Mechanisms of presynaptic structural plasticity at hippocampal mossy fiber boutons

• Applicant: Dr. Marta Orlando
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 503954250

This project addresses the cellular and molecular mechanisms of release site re-organization that sustain presynaptic plasticity at hippocampal mossy fiber synapses between dentate gyrus granule cells and CA3 pyramidal neurons. We want to understand if the spatial organization of vesicles and of calcium channel subunits sustains the long-term increase in neurotransmission at potentiated mossy fiber synapses. In particular, we hypothesize that the release of large vesicle content/cargo is inserts new AZ components into the plasma membrane bringing about synaptic strengthening. To this aim, we will use a multidisciplinary approach combining: high-pressure freezing and electron microscopy, live and super-resolution fluorescence microscopy, electrophysiology recordings and optogenetic stimulation. Aim I: Identify the molecular mechanisms responsible for the increase in active zone density Aim II: Investigating synaptic vesicle dynamic organization and its role in plasticity Aim III: Determine the role of calcium channels in presynaptic potentiation Aim IV: Develop strategies for the ultrastructural analysis of optogenetically potentiated synapses

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Dietmar Schmitz