Regulated neurotransmitter release is the basis for neuronal communication. Neurotransmitter is stored in synaptic vesicles and released via fusion with the plasma membrane. Consequently, the dynamics that govern synaptic vesicle morphology and function are deterministic for synaptic function. Synaptic vesicle dynamics can be divided into three segments: fusion, retrieval, and restoration. This application proposes to characterize these segments by capturing synaptic vesicles at accurate times after synaptic vesicle fusion and visualizing their dynamic states in the electron microscope. This approach will be complemented with diverse labeling techniques and genetically encoded markers for electron microscopy.
Communication between nerve cells is mediated via activity-dependent release of neurotransmitter from synaptic vesicles. The morphology, size, molecular composition, and their functional dynamics of synaptic vesicles are thus crucial for brain function. With a set of innovative electron microscopic tools this application aims to determine mechanisms that underlie synaptic vesicle release, retrieval and restoration.
| Cruz-Lopez, Didiana; Ramos, Dianne; Castilloveitia, Gloria et al. (2018) Quintuple labeling in the electron microscope with genetically encoded enhanced horseradish peroxidase. PLoS One 13:e0200693 |
| Afuwape, Olusoji A T; Wasser, Catherine R; Schikorski, Thomas et al. (2017) Synaptic vesicle pool-specific modification of neurotransmitter release by intravesicular free radical generation. J Physiol 595:1223-1238 |
