Frequency-dependent modes of synaptic vesicle endocytosis and exocytosis at adult XXXX neuromuscular junctions.

@entity19 @entity17173 @entity5222 @entity23452 @entity141 @entity393
During locomotion, adult rodent lumbar motoneurons fire in high-frequency (80-100 Hz) 1-2 s bursts every several seconds, releasing between 10,000 and 20,000 vesicles per burst. The estimated total vesicle pool size indicates that all vesicles would be used within 30 s; thus, a mechanism for rapid endocytosis and @entity5222 is necessary to maintain effective transmission and motor behavior. However, whether such rapid recycling exists at @entity19 neuromuscular junctions (NMJs) or how it is regulated has been unclear. Here, we show that much less FM1-43 dye is lost per stimulus with 100 Hz stimulation than with 10 Hz stimulation even when the same number of vesicles undergo exocytosis. Electrophysiological data using @entity17173 show this lesser amount of @entity393 is caused in part by the rapid reuse of vesicles. We showed previously that a @entity23452 ( @entity23452 )-myosin II pathway was required for effective transmission at 100 Hz. Here, we confirm the activation of @entity23452 , based on increased nerve terminal phospho-MLC immunostaining, with 100 Hz but not with 10 Hz stimulation. We further demonstrate that activation of @entity23452 , by increased extracellular @entity141 , by PKC (protein kinase C) activation, or by a @entity23452 agonist peptide, reduces the amount of dye lost even with 10 Hz stimulation. @entity23452 activation at 10 Hz also resulted in more vesicles being rapidly reused. Thus, @entity23452 activation by 100 Hz stimulation switches the mechanism of vesicle cycling to a rapid-reuse mode and is required to sustain effective transmission in adult @entity19 NMJs.
