·
Dr Sang Ho Song,
PhD, Senior Research Fellow
·
Dr Jin Sook Kim,
PhD, Senior Research Fellow
·
Dr Martin Graf,
PhD, Research Fellow
· Kho Sok Hong, Research Fellow
·
Zach Chia, PhD Student
·
Ham Gao Xiang, PhD
Student
·
Kelly Wong, PhD
Student
·
Minchuan Zhang, PhD Student
·
Aditya Nair,
Undergraduate Student
·
Karen Chung,
Research Assistant
Introduction
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 Programme 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 more than 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. Prof Augustine’s laboratory is interested in the function of
these synaptic connections and they 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. For many years, their lab has identified the
proteins involved exocytosis and endocytosis within presynaptic terminals.
Their current research focuses on the functions of synapsins, a family of
proteins whose functions include cross-linking vesicles into a “reserve pool”.
The questions they 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?
Optogenetic
mapping of brain circuitry
Synaptic
circuits between neurons form the “wiring” that allows the brain to process
information. Optogenetics has revolutionised the 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 SuperClomeleon,
allow Prof Augustine and his team 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 they are addressing are: (1) What is the
function of a specific brain circuit? and (2) What is the spatial organisation
of this circuit? With this approach, they are focusing on circuits in two brain
areas: the cerebellum and the claustrum.
In the
cerebellum, a part of the brain involved in motor coordination and other
functions, they have mapped the functional organization of most local circuits,
as well as projections from cerebellar cortex to other brain areas. Among their
achievements is the discovery of an entirely new type of cerebellar
interneuron. Prof Augustine laboratory’s next goal is to determine the role
that these neurons, and their circuits, play in cerebellar information
processing.
The claustrum
is a mysterious part of the brain that has been proposed to mediate
higher-order functions such as consciousness. To understand the function of the
claustrum, Prof Augustine laboratory’s is employing a “bottom up”
approach. To date, they have classified the intrinsic electrical properties of
all neurons found within the claustrum and have mapped out most of the
local synaptic circuits formed by these neurons. Armed with this knowledge,
their next goal is to examine the role of the claustrum in behaviours.
In these
projects, Prof Augustine’s lab employs a wide range of technologies including
electrophysiology, neuronal cell biology, molecular biology, optical
microscopy, computational approaches, and optogenetics.
Publications
Kim J, Kim Y, ... Augustine GJ, et al. (2017). Inhibitory basal ganglia inputs induce excitatory motor signals in the
thalamus. Neuron. 95:1181-1196.
Chen S, Augustine GJ, & Chadderton P. (2017). Serial processing of kinematic signals by cerebellar circuitry duringvoluntary whisking. Nature Communications. 8:232.
Lo SQ, Sng JCG, & Augustine GJ. (2017). Defining acritical period for inhibitory circuits within the somatosensory cortex. Nature Scientific Reports. 7:7271.
Berglund K, Wen L, ... Augustine GJ (2016). Optogeneticvisualization of presynaptic tonic inhibition of cerebellar parallelfibers. The Journal of Neuroscience. 36:5709-5723.
Song SH & Augustine GJ. (2016). Synapsin isoforms regulating GABA release fromhippocampal interneurons. The Journal of Neuroscience. 36:6742-6757.
Berglund K, Clissold K, ... Augustine GJ, et al. (2016). Luminopsins: integrating opto- and chemogenetics byusing physical and biological light sources for opsin activation. Proceedings of the National Academy of Sciences. 113:E358-67.
Kim J, Lee S, ... Augustine GJ. (2014). Optogeneticmapping of local inhibitory circuitry in cerebellum reveals spatialcoordination of interneurons via electrical synapses. Cell
Reports. 7:1601-1613.
Heiney SA, Kim J, Augustine GJ, et al. (2014). Precise control of movement kinematics by optogeneticinhibition of Purkinje cell activity. The Journal of Neuroscience. 34:2321-2330.
Grimley JS, Li L, ... Augustine GJ. (2013). Visualization of synapticinhibition with an optogenetic sensor developed by cell-free proteinengineering automation. The Journal of Neuroscience. 33:16297-16309.
Asrican B, Augustine GJ, Berglund K, et al. (2013). Next-generation transgenic mice foroptogenetic analysis of neural circuits. Frontiers in Neural Circuits. 7:160.