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Projekt
Role of APP in homeostatic synaptic plasticity in the hippocampus
Antragstellerinnen / Antragsteller
Professor Dr. Thomas Deller; Professorin Dr. Ulrike Müller; Professor Dr. Andreas Vlachos
Fachliche Zuordnung
Molekulare Biologie und Physiologie von Nerven- und Gliazellen
Förderung
Förderung von 2010 bis 2018
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 138733498
Following traumatic injury of the adult brain, APP is upregulated at injury sites and in denervated brain regions. Since APP and its fragment APPsα are involved in the regulation of synaptic plasticity and, furthermore, have potent neuroprotective effects in vitro, it has been speculated that the induction of APP after brain injury could enhance reorganization responses of surviving neurons.Using organotypic slice cultures of mutant mouse hippocampus, the role of APP and, in particular, APPsα in structural and functional brain reorganization will be studied. Time-lapse confocal imaging will be employed to visualize structural changes (dendritic remodelling, axonal sprouting) and whole-cell patch clamp recordings will be used to study functional effects. Furthermore, it will be addressed how the APPsα effects are mediated. Using a combination of genetic and pharmacological approaches, we will study whether APPsα signalling involves APP and changes in intracellular calcium levels. To study the effect of an enhanced endogenous APPsα production on neuronal reorganization, a Thy1-APPsα transgenic mouse will be generated. Finally, we will verify the in vivo relevance of our findings by performing denervation experiments on the mouse mutants in vivo. Because ofthe complementary methodological expertise of the two groups involved in this proposal the role of APP and its fragment APPsα in denervation-induced plasticity will be studied with high efficiency.
DFG-Verfahren
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