The goal of the proposed project is to determine mechanisms regulating synaptic effectiveness and synaptic plasticity at neuromuscular junctions, using a combined physiological and morphological approach. Synaptic effectiveness will be assessed by estimating the safety margin for neuromuscular transmission and by using intracellular recording and voltage clamping to quantify neurotransmitter release and muscle fiber electrical properties. Light microscopy will be used to search for morphological correlates of synaptic effectiveness at single identified endplates whose release properties have been analyzed. Freeze fracture electron microscopy will be used to correlate average synaptic effectiveness with presynaptic intramembranous ultrastructure. The following naturally occurring and experimentally induced forms of plasticity will be examined: 1) differences in transmitter release between nerve terminals of the same size in different muscles; 2) the dependence of spontaneous and evoked release upon muscle stretch; 3) the increase in release seen in one muscle when its contralateral homologue is denervated; and 4) changes in release that depend on the size of a motoneuron's peripheral field. This project should advance our understanding of how peripheral synapses are regulated and what role these regulatory processes play in normal neuromuscular function and disease-related changes. The major significance of this study, however, may lie in its contribution to understanding comparable synaptic plasticity in the central nervous system. Such plasticity seems to play an important role in the development and maintenance of the brain and its repair following injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Modified Research Career Development Award (K04)
Project #
5K04NS000951-04
Application #
3074804
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1985-05-01
Project End
1990-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
Herrera, A A; Banner, L R; Werle, M J et al. (1991) Postmetamorphic development of neuromuscular junctions and muscle fibers in the frog cutaneous pectoris. J Neurobiol 22:15-28
Werle, M J; Herrera, A A (1991) Elevated levels of polyneuronal innervation persist for as long as two years in reinnervated frog neuromuscular junctions. J Neurobiol 22:97-103
Herrera, A A; Werle, M J (1990) Mechanisms of elimination, remodeling, and competition at frog neuromuscular junctions. J Neurobiol 21:73-98
Herrera, A A; Banner, L R (1990) The use and effects of vital fluorescent dyes: observation of motor nerve terminals and satellite cells in living frog muscles. J Neurocytol 19:67-83
Herrera, A A; Banner, L R; Nagaya, N (1990) Repeated, in vivo observation of frog neuromuscular junctions: remodelling involves concurrent growth and retraction. J Neurocytol 19:85-99
Werle, M J; Herrera, A A (1988) Synaptic competition and the elimination of polyneuronal innervation following reinnervation of adult frog sartorius muscles. J Neurobiol 19:465-81
Werle, M J; Herrera, A A (1987) Synaptic competition and the persistence of polyneuronal innervation at frog neuromuscular junctions. J Neurobiol 18:375-89
Banner, L R; Herrera, A A (1986) Differences in synaptic efficacy at neuromuscular junctions in frog twitch muscles. J Physiol 379:205-15
Propst, J W; Herrera, A A; Ko, C P (1986) A comparison of active zone structure in frog neuromuscular junctions from two fast muscles with different synaptic efficacy. J Neurocytol 15:525-34