Several lines of evidence indicate that the number and distribution of axonal contacts on postsynaptic cells are regulated by competitive interactions between axons duuring development.
The aim of is to better understand the developmental strategies that regulate this competition. The studies will utilize several newly developed techniques for the visualization of synaptic terminals in living preparations under the light microscope. The normally occurring competitive reduction in the number of axons that innervate a postsynaptic cell will be followed by viewing the terminals of different axons made visible in a novel way by activity dependent tracer uptake. Brief activation of a motor axon in the presence of any one of several differently colored fluorescent molecules selectively fills the synaptic terminals of that axon with the tracer. By stimulating different axons in the presence of different colored probes, the precise distribution of the synaptic terminals of different axons can be described. This simple and powerful technique will be used to characterize the normally occurring competitive reduction in the number of axons that innervate a muscle fiber in both snakes and mammals. The second goal is to study anatomically and electrophysiologically the same nerve terminals over time as synaptic remodelling is taking place. The finding that a previously unused fluorescent probe selectively stains mammalian motor nerve terminals with virtually no toxicity and extremely low background has for the first time permitted multiple views of the same mammalian junctions at different time points. This fluorescent molecule will be used to monitor the reorganization of synaptic connections at individual mammalian neuromuscular junctions in living mice during muscle reinnervation. Studying synaptic competition at living terminals will provide direct information about the dynamic aspects of synaptic remodelling -- a subject which is very poorly understood and presumably is the basis of some of the most important long-term changes in the nervous system (e.g., learning and memory).
| Sheu, Shu-Hsien; Tapia, Juan Carlos; Tsuriel, Shlomo et al. (2017) Similar synapse elimination motifs at successive relays in the same efferent pathway during development in mice. Elife 6: |
| Turney, Stephen G; Lichtman, Jeff W (2012) Reversing the outcome of synapse elimination at developing neuromuscular junctions in vivo: evidence for synaptic competition and its mechanism. PLoS Biol 10:e1001352 |
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| Jeong, Wan-Ki; Beyer, Johanna; Hadwiger, Markus et al. (2010) Ssecrett and NeuroTrace: interactive visualization and analysis tools for large-scale neuroscience data sets. IEEE Comput Graph Appl 30:58-70 |
| Jeong, Won-Ki; Schneider, Jens; Turney, Stephen G et al. (2010) Interactive histology of large-scale biomedical image stacks. IEEE Trans Vis Comput Graph 16:1386-95 |
| Lu, Ju; Min, Wei; Conchello, José-Angel et al. (2009) Super-resolution laser scanning microscopy through spatiotemporal modulation. Nano Lett 9:3883-9 |
| Gan, Wen-Biao; Grutzendler, Jaime; Wong, Rachel O et al. (2009) Ballistic delivery of dyes for structural and functional studies of the nervous system. Cold Spring Harb Protoc 2009:pdb.prot5202 |
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