Speaker: Yi Rao
School of Life Science, PekingUniversity
Time:20:00p.m. , Nov. 7th, 2009
Research Description: We have two major lines of research: the molecular studies of neuronal polarity in mammals and genetic analysis of social behavior.Polarity is a basic cellular feature. Each neuron usually has an axon and multiple dendrites, each of which play different roles: axons usually send signals and dendrites receive them. Abnormalities in neuronal polarity disrupt informational flow in the nervous system. Molecular and subcellular studies of neuronal polarity will contribute to our understanding of the basic mechanisms and may also suggest new approaches to facilitate recovery after neural injuries. Our lab currently focuses on signal transduction pathways involved in establishing and maintaining neuronal polarity.
We take genetic approaches to study social behavior in Drosophila and mice. Our focus is on aggression among members of the same sex, courtship between members of the opposite sex and parental behavior between members of different generations. We use quantifiable behavioral paradigms to observe behaviors and their changes. Genetic manipulations allow us to control neuronal activities in defined regions, which make it possible to determine brain regions involved in a specific behavior. Analysis of behavioral phenotype of genetic mutations allows us to discover molecules underlying behaviors. We hope to understand the molecules and neural pathways involved in behavior and the molecular and cellular mechanisms required for the development of behaviors.
Leica Lecture on Neuroscience
Reverse engineering the brain: what tools do we need?
Speaker: Winfried Denk
8:30a.m. , Nov. 8th, 2009
This department's goal is the development and application of new optical methods for biomedical research. Biological function occurs often in a complex tissue environment and ultimately has to be studied in that context. Optical microscopy is virtually the only means by which living tissue can be studied with high spatial resolution. While the concept of optical microscopy per se is a rather dated one, going back several centuries, a number of developments over the last several decades have lead to a return of the light microscope to the front-lines of biological research. Among those are the development of efficient non-toxic fluorophores together with highly sensitive means of fluorescence detection, optical sectioning microscopy, photochemical activation (uncaging) of signal substances, and the discovery and subsequent optimization of genetically encodable fluorophores (GFP and its variants).
Mitochondrial transport and its impact on synaptic plasticity, axonal homeostasis, and neuronal degeneration
Speaker: Zu-Hang Sheng
NINDS, NIH, USA
8:00a.m. , Nov. 9th, 2009
The formation of new synapses or remodeling of existing synapses requires the targeted delivery of synaptic components. Presynaptic components, including active zone (AZ) precursors, mitochondria, and proteins responsible for the assembly of synaptic vesicle (SV) fusion machines, are transported to the nerve terminal by kinesin motors moving along microtubules. Upon arrival at the terminal, cargo-loaded transport vesicles undergo fusion with the plasma membrane to assemble AZs and to recruit SVs. Docked and primed SVs are then available for exocytosis in response to a rise in intracellular [Ca2+] triggered by the opening of voltage-gated Ca2+ channels. Proper synaptic function requires the tight coordination of these processes.
Our long-term research goals aim to elucidate molecular and cellular mechanisms underlying (1) the axonal transport of synaptic components and organelles essential for the assembly of synapses and activity-dependent presynaptic plasticity; and (2) the regulation of SV priming for fusion. Such mechanisms are crucial for the initial establishment of presynaptic terminals and for the modulation of synaptic function. Using a combination of state-of-the-art live cell imaging, molecular biology, biochemistry, cell biology, and electrophysiology, we have identified three new proteins named Snapin, syntaphilin, and syntabulin. With the generation of knockout mice, the physiological roles of Snapin in priming SV for fusion and syntaphilin in controlling the motility of axonal mitochondria are being revealed. Using live cell imaging combined with multiple loss-of-function approaches we are providing a critical assessment of syntabulins role in the trafficking of AZ components for the assembly of presynaptic terminals and for the activity-dependent synaptic plasticity. We will continue to combine our effective approaches using multi-disciplinary systems analysis of genetically engineered mice. Our studies will yield fundamental information that may have an impact on the understanding of neurodegenerative disorders with defective trafficking processes.
Synaptic adhesion molecules and synaptogenesis
Speaker: Eunjoon Kim
Korea Advanced Institute of Science and Technology, Korea
8:00a.m. , Nov. 10th, 2009
Glutamate receptors mediate the majority of excitatory synaptic transmissions in the brain and are associated with brain development, learning/memory, and various brain diseases including schizophrenia. Recently reported NR2B (a subunit of NMDA glutamate receptor)-overexpressing smart mice and NR1 (another subunit of NMDA receptor)-lacking schizophrenic mice are clear examples of the importance of glutamate receptors.
An important aspect of neuronal synapses is their plasticity. The number of synapses and the efficiency of synaptic transmission undergo plastic changes. The synaptic plasticity is a key mechanism underlying the regulation of neural network in the brain, determining simple brain functions (perception, learning and memory) as well as complex brain functions such as analysis, decision making, and creativity. The synaptic plasticity is also keenly associated with various brain dysfunctions. The number of synapses is dramatically reduced in the brain of schizophrenic patients as well as in normally aging brains. The drastic reduction in the number of synapses is also observed in brains of human patients suffering from conditions associated with mental retardation including down syndrome, fragile X syndrome, fetal alcohol syndrome. The list of synapse-related brain diseases has been rapidly growing in recent years.
Previous studies on the synaptic plasticity have been performed mainly using biochemical and electrophysiological tools. However, recent works have identified that neuronal synapses undergo very dynamic and rapid ‘structural’ changes.
In exploration of the structural plasticity of neuronal synapses, the following four critical questions need to be addressed.
1. What are the major building blocks of neuronal synapses?
2. How do these building blocks assemble into functional neuronal synapses?
3. How is the assembly of synaptic proteins regulated?
4. How is the structural plasticity of synapses related to functional plasticity?
5. What is the relationship between structural and functional plasticity of synapses and various brain functions and dysfunctions?
In this context, synaptic proteins of high interest are the molecules that are directly or indirectly associated with glutamate receptors. They link glutamate receptors to various signaling and cytoskeletal proteins, leading to the formation of a postsynaptic multiprotein complex known as the postsynaptic density (PSD). The PSD functions as a site of integration for postsynaptic signaling as well as a scaffold for the formation and maintenance of neuronal synapses. Naturally the PSD is very plastic and undergoes rapid structural and functional changes in an activity-dependent manner. Molecular mechanisms underlying synaptic plasticity are under intense investigation worldwide including this laboratory.
Representation of object categories in activity patterns of inferotemporal cell population
Speaker: Keiji Tanaka
15:15p.m. , Nov. 8th, 2009
To reveal mechanisms of higher brain functions such as recognition and decision making, we are conducting experiments with non-human primates and functional MRI with a 4T system on normal human subjects. In the research with non-human primates, the animals are trained with various behavioral paradigms, and single-cell recordings are conducted from the prefrontal and inferotemporal association cortical areas during the task performance. We are focusing on the mechanisms of visual object recognition in the inferotemporal cortex and those of goal-directed behavior in the prefrontal cortex. To relate research results in human subjects with those in experimental animals, we are also making efforts to increase the spatial resolution of fMRI with human subjects.
(1) Mechanisms of visual object recognition
(2) Mechanisms of goal-directed behavior
(3) fMRI of functional architectures in human cortex
Networks in motion-from ion channels to motor behavior
How a Nobel Laureate Is Selected?
Speaker: Sten Grillner
Karolinska Institute, Sweden
20:00p.m. , Nov. 9th, 2009
Research Focus: Our main aim is to understand the cellular bases of motor behaviour with a focus on the mechanisms underlying selection of behaviour and the neural bases of in particular locomotion, posture, orienting and eye movements. This in turn requires a detailed knowledge of which nerve cells take part, how they talk to each other through synaptic interaction and an understanding of the intrinsic function of these networks. The properties of the nerve cells within the network can vary greatly and are determined by the palette of ion channels expressed and also other gene products. Essentially our research extends from ion channels and synapses to network mechanisms and behaviour utilizing a multitude of techniques from patch clamp and cellular imaging to modelling and studies of behaviour. We utilize preferentially the lamprey as model organism but also mammalian models for the studies of posture and selection mechanisms.
We have been able, based on detailed cellular knowledge, to successfully model the networks responsible for the command and pattern generating systems for locomotion including steering and posture. Our work continues with several foci including the role of the basal ganglia for selection of different patterns of motor behaviour, tectum for steering and eye motor coordination, the physiological role of different modulator systems acting through the spinal networks, and different ion channel subtypes contributing to neuronal function.
Cultural influences on neural substrates of human cognition
Speaker: Shihui Han
14:30p.m. , Nov. 8th, 2009
The human brain develops in social contexts. The cognitive functions of the brain are greatly influenced by the interaction between an individual and the environment. The Culture and Social Cognitive Neuroscience Laboratory investigates whether and how social interaction and shared knowledge modulate human brain functions using varieties of neuroimaging methods including high density event related brain potentials (ERPs), functional magnetic resonance imaging (fMRI), and transcranial magnetic stimulation (TMS). We study cultural and social effects on the neural mechanism underlying low- and high-level cognitive brain functions. For example, we investigate whether perceptual processing (such as global/local processing of hierarchically organized visual stimuli) and spatial attention are modulated by cultural priming. We also investigate neural substrates underlying processing of social information. Specifically, we study how human brains perceive emotion, intention, and belief by observing others' behaviors in complex visual scenes, how the brain represents the self, how cultures influence neural substrates of self representation, and how cognitive and neural mechanisms mediating processes of social signals develop with age. Our research is conducted on both healthy adults and patients with brain lesions.
Our research projects include:
Bottom-up and top-down mechanisms of empathy for pain;
Cultural influence on self-recognition and self-representation;
Domain general and domain specific neural mechanisms of theory-of-mind;
Cultural influence on neural mechanisms of causal attribution.
The TRPC6 channels and neuronal survival
15:15p.m. , Nov. 9th, 2009
Apoptosis occurs during development and may contribute to numerous pathological conditions, including stroke, spinal cord injury, and certain neurodegenerative diseases. Although the molecular mechanism of apoptosis has been extensively investigated, how apoptosis is induced in neurons under pathological conditions, such as stroke, remains largely unknown. Our group has been studying the mechanism of neuronal cell death at molecular and cellular levels, focusing on the role of intracellular ions and their channels in neuronal apoptosis.
Activation of ion channels and subsequent stimulation of protein kinase cascades affect neuronal survival. Our ongoing research includes study of the roles and mechanisms of transient receptor potential (TRP) C channels and K+ channels in neuronal survival, differentiation and cell proliferation. A variety of methods including molecular biology, cellular biology, biochemistry and electrophysiology are employed to investigate the mechanisms by which these channels affect cell survival in the models of primary neuronal cultures, cell lines as well as whole animals. Together, the successful outcome of our studies may have important implications in both furthering the understanding of neuronal survival mechanisms and therapeutics pertinent to neuronal cell death.
Axons, dendrites, and synapses: Molecular control of neuronal connectivity
Speaker: Anirvan Ghosh
14:30p.m. , Nov. 9th, 2009
Anirvan Ghosh received his Ph.D. in Neuroscience at StanfordUniversity and completed his postdoctoral studies at HarvardMedicalSchool in Molecular Neuroscience. He was on the faculty at John Hopkins University School of Medicine prior to moving to University of California, San Diego as the Stephen Kuffler Professor of Biology. He is currently chair of the Neurobiology Section and the Director of the UCSD/Salk Neurosciences Graduate Program.
Professor Ghosh has received numerous honors including the Alfred P. Sloan Research Fellow, the Pew Scholar Award, the Presidential Early Career Award for Scientists and Engineers, and the Society for Neuroscience Young Investigator Award. Recently Dr. Ghosh was awarded a grant from the California Institute for Regenerative Medicine to generate forebrain neurons from human ES cells and The Outstanding Faculty Award from RevelleCollege at UCSD.
The primary focus of research in Professor Ghosh’s lab is directed at understanding how the brain wires itself during development. His research interests include the identification of genes that regulate neuronal connectivity, and the influence of activity and sensory experience on the development of neural circuits.
A novel therapeutic strategy for stroke-opening calcium channels
Speaker: Tian-Ming Gao
14:30p.m. , Nov. 10th, 2009
Tian-Ming Gao, M.D., Ph.D.
Research Focus: Stroke is the third leading cause of death and number one cause of disability around the world.The loss of neurological functions following stroke is caused by massive loss of neurons resulting from ischemic insults. Neurons in certain regions of the brain (e.g. CA1 pyramidal neurons in hippocampus and pyramidal neurons in layers 3,5 and 6 of the neocortex) are highly vulnerable to cerebral ischemia.The mechanisms of such selective cell death following ischemia remain unknown and at present there is no any neuroprotective drug to be used in clinic.The long-term goal of this laboratory is to reveal the mechanisms of neuronal damage following cerebral ischemia and provide basis for developing therapeutical interventions.
The current projects of this laboratory are: 1) investigating the role of ion channels and its intracellular signaling pathways in the ischemic neuronal damage, 2) screening new proteins and microRNAs involved in the ischemic neuronal damage, and 3) exploring the physical and chemical ways to activate endogenous neuronal stem cells for repairing ischemic neuronal damage in cell culture and animal models.The research techniques include: intracellular recording and staining in vivo and in vitro; patch-clamped whole-cell or single channel recording in brain slices and dissociated cells, calcium imaging, proteomics, microRNA chip, western blot, immunoprecipitation, immunocytochemistry, real time PCR, in situ hybridization, light and electron microscopy, siRNA, gene transfection, animal behavior testing, etc.