The function of the nervous system relies on synaptic transmission. Synaptic transmission is mediated by calcium-triggered vesicle fusion, followed by vesicle endocytosis that recycles vesicles. Although significant progress has been made in understanding these processes, much remains unknown. My goal is to advance our understanding of these synaptic signaling processes. The progress of the last year is described below. Studies over the last decade using FM dyes to label vesicles at many terminals, including the calyx-type nerve terminal, led to a well-accepted principle that only a small fraction of vesicles (5-20%) participate in recycling under physiological conditions. This principle imposes a large challenge in maintaining synaptic transmission during repetitive firing, because the small recycling pool may limit the number of available vesicles for release and nerve terminals would have to distinguish the recycling pool from the reserve pool and keep reserve pool vesicles from being used. By recording the presynaptic capacitance changes and the postsynaptic EPSC at rat calyx of Held synapses in the absence or presence of transmitter glutamate in nerve terminals, we developed a new method to count functional recycling vesicles. We found that essentially all vesicles in calyces participated in recycling, challenging the small-recycling-pool principle established by FM dye labeling. Nerve terminals may utilize all available vesicles to maximize their ability in maintaining synaptic transmission during repetitive firing.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Sun, Chong-Kui; Zhou, Di; Zhang, Zhen et al. (2014) Senescence impairs direct conversion of human somatic cells to neurons. Nat Commun 5:4112
Wu, Ling-Gang; Hamid, Edaeni; Shin, Wonchul et al. (2014) Exocytosis and endocytosis: modes, functions, and coupling mechanisms. Annu Rev Physiol 76:301-31
Xiong, Wei; Chen, Shao-Rui; He, Liming et al. (2014) Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease. Nat Neurosci 17:232-9
Cai, Zhenyu; Jitkaew, Siriporn; Zhao, Jie et al. (2014) Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat Cell Biol 16:55-65
Chiang, Hsueh-Cheng; Shin, Wonchul; Zhao, Wei-Dong et al. (2014) Post-fusion structural changes and their roles in exocytosis and endocytosis of dense-core vesicles. Nat Commun 5:3356
Xue, Lei; Sheng, Jiansong; Wu, Xin-Sheng et al. (2013) Most vesicles in a central nerve terminal participate in recycling. J Neurosci 33:8820-6
McNeil, Benjamin D; Wu, Ling-Gang (2009) Location matters: synaptotagmin helps place vesicles near calcium channels. Neuron 63:419-21
Paradiso, Kenneth; Wu, Ling-Gang (2009) Small voltage changes at nerve terminals travel up axons to affect action potential initiation. Nat Neurosci 12:541-3
He, Liming; Xue, Lei; Xu, Jianhua et al. (2009) Compound vesicle fusion increases quantal size and potentiates synaptic transmission. Nature 459:93-7