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The Journal of Neuroscience, January 12, 2005, 25(2):343-351; doi:10.1523/JNEUROSCI.3252-04.2005

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Cellular/Molecular
Activity-Dependent Presynaptic Regulation of Quantal Size at the Mammalian Neuromuscular Junction In Vivo

Xueyong Wang,1 Yingjie Li,1 Kathrin L. Engisch,2 Stan T. Nakanishi,2 Sara E. Dodson,1 Gary W. Miller,1 Timothy C. Cope,2 Martin J. Pinter,2 and Mark M. Rich1,2

1Center for Neurodegenerative Disease and 2Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322

Changes in synaptic activity alter quantal size, but the relative roles of presynaptic and postsynaptic cells in these changes are only beginning to be understood. We examined the mechanism underlying increased quantal size after block of synaptic activity at the mammalian neuromuscular junction in vivo. We found that changes in neither acetylcholinesterase activity nor acetylcholine receptor density could account for the increase. By elimination, it appears likely that the site of increased quantal size after chronic block of activity is presynaptic and involves increased release of acetylcholine. We used mice with muscle hyperexcitability caused by mutation of the ClC-1 muscle chloride channel to examine the role of postsynaptic activity in controlling quantal size. Surprisingly, quantal size was increased in ClC mice before block of synaptic activity. We examined the mechanism underlying increased quantal size in ClC mice and found that it also appeared to be located presynaptically. When presynaptic activity was completely blocked in both control and ClC mice, quantal size was large in both groups despite the higher level of postsynaptic activity in ClC mice. This suggests that postsynaptic activity does not regulate quantal size at the neuromuscular junction. We propose that presynaptic activity modulates quantal size at the neuromuscular junction by modulating the amount of acetylcholine released from vesicles.

Key words: transmitter release; synaptic plasticity; neuromuscular junction; synaptic activity; quantal size; homeostatic


Received Sep 22, 2003; revised October 29, 2004; accepted November 13, 2004.




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