Synaptic Transmission Section - Division of Intramural Research

Ling-Gang Wu, M.D., Ph.D., Senior Investigator

Dr. Wu received his M.D. in 1985 from Second Military Medical College, Shanghai, and his Ph.D. in neuroscience in 1994 from Baylor College of Medicine in Houston, where he worked with Peter Saggau studying how calcium channels control transmitter release. From 1994 to 1996, he was a postdoc in professor William Betz's lab at Univ. Colorado Medical School, where he studied how vesicle endocytosis is regulated. From 1996 to 1999, he was a postdoc in Bert Sakmann's lab at the Max Planck Institute in Heidelberg, Germany, where he studied release mechanisms and short-term synaptic plasticity. From 1999 to 2003 he was an assistant professor at Washington University in St. Louis. Dr. Wu joined NINDS as an investigator in 2003 and was promoted to senior investigator in 2007. His laboratory investigates the fundamental process of synaptic transmission, including how calcium channels control exocytosis, how fusion pores open, close or dilate, how endocytosis is initiated and mediated, and how synaptic plasticity is influenced by calcium channels, fusion pore opening and endocytosis.

Laboratory Staff

Maryna Baydyuk, Ph.D., Postdoctoral Fellow
Hsueh-Cheng Chiang, Ph.D., Research Fellow
Edaeni Hamid, Ph.D., Postdoctoral Fellow
Liming He, Ph.D., Research Fellow
Fujun Luo, Ph.D., Research Fellow
Jiansong Sheng, Ph.D., Research Fellow
Wonchul Shin, Ph.D., Research Fellow
Peter Wen, Ph.D., Postdoctoral Fellow
Xin-Sheng Wu, Ph.D., Research Fellow
Lei Xue, Ph.D., Research Fellow
Zhen Zhang, Ph.D., Visiting Fellow
Weidong Zhao, Ph.D., Research Fellow
Ling-Gang Wu Staff Image

Research Interests

The function of our brain relies on synaptic transmission across billions of synapses in the brain. Regulation of synaptic transmission plays essential roles in many physiological and pathological processes, such as control of neuronal network outputs, neuronal development, learning and memory, and neurological diseases. The Synaptic Transmission Section aims at understanding how synaptic transmission, particularly vesicle exo- and endocytosis at nerve terminals, is mediated and regulated.

Synaptic transmission at nerve terminals is mainly composed of 1) calcium influx via voltage-gated calcium channels during depolarization, 2) calcium-triggered vesicle fusion and fusion pore opening, which releases transmitter and thus generates a postsynaptic current, 3) fusion pore dilation or closure, and 4) retrieval of fused vesicle membrane that recycles exocytosed vesicles. We study the molecular mechanisms underlying each of these key steps using an array of advanced techniques, including whole-cell current and capacitance recordings, cell-attached single channel current and capacitance recordings, epi-fluorescence imaging, confocal and TIRF imaging, super-resolution STED imaging, STORM imaging, ion conductance microscopy, and molecular biological techniques such as over expression, knockdown and knockout. We used three preparations, the giant calyx of Held nerve terminal, the cultured hippocampal synapse and the chromaffin cell.

The lab is often seeking talented and motivated postdoctoral candidates with experience in cell biology (e.g., live-cell fluorescence imaging), molecular biology (e.g., mouse genetics), electrophysiology, or imaging (single vesicle or single molecule imaging). The lab is also often seeking graduate students majored in Neurobiology, Cell Biology, Pharmacology, Genetics, and Biomedical Engineering, with an interest in exo- and endocytosis. Contact Dr. Wu for further information.

Selected Recent Publications

Sheng J, He L, Zheng H, Xue L, Luo F, Shin W, Sun T, Kuner T, Yue DT, Wu LG.
Calcium-channel number critically influences synaptic strength and plasticity at the active zone., Nat Neurosci., 2012, vol. 15(7), pp. 998-1006. Full Text/Abstract
Xue L, McNeil BD, Wu XS, Luo F, He L, Wu LG.
A membrane pool retrieved via endocytosis overshoot at nerve terminals: a study of its retrieval mechanism and role., J Neurosci., 2012, vol. 32(10), pp. 3398-404. Full Text/Abstract
Xue L, Zhang Z, McNell B, Luo FJ, Wu XS, Sheng J, Shin W, Wu LG
Voltage-Dependent Calcium Channels at the Plasma Membrane, but Not Vesicular Channels, Couple Exocytosis to Endocytosis, Cell reports, 2012, vol. 1(6), pp. 632¨C638. Full Text/Abstract
Sun T, Wu XS, Xu J, McNeil BD, Pang ZP, Yang W, Bai L, Qadri S, Molkentin JD, Yue DT, Wu LG.
The role of calcium/calmodulin-activated calcineurin in rapid and slow endocytosis at central synapses., Journal of Neuroscience., 2010, vol. 30(35):, pp. 11838-47. Full Text/Abstract
He L, Xue L, Xu J, McNell B, Bai L, Melicoff E, Adachi R and Wu LG.
Compound vesicle fusion increases quantal size and potentiates synaptic transmission, Nature, 2009, vol. 459, pp. 93-98. Full Text/Abstract
Wu XS, McNeil BD, Xu J, Fan J, Xue L, Melicoff E, Adachi R, Bai L, Wu LG
Ca(2+) and calmodulin initiate all forms of endocytosis during depolarization at a nerve terminal, Nat Neurosci., 2009, vol. 12(8), pp. 1003-10. Full Text/Abstract
Xu J, McNeil B, Wu W, Nees D, Bai L, Wu LG.
GTP-independent rapid and slow endocytosis at a central synapse, Nat Neurosci., 2008, vol. 11(1), pp. 45-53. Full Text/Abstract
Kay AR Alfonso A Alford S Cline HT Holgado AM Sakmann B Snitsarev VA Stricker TP Takahashi M Wu LG
Imaging synaptic activity in intact brain and slices with FM1-43 in C. elegans, lamprey, and rat. , Neuron, 1999, vol. 24, pp. 809-17. Full Text/Abstract

Selected Earlier Publications

Contact Information

Synaptic Transmission Section, NINDS
Porter Neuroscience Research Center
Building 35, Room 2B-1012
35 Convent Drive, MSC 3706
Bethesda, MD 20892-3706

Telephone: 301-451-3338 (office), 301-451-3338 (laboratory), 301-480-1466 (fax)
Email: wul@ninds.nih.gov