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).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020364-05
Application #
3400705
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-12-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
5
Fiscal Year
1988
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:
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