Guangfu Wang studied at the School of Electronics Engineering and Computer Science (EECS) of Peking University (PKU), where he received a B.S degree in electronics and a Ph.D. degree in radio physics in 2003 and 2008, respectively. In the nine years of study and research in PKU, Wang accumulated solid knowledge in electronics, physics and computer science by accomplishing various projects, including precision current controller & temperature controller for laser diodes, holographic optical tweezers, and neutral atomic optical frequency standards. After graduating from PKU, he realized that his true passion was interdisciplinary study of physics and biology, and then joined Julius Zhu lab in University of Virginia (UVa) for neuroscience study. In the following years, Dr. Wang overcame various mechanical, electronic, optical and software barriers, and independently built up an experimental setup featuring octuple whole-cell recording, two-photon imaging and one-/two-photon optogenetic stimulation. So far, using this setup, Dr. Wang and colleagues have accomplished several projects related to neuronal circuitry and synaptic function, and published the results in high-ranked journals. They discovered two layer 1 (L1) neuron-led disinhibitory and inhibitory neuronal circuits that control the initiation of the dendritic potentials. They found that these two circuits act synergistically with the dendritic coincidence mechanism to achieve salience selection. This body of work deciphers the organization of cortical L1 neuron-led transsynaptic circuits at cellular and subcellular levels. It reveals the essential role of the interneuronal circuits in governing salience selection during the attention-demanding tasks (e.g., attentional, expectational, perceptual and working memory tasks). Dr. Wang’s other focus is synaptic plasticity and its regulation. He investigated how the disease-linked mutant proteins may affect AMPA and NMDA receptor-mediated transmissions, and lead to defects in synaptic plasticity, learning and memory. He explored the manipulations that may reverse the impaired cognition. Hitherto, Dr. Wang has investigated CaV3.2 channel relating to childhood absence epilepsy, BRAG1 relating to X-linked mental disorder, DISC1 relating to schizophrenia, and FXR2P relating to fragile X syndrome. His work built the foundation for developing effective therapies for these cognitive disorders. Dr. Wang has joined the School of Life Sciences and Technology of he Harbin Institute of Technology in December, 2017.
Research Interests
My current research focuses on medial entorhinal cortex (MEC). MEC is the interface between hippocampus and neocortex, and is believed to play an important role in spatial navigation, learning, and memory. Actually MEC has been reported to contain diverse spatial cell types, including grid cells, head direction cells, border cells, and speed cells. Grid cells, which have multiple firing fields forming a hexagonal grid, are the most important spatial cells. Since first discovered in rats, grid cells have also been found in mice, bats, monkeys and humans. Together with place cells in hippocampus, grid cells form a comprehensive positioning system, an inner GPS, in the brain, while other spatial cells, especially head direction and speed cells, are believed to offer information to grid cells to perform path integration. In the past decade, in vivo recordings of grid and other spatial cells deepened our understanding of them, but how the grid firing fields form is still an enigma. Answering this question requires not only more detailed behavior studies but also a comprehensive knowledge of cellular properties and neuronal circuits in MEC. Therefore, my interest is to reveal cellular and circuitry fundamentals of spatial cells in MEC. Specifically, I will investigate the mechanism of grid and other spatial cells using multiple independent approaches combining electrophysiology, optogenetics, two-photon imaging, molecular biology, and pharmacology, and focus on the following three aims:
Aim 1: To investigate cell types and local circuitry in MEC.
Aim 2: To investigate the dorsal-ventral organization of cells and circuits in MEC.
Aim 3: To investigate the afferent inputs from visual cortex to MEC.
Moreover, I will also develop in vivo recording system of spatial cells, employing tetrode, juxtacellular, and/or fluorescence recordings. After establishing the recording system, I will long to study the effect of external sensory clues and environmental spatial frequency on spatial cells. In addition, I am also interested in developing and applying new optical technology, especially techniques combining nanoscience. By attaching gold nanoparticles on the cellular surface, neurons can be activated optically in subcellular resolution. Combined with intracellular nanoprobes, surface-enhanced Raman spectroscopy has been used to distinguish different cell types of neurons. I am eager to see whether these new approaches can assist my neuronal circuitry study in finding neural connections and determining cell types of interneurons.
Techniques and Tools in the Lab
Simultaneous multiple whole-cell recording
Morphological reconstruction of neurons
Two-photon Ca2+/Na+ imaging
One-/two-photon optogenetic stimulation
Viral tools (Sindbis virus, lentivirus, AAV)
Fluorescence sensors (acetylcholine, serotonin, dopamine, glucose, etc.)
Selected Publications(# Co-first author; *Corresponding author)
Lim CS, Wen C, Sheng Y,Wang G, Zhou Z, Wang S, Zhang H, Ye A, Zhu JJ (2017) Piconewton-Scale Analysis of Ras-BRaf Signal Transduction with Single-Molecule Force Spectroscopy.Small:DOI: 10.1002/smll.201701972. [IF: 8.643]
Reported as news byPhys.org (https://phys.org/news/2017-09-technique-doctors-disease-severity.html) andCBS (http://www.newsplex.com/content/news/UVA-researchers-develop-new-molecule-measuring-technique-444053003.html).
Wang G, Bochorishvili G, Chen Y, Salvati KA, Zhang P, Dubel SJ, Perez-Reyes E, Snutch TP, Stornetta RL, Deisseroth K, Erisir A, Todorovic SM, Luo JH, Kapur J, Beenhakker MP, Zhu JJ (2015) CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence-like epilepsy.Genes Dev29:1535-1551. [IF: 9.413]
See commentary inEpilepsy Currents16:36–38.
Wang G#, Wyskiel DR#, Yang W, Wang Y, Milbern LC, Lalanne T, Jiang X, Shen Y, Sun Q-Q and Zhu JJ (2015) An optogenetics- and imaging-assisted simultaneous multiple patch-clamp recordings system for decoding complex neural circuits.Nat Protoc10: 397-412. [IF: 10.032]
Highlighted as the cover article byNature Protocols.
Lee AJ#,Wang G#, Jiang X#, Johnson SM, Hoang ET, Lanté F, Stornetta RL, Beenhakker MP, Shen Y, Zhu JJ (2015) Canonical Organization of Layer 1 Neuron-Led Cortical Inhibitory and Disinhibitory Interneuronal Circuits.Cereb Cortex25:2114-2126. [IF: 6.559]
Wang G and Zhu JJ (2014) DISC1 dynamically regulates synaptic N-methyl-D-aspartate responses in excitatory neurons.Biol Psychiatry75: 348-350. [IF: 11.412]
Invited commentary.
Jiang X#,Wang G#, Lee AJ, Stornetta RL and Zhu JJ (2013) The Organization of Two New Cortical Interneuronal Circuits.Nat Neurosci16: 210-218. [IF: 17.839]
See news and views inNature Neurosci16:114-5; highlights inCurr Opin Neurobiol 26:7-14,Curr Opin Neurobiol 26:15-21,Curr Opin Neurobiol26:117-124, andCurr Opin Neurobiol32:107-14.
Myers KR#,Wang G#, Sheng Y, Conger KK, Casanova JE and Zhu JJ (2012) Arf6-GEF BRAG1 Regulates JNK-Mediated Synaptic Removal of GluA1-Containing AMPA Receptors: A New Mechanism for Nonsyndromic X-Linked Mental Disorder.J Neurosci32: 11716-11726. [IF: 5.988]
Ye A andWang G* (2008) Dipole polarizabilities ofns21S0 andnsnp3P0 states and relevant magic wavelengths of group-IIB atoms.Phys Rev A78: 1-4 (Article #: 014502). [IF: 2.925]
Wang Gand Ye A (2007) Possibility of using Zn as the quantum absorber for a laser-cooled neutral atomic optical frequency standard.Phys Rev A76: 1-12 (Article #: 043409). [IF: 2.925]
WangG, Wen C and Ye A (2006) Dynamic holographic optical tweezers using a twisted-nematic liquid crystal display.J Opt A8: 703-708. [IF: 1.742]
