Our long term objectives are to understand the cellular mechanisms by which synapses are eliminated at the neuromuscular junction. During normal development of the nervous system, more synapses are initially formed than will persist to adulthood. The withdrawal of some synaptic connections plays an important role in shaping the final """"""""wiring diagram"""""""" of the nervous system, and consequently it is important in shaping the functional capabilities of all higher animals. There is good evidence that the converging synapses are competing with each other in some way, but the cellular mechanisms underlying the competition are unknown. We have observed in preliminary studies that when two axons converge upon a single muscle fiber, stimulation of one nerve can depress the amplitude of the synaptic potential produced in response to stimulation of the other nerve. The depression appears to be maximal about 30 milliseconds after the conditioning stimulus, and lasts about 100 milliseconds. We propose to investigate the physiological basis of this interaction by studying the effects of various drugs and ions on the interaction. In addition, we will study the morphological relations between nerve terminals with the electron microscope, after selectively labelling some of the nerve endings with horseradish peroxidase. We also have begun to develop an in vitro preparation of spinal cord, peripheral nerve, and muscle, all dissected in continuity. We propose to characterize this preparation in more detail. If synapse elimination can be reliably detected, as preliminary observations suggest, we will then be able to study the cellular mechanisms of synapse elimination by altering the composition of the bathing medium and the electrical activity of the nerves to the muscle.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023466-03
Application #
3406975
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-07-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Gaffield, Michael A; Romberg, Christin F; Betz, William J (2011) Live imaging of bulk endocytosis in frog motor nerve terminals using FM dyes. J Neurophysiol 106:599-607
Gaffield, Michael A; Tabares, Lucia; Betz, William J (2009) The spatial pattern of exocytosis and post-exocytic mobility of synaptopHluorin in mouse motor nerve terminals. J Physiol 587:1187-200
Gaffield, Michael A; Tabares, Lucia; Betz, William J (2009) Preferred sites of exocytosis and endocytosis colocalize during high- but not lower-frequency stimulation in mouse motor nerve terminals. J Neurosci 29:15308-16
Rizzoli, Silvio O; Betz, William J (2004) The structural organization of the readily releasable pool of synaptic vesicles. Science 303:2037-9
Brumback, Audrey C; Lieber, Janet L; Angleson, Joseph K et al. (2004) Using FM1-43 to study neuropeptide granule dynamics and exocytosis. Methods 33:287-94
Rizzoli, Silvio O; Richards, David A; Betz, William J (2003) Monitoring synaptic vesicle recycling in frog motor nerve terminals with FM dyes. J Neurocytol 32:539-49
Rizzoli, Silvio O; Betz, William J (2002) Effects of 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one on synaptic vesicle cycling at the frog neuromuscular junction. J Neurosci 22:10680-9
Adlard, K; Tsaknardis, L; Beam, A et al. (1999) Immunoregulation of encephalitogenic MBP-NAc1-11-reactive T cells by CD4+ TCR-specific T cells involves IL-4, IL-10 and IFN-gamma. Autoimmunity 31:237-48
Wu, L G; Betz, W J (1996) Nerve activity but not intracellular calcium determines the time course of endocytosis at the frog neuromuscular junction. Neuron 17:769-79
Henkel, A W; Simpson, L L; Ridge, R M et al. (1996) Synaptic vesicle movements monitored by fluorescence recovery after photobleaching in nerve terminals stained with FM1-43. J Neurosci 16:3960-7

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