Deutsche Übersetzung des Titels: Simulation des physiologischen Kalziumsignals zur phasischen Transmitterfreisetzung an einer zentralen Synapse: Kanal-Vesikel-Anordnung und ihre funktionelle Relevanz

Englische Übersetzung des Titels: Modeling physiological calcium signaling for fast transmitter release at a central synapse : topography of release sites and its functional significance

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Übersetzung des Abstracts (Englisch)

This thesis addresses how calcium channels and neurotransmitter vesicles at release sites are spatially organized to control fast synaptic transmission in the central nervous system (topography of release sites). The problem, investigated here for the giant synapse calyx of Held, has been addressed before by a number of studies. However, the large number of poorly known parameters has often defeated attempts to conclude which topography governs presynaptic calcium signaling and thus the transmission characteristics of central synapses. Combining a computer model of buffered calcium diffusion and release with novel analyses of available experimental data, this work answers the following questions: What is the distance between individual calcium channels at release sites? What are the amplitude, spatial profile, and time course of the [Ca2+] signal controlling phasic release? Are channels located randomly or following functional organizing principles, such as clustering? How many channels control the fusion of individual vesicles? And finally, where are these channels located with respect to the vesicles? While providing new insights into prerequisites and feasibility of buffered calcium-diffusion modeling in nerve cells, a particular aim of this study is to clarify the significance of crucial aspects of the topography for the specific physiological function of the synapse.