an epidermal growth factor (EGF)-like ligand for receptor tyrosine kinases of the ErbB family and serves as a molecular signal involved in the regulation of normal and aberrant synaptic functions. Variants of the human NRG1 and ErbB4 genes have been identified as candidate risk factors for schizophrenia. Analysis of postmortem brain tissue revealed that increased NRG1 expression and ErbB4 activation occurs in schizophrenia patients, but associated pathomechanisms have not been studied in detail.Genetic mouse models are valuable tools to study the consequences of specific molecular alterations on brain processes in vivo, including mechanisms of pathogenesis. To examine cortical network functions in response to hyperstimulated NRG1/ErbB4 signaling, we have produced several transgenic mouse models, including conditional mouse lines that permit stage- and cell type-specifc NRG1 overexpression. Our goal is to dissect molecular and cellular pathomechanisms mediated by hyperstimulated NRG1/ErbB4 signaling that underly cortical network dysfunctions with relevance for schizophrenia. Identification of these pathomechanisms may contribute to a better understanding of the etiopathophysiology of neuropsychiatric disorders and the development of more potent treatment strategies.

• DFG Programme: Research Grants