@article {4593,
	title = {Reduced release probability prevents vesicle depletion and transmission failure at dynamin mutant synapses.},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {109},
	year = {2012},
	month = {2012 Feb 21},
	pages = {E515-23},
	abstract = {<p>Endocytic recycling of synaptic vesicles after exocytosis is critical for nervous system function. At synapses of cultured neurons that lack the two "neuronal" dynamins, dynamin 1 and 3, smaller excitatory postsynaptic currents are observed due to an impairment of the fission reaction of endocytosis that results in an accumulation of arrested clathrin-coated pits and a greatly reduced synaptic vesicle number. Surprisingly, despite a smaller readily releasable vesicle pool and fewer docked vesicles, a strong facilitation, which correlated with lower vesicle release probability, was observed upon action potential stimulation at such synapses. Furthermore, although network activity in mutant cultures was lower, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity was unexpectedly increased, consistent with the previous report of an enhanced state of synapsin 1 phosphorylation at CaMKII-dependent sites in such neurons. These changes were partially reversed by overnight silencing of synaptic activity with tetrodotoxin, a treatment that allows progression of arrested endocytic pits to synaptic vesicles. Facilitation was also counteracted by CaMKII inhibition. These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis and provide new insight into the coupling between endocytosis and exocytosis.</p>
},
	issn = {1091-6490},
	doi = {10.1073/pnas.1121626109},
	author = {Lou, Xuelin and Fan, Fan and Messa, Mirko and Raimondi, Andrea and Wu, Yumei and Looger, Loren L and Ferguson, Shawn M and De Camilli, Pietro}
}
