Cognitive disorders are, due to their high frequency and lifelong costs, a leading medical and socio-economical problem world-wide. Particularly for the large number of disorders characterized by intellectual disability, no therapy is available. The search for effective treatment is unlikely to be successful until the pathology of these disorders is better understood. Currently mutations in around 300 human genes are known to cause cognitive disorders. These genes provide an exciting molecular window into fundamental neuroscience and translational research. In 2010, a large international project, FP7 GENCODYS, has been started to characterize their function on the large scale. An early outcome of this project is a systematic library of Drosophila strains that express the fly homologs of human cognitive disorder disease genes as fluorescently tagged (and thus easily traceable) proteins, under their endogenous genomic regulatory control. Combining this novel native reporter toolbox with modern microscopy techniques I propose to create and assemble high-resolution 3D maps of gene expression profiles of these genes in the nervous tissue during embryonic development and in the adult brains of fruitflies, the two conditions most relevant to their associated human disease pathologies. Adult gene expression patterns will be generated under both the steady-state and the stimulated brain activity conditions in order to uncover key factors of neuronal plasticity. We expect these unique charts of plastic neuronal activity to significantly contribute to our understanding of higher brain function in health and disease. They will also facilitate the identification of common molecular pathways that can be targeted for effective treatment of cognitive disorders.
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