The rearrangement of synaptic connections (""""""""synapse elimination"""""""") occurring in neonatal rat soleus and extensor digitorum longus muscles will be examined. The proposed project has four long term objectives. (1) To understand the relationship between synapse elimination and the generation of motor units composed of a single type of muscle fiber. The development of different types of muscle fibers in new-born muscle will be determined using ATPase histochemistry and the fibers innervated by single motor neurons at different postnatal ages ascertained using the technique of glycogen depletion. Since muscle fiber types are already differentiated at a stage when these fibers are still multiply innervated, this study will show how homogeneous motor units are created during postnatal development. (2) To investigate the role of neuromuscular activity in determining which synapses are displaced from muscle fibers. The activity of a portion of the innervation of rat soleus muscle will be increased by stimulation and it will be determined whether the more active motor neurons are favored over the less active ones in maintaining their inputs on muscle fibers. The results of these experiments should give some indication of where (the synapse or the muscle fiber) activity is important in synapse elimination. (3) To examine muscles during the period of synapse elimination to determine whether physiological changes in terminals precede their elimination. Intracellular records will be made of the end-plate potentials obtained by repetitively stimulating single motor neurons. (4) To determine whether the competition for elimination of motor nerve terminals is affected by the number of competing motor neurons. Synapse elimination will be compared in rat strains having differing numbers of soleus motor neurons and a constant number of soleus muscle fibers. The results of this study will further knowledge of the development of synaptic connections in muscle.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020480-02
Application #
3400817
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1984-06-01
Project End
1987-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78713
Lee, Young Il; Thompson, Wesley J; Harlow, Mark L (2017) Schwann cells participate in synapse elimination at the developing neuromuscular junction. Curr Opin Neurobiol 47:176-181
Lee, Young Il; Li, Yue; Mikesh, Michelle et al. (2016) Neuregulin1 displayed on motor axons regulates terminal Schwann cell-mediated synapse elimination at developing neuromuscular junctions. Proc Natl Acad Sci U S A 113:E479-87
Kang, Hyuno; Tian, Le; Mikesh, Michelle et al. (2014) Terminal Schwann cells participate in neuromuscular synapse remodeling during reinnervation following nerve injury. J Neurosci 34:6323-33
Smith, Ian W; Mikesh, Michelle; Lee, Young il et al. (2013) Terminal Schwann cells participate in the competition underlying neuromuscular synapse elimination. J Neurosci 33:17724-36
Li, Yue; Lee, Young il; Thompson, Wesley J (2011) Changes in aging mouse neuromuscular junctions are explained by degeneration and regeneration of muscle fiber segments at the synapse. J Neurosci 31:14910-9
Brill, Monika S; Lichtman, Jeff W; Thompson, Wesley et al. (2011) Spatial constraints dictate glial territories at murine neuromuscular junctions. J Cell Biol 195:293-305
Li, Yue; Thompson, Wesley J (2011) Nerve terminal growth remodels neuromuscular synapses in mice following regeneration of the postsynaptic muscle fiber. J Neurosci 31:13191-203
Lee, Young Il; Mikesh, Michelle; Smith, Ian et al. (2011) Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons. Dev Biol 356:432-44
Kang, Hyuno; Tian, Le; Son, Young-Jin et al. (2007) Regulation of the intermediate filament protein nestin at rodent neuromuscular junctions by innervation and activity. J Neurosci 27:5948-57
Hayworth, Christopher R; Moody, Susan E; Chodosh, Lewis A et al. (2006) Induction of neuregulin signaling in mouse schwann cells in vivo mimics responses to denervation. J Neurosci 26:6873-84

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