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Blocking endocytosis enhances short-term synaptic depression under conditions of normal availability of vesicles

Item Type:Article
Title:Blocking endocytosis enhances short-term synaptic depression under conditions of normal availability of vesicles
Creators Name:Hua, Y. and Woehler, A. and Kahms, M. and Haucke, V. and Neher, E. and Klingauf, J.
Abstract:It is commonly thought that clathrin-mediated endocytosis is the rate-limiting step of synaptic transmission in small CNS boutons with limited capacity for synaptic vesicles, causing short-term depression during high rates of synaptic transmission. Here, we show by analyzing synaptopHluorin fluorescence that 200 action potentials evoke the same cumulative amount of vesicle fusion, irrespective of the frequency of stimulation (5-40 Hz), implying the absence of vesicle reuse, since the method used (alkaline-trapping) measures only first-round exocytosis. After blocking all slow or specifically clathrin-mediated endocytosis, however, the same stimulation patterns cause a rapid stimulation-frequency-dependent release depression. This form of depression does not reflect insufficient vesicle supply, but appears to be the result of slow clearance of vesicular components from the release site. Our findings uncover an important yet overlooked role of endocytic proteins for release site clearance in addition to their well-characterized role in endocytosis itself.
Keywords:Electric Stimulation, Endocytosis, Hippocampus, Hydrazones, Neurons, Primary Cell Culture, Synaptic Transmission, Synaptic Vesicles, Vesicular Transport Adaptor Proteins, Animals, Rats
Source:Neuron
ISSN:0896-6273
Publisher:Cell Press
Volume:80
Number:2
Page Range:343-349
Date:16 October 2013
Official Publication:https://doi.org/10.1016/j.neuron.2013.08.010
PubMed:View item in PubMed

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