Several lines of evidence suggest that the number and distribution of axonal contacts on postsynaptic cells are regulated by competitive interactions between axons during development.
The aim of this work is to better understand the developmental strategies that regulate this competition. The studies will utilize new techniques that allow for visualization of individual terminals in living preparations under the light microscope. The normally occurring competitive reduction in the number of terminals that innervate a muscle fiber (synapse elimination) will be followed by viewing terminals of one axon that have been made visible by activity dependent tracer uptake. Preliminary experiments indicate that it is possible (a) to activate an individual identified motor axon and its motor unit in the transversus abdominis muscle of the garter snake by extracellular stimulation, (b) To identify neurally activated nerve terminals in the light microscope using uptake of fluorescein-dextran or a peroxidase enzyme, and (c) to see peroxidase filled processes in vivo by the enzyme mediated conversion of L-DOPA into melanin. Our objective is to use these techniques in order to observe the competitive process which results in the 'capture' of an endplate by one axon. Among the questions this project aims to answer are: (1) Does axonal competition proceed by means of physical contact among terminals or does competition occur at a distance? (2) What is the relationship between the elimination and proliferation of synapses which occur concurrently during development? (3) Does synapse elimination play a role in creating qualitative specificity (e.g., matching of types of motor axon and fiber). Answers to these questions are fundamental to understanding the basis of appropriate connectivity between nerve cells and their targets. The transversus abdominis muscle of the garter snake is an advantageous preparation since it is only one fiber in thickness, enabling excellent visability of all the neuromuscular contacts. Moreover, it contains several types of innervating axons and muscle fibers which are arranged in a stereotyped repeating pattern.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020364-02
Application #
3400703
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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
Roberts, Mike; Jeong, Won-Ki; Vazquez-Reina, Amelio et al. (2011) Neural process reconstruction from sparse user scribbles. Med Image Comput Comput Assist Interv 14:621-8
Fox, Michael A; Tapia, Juan Carlos; Kasthuri, Narayanan et al. (2011) Delayed synapse elimination in mouse levator palpebrae superioris muscle. J Comp Neurol 519:2907-21
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
Kasthuri, Narayanan; Lichtman, Jeff W (2010) Neurocartography. Neuropsychopharmacology 35:342-3
Srinivasan, Ranga; Li, Qing; Zhou, Xiaobo et al. (2010) Reconstruction of the neuromuscular junction connectome. Bioinformatics 26:i64-70
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

Showing the most recent 10 out of 26 publications