Professor George J. Augustine
Professor of Neuroscience and Mental Health
Principal Investigator, Synaptic Mechanisms and Circuits Laboratory
- Dr Song Sang Ho, PhD, Senior Research Fellow
- Dr Kim Jin Sook, PhD, Research Fellow
- Dr Yoon Su-In, PhD, Research Fellow
- Karen Chung, Research Assistant
- Sarah Kay, Research Assistant
- Chia Zhi Qi, PhD student
Professor George J. Augustine is a Professor in Lee Kong Chian School of Medicine, Nanyang Technological University. He founded the Center for Functional Connectomics at KIST (Seoul, Korea), where he currently serves as Director. He also is a member of the Program in Neuroscience and Behavioral Disorders at the Duke-NUS Graduate Medical School and is a former member of the Department of Neurobiology at the Duke Medical School in the USA, where he was the G.B. Geller Professor of Neurobiology.
Prof Augustine is well-known for his studies of brain synaptic mechanisms His lab has shown that neurotransmitter release is triggered by a remarkably local calcium signal; have identified the roles of many proteins involved in neurotransmitter release; and have identified the role of calcium ions and other chemical signals in transducing brief neuronal activity into long-lasting change in brain function. His group also has developed novel optogenetic technologies and is applying these to study brain circuit function.
He has published nearly 200 articles and has served on the editorial boards of numerous scientific journals, including Neuron, the Journal of Neuroscience, the Journal of Physiology, Frontiers in Neural Circuits, as well as serving as the founding editor of Brain Cell Biology. He also is well-known as a co-author of the highly popular Neuroscience textbook (Sinauer Associates).
One of the most striking features of the brain is the abundant synaptic connections between nerve cells. These connections allow very rapid signalling between nerve cells and serve as the fundamental mechanism for information processing and storage in the brain. Our laboratory is interested in the function of these synaptic connections and we are studying 3 important questions within this general area:
Molecular basis of neurotransmitter release from neurons
The rapid secretion of chemical signals (neurotransmitters) serves as the basis for communication between neurons. We are identifying the proteins that are involved in the synaptic vesicle trafficking reactions underlying neurotransmitter secretion, with particular emphasis on proteins involved in exocytosis and endocytosis. Our current research is largely focussed on the functions of synapsins, a family of proteins whose functions include cross-linking vesicles into a “reserve pool”. The questions we are pursuing include: (1) Why are there so many different synapsin isoforms? and (2) What unique functions do these isoforms serve at different types of synapses?
Signal transduction pathways underlying long-lasting synaptic plasticity
Synaptic signaling is “plastic”, meaning that communication between neurons can get stronger or weaker depending on the previous history of neuronal activity. Such plastic changes in synaptic transmission are thought to be important for dynamic changes in brain function and, in particular, may serve as the basis for memory. We are studying one such form of synaptic plasticity, termed cerebellar long-term synaptic depression (LTD). The questions we are tackling include: (1) What are the signals that initiate LTD? and (2) How does neuronal gene expression change to make LTD permanent?
Optogenetic mapping of brain circuit
Synaptic circuits between neurons form the “wiring” that allows the brain to process information. Optogenetics has revolutionized our ability to elucidate the function of these circuits: with light-activated ion channels, such as channelrhodopsins, we can photostimulate genetically-defined populations of neurons. Likewise, genetically-encoded fluorescent sensors, such as Clomeleon, allow us to detect the resulting responses in postsynaptic neurons. Together, these optogenetic technologies create tremendous opportunities for understanding how the brain works and for determining how brain circuitry goes awry during various neurological and psychiatric diseases. The questions we are addressing are: (1) What is the function of a specific brain circuit? and (2) What is the spatial organization of this circuit? We currently are focusing on circuits in the cerebellum, somatosensory cortex, claustrum, hippocampus, and thalamus.
In these projects, our lab employs a wide range of techniques including electrophysiology, molecular biology, optical microscopy, computational approaches, and optogenetics.
- Berglund, K., Birkner, E., Augustine, G.J. amd U. Hochgeschwender (2013) Light-emitting channelrhodopsins for combined optogenetic and chemical-genetic control of neurons. PLoS One 8, e59759.
- Kim A, Latchoumane C, Lee S, Kim GB, Cheong E, Augustine GJ, Shin HS. (2012) Optogenetically induced sleep spindle rhythms alter sleep architectures in mice. Proc Natl Acad Sci U S A. 109:20673-20678.
- Zhao S, Ting JT, Atallah HE, Qiu L, Tan J, Gloss B, Augustine GJ, Deisseroth, K, Luo M, Graybiel AM, Feng G. (2011) Cell type–specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function. Nature Methods. 8: 745-752.
- Tanaka K, Augustine GJ. (2008) A positive feedback signal transduction loop determines timing of cerebellar long-term depression. Neuron 59:608-20.
- Kuner, T., Y. Li, K.R. Gee, L.F. Bonewald and G.J. Augustine (2008) Photolysis of a caged peptide reveals rapid action of NSF prior to neurotransmitter release. Proc. Natl. Acad. Sci. U.S.A. 105: 347-352.
- Wang H, Peca J, Matsuzaki M, Matsuzaki K, Noguchi J, Qiu L, Wang D, Zhang F, Boyden E, Deisseroth K, Kasai H, Hall WC, Feng G, Augustine GJ. (2007) High-speed mapping of synaptic connectivity using photostimulation in Channelrhodopsin-2 transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 104: 8143-8148.
- Santamaria, F., Wils, S., De Schutter, E. and G.J. Augustine (2006) Anomalous diffusion in Purkinje cell dendrites caused by spines. Neuron 52: 635-648.
- Gitler, D., Y. Takagishi, J. Feng, Y. Ren, R.M. Rodriguiz, W.C. Wetsel, P. Greengard and G.J. Augustine (2004) Different presynaptic roles of synapsins at excitatory and inhibitory synapses. J. Neurosci. 24: 11368-11380.
- Tokumaru, H., L.L. Pelligrini, T. Ishizuka, K. Umayahara, H. Saisu, H. Betz, G.J. Augustine and T. Abe (2001) SNARE complex oligomerization by synaphin/complexin is essential for synaptic vesicle exocytosis. Cell 104: 421-432.
- Finch E.A. and G.J. Augustine (1998) Local calcium signaling by IP3 in Purkinje cell dendrites. Nature 396: 753-756.