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Regulation of synapse formation, plasticity and function by astroglial-derived extracellular matrix - tenascin-C and interacting proteoglycan ligands
Antragsteller
Professor Dr. Andreas Faissner
Fachliche Zuordnung
Molekulare Biologie und Physiologie von Nerven- und Gliazellen
Förderung
Förderung von 2004 bis 2007
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5431949
The sprouting and pruning of synapses constitute important morphological correlates of synaptic plasticity in the adult nervous system. Electrical activity plays an important regulatory role in this context. By comparison, less is known about the cellular and molecular bases of these processes. Perturbation assays and gene elimination by recombinant techniques have provided clear indications that astroglialderived extracellular matrix components, e.g. the ECM glycoprotein tenascin-C, are involved in synapse maturation and plasticity. It has been shown in preliminary studies that tenascin-C and the glial-derived chondroitinsulfate proteoglycan phosphacan modulate neurite sprouting of primary embryonic CNS neurons. Complementary receptors for distinct cellular functions have been characterized. These studies shall be continued in order to characterise the mechanisms by which astrocyte-derived ECM controls synapse formation, maturation and function. Two in vitro models will be studied, namely cultures of embryonic hippocampal and of olfactory glomerular neurons. Synaptogenesis, functional properties and modulation of synaptic activity will be assessed using electrophysiological measurement and advanced imaging techniques. Particular emphasis will be given to receptors, postsynaptic physiological modifications and corresponding downstream signaling pathways in responsive neurons.
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