Communication between a motor neuron and a skeletal muscle fiber takes place at a synapse, the neuromuscular junction. Here both the neuron and muscle fiber are specialized in molecular and structural composition to form the "machinery" required for successful synaptic transmission. Our laboratory is interested in determining the factors involved in the formation and maintenance of the neuromuscular junction.

One of our goals is to determine the contribution of glial Schwann cells and extracellular matrix molecules to nerve terminal stability at the frog neuromuscular junction. The frog neuromuscular junction is a powerful system in which to study synapse stability since nerve terminals studied in the absence of target muscle can reveal nonmuscle stabilization interactions normally masked in the presence of muscle.

Further, the stability of target-deprived nerve terminals can be manipulated to test for stabilization factors using either mature nerve terminals that are stabilized at synaptic sites or regenerated terminals that are unstable in the absence of muscle.

 

 

Elizabeth A. Connor

 Neuromuscular Junction: Development , Function, and Stabilization

Using in vivo repeated imaging of living frog nerve terminals, fluorescent probes, activity dependent dyes, and confocal microscopy, we are testing the contribution of the Schwann cells and matrix molecules in stability of nerve terminals. These experiments will provide needed insight into the nerve-target interactions governing the differentiation, growth, and maintenance of synapses.

A second project is aimed at understanding the role of the actin cytoskeleton in the localization, release and recycling of synaptic vesicles in the frog motor nerve terminal. Using a unique preparation of target-deprived synaptic sites, we discovered that the majority of F-actin in resting motor nerve terminals is external to synaptic vesicle clusters. While the precise localization of synaptic vesicles at active zones is required for synaptic function, presently the mechanisms responsible for their localization and mobilization during release and recycling are not well understood. Combining optical and electrophysiological measures of synaptic function along with direct visualization of the actin cytoskeleton, we are determining if dynamic F-actin participates in the localization, release, or recycling of synaptic vesicles.

 

 

 

 

 

 

Representative Publications:

Connor, E.A., Quin, K., Yankelev, H., and DeStefano, D. (1994). Synaptic activity and connective tissue remodeling in denervated frog muscle. J. Cell Biol. 127, 1435-1445.

Connor, E.A. and Smith, M.A. (1994). Retrograde signaling in the formation and maintenance of the neuromuscular junction. J. Neurobiol. 25: 722-739.

 
Dunaevsky, A. and Connor, E.A. (1995). Long-term maintenance of presynaptic function in the absence of target muscle fibers. J. Neurosci. 15(9): 6137-6144. MEDLINE
 
Connor E. A., Dunaevsky, A., Griffiths, D.J.G., Hardwick, J.C., and Parsons, R. L. (1997). Transmitter release differs at snake twitch and tonic endplates during potassium-induced nerve terminal depolarization. J. Neurophysiol. 77:749-760.

Connor, E. A. (1997). Developmental regulation of interstitial cell density in skeletal muscle. J. Neurocytol. 26:23-32.
 
Dunaevsky, A. and Connor, E.A. (1998). Stability of frog motor nerve terminals in the absence of target muscle fibers. Dev. Biol. 194, 61-71. MEDLINE
 
Dunaevsky, A. and Connor, E.A. (2000). F-Actin is Concentrated in Nonrelease Domains at Frog Neuromuscular Junctions. J. Neurosci. 20(16), 6007-6012.
 
 
 

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