学 术 报 告----中科院神经科学研究所

中科院神经科学研究所



学 术 报 告

题目：Genetic, Molecular and Functional Analysis
      of Synaptic Transmission in Drosophila



报告人:  Dr Richard W. Ordway  
         Associate Professor
         Department of Biology
         208 Mueller Laboratory
         The Pennsylvania State University



时 间：   2003年3月13日（星期四）
          下午3：00-4：00                                                       





学 术 报 告

题目：The role of glial cells
      in synaptic growth and function



报告人:  Dr Chien-Ping Ko
         Professor
         Section of Neurobiology,
         Department of Biological Sciences
         University of Southern California



时 间：   2003年3月13日（星期四）
          下午4：00-5：00  



地 点： 中科院神经科学所大楼430会议



欢迎各位参加！  


             中科院神经科学研究所
               2003年3月7日

Richard W. Ordway

Ph.D., University of Massachusetts Medical School, 1990



http://www.bio.psu.edu/directory/homepage.asp?username=rwo4



Associate Professor of Biology

Cellular Neurobiology in Drosophila
 
  rwo4@psu.edu





Recent Publications



Drosophila Research at PSU




 
 

As the organ system responsible for controlling our movements, senses, and consciousness, the nervous system must process and transmit information rapidly. To meet this demand, nervous systems utilize networks of nerve cells, each capable of generating electrical impulses and transmitting them to other cells in the network. Understanding the mechanisms underlying the generation and transmission of these impulses is thus essential to understanding fundamental mechanisms of neural function. The focus of our laboratory has been on the mechanisms of signal transmission, specifically those occuring at chemical synapses. Here chemical neurotransmitter is released from the presynaptic neuron and activates the postsynaptic cell membrane. One interesting aspect of this process is the highly regulated and rapid form of exocytosis responsible for neurotransmitter release.

Although the molecular mechanisms underlying neurotransmitter release remain incompletely understood, recent progress has implicated a number of identified proteins. Ideally, the functions of these and other proteins in the release process can be defined by specific perturbation of individual gene products, followed by functional analysis at native synapses in vivo. Our laboratory utilizes the fruit fly, Drosophila melanogaster, as a model experimental system in which synaptic mechanisms similar to those of vertebrates can be studied in vivo, using a powerful combination of genetic, molecular, biochemical, electrophysiological and ultrastructural approaches. Genetic methods are used to screen for mutants defective in synaptic transmission; molecular and biochemical methods are used to identify, characterize, and manipulate the affected protein; and electrophysiological and ultrastructural methods are used to investigate the in vivo function of the protein at native synapses.







Ongoing projects include the analysis of temperature-sensitive (TS) paralytic mutants exhibiting conditional defects in synaptic transmission. These conditional mutants allow normal development and function at permissive temperature, while also allowing acute perturbation of a specific gene product in the mature animal. These features make TS paralytic mutants a unique and powerful tool for analyzing the in vivo physiological functions of specific proteins.  One example is our analysis in  comatose mutants (see Figure), in which paralysis results from a TS defect in a Drosophila N-ethylmaleimide sensitive fusion protein (NSF). Our functional analysis, together with biochemical analysis in comatose [Tolar and Pallanck (1998) Journal of Neuroscience 18(24):10250-10256] have defined the function of this NSF protein in regulated exocytosis of neurotransmitter. Subsequently we have extended our analysis by analyzing TS mutations affecting other key components of the neurotransmitter release apparatus. For example we have isolated a TS allele of the cacophony gene, which encodes the primary structural subunit of a voltage-gated calcium channel, and have utilized this mutant to demonstrate that cacophony encodes a primary synaptic calcium channel functioning in neurotransmitter release. Further detailed analysis of TS mutations alone and in combination promises to provide new insights into the in vivo functions and interactions of specific gene products in synaptic transmission.
 

Recent Publications




 

Brooks, I.M., Felling, R., Kawasaki, F. and R.W. Ordway (2003) Genetic analysis of a synaptic calcium channel in Drosophila: Intragenic modifiers of a temperature-sensitive paralytic mutant of cacophony. Genetics (in press).
 

Kawasaki, F., Collins, S.C. and R.W. Ordway (2002) Synaptic calcium channel function in Drosophila: Analysis and transformation rescue of temperature-sensitive paralytic and lethal mutations of cacophony. J. Neuroscience 22: 5856?864.
   

Kawasaki, F., Hazen, M., and R.W. Ordway (2000) Fast synaptic fatigue in shibire mutants reveals a rapid requirement for dynamin in synaptic vesicle membrane trafficking. Nature Neuroscience 3:859-860.
   

Kawasaki, F., Felling, R., and R.W. Ordway, (2000) A temperature-sensitive paralytic mutant defines a primary synaptic calcium channel in Drosophila. J. Neuroscience 20:4885-4890.
 

Dellinger, B.B., Felling, R., and R.W. Ordway,  (2000) Genetic modifiers of the Drosophila NSF mutant, comatose, include a temperature-sensitive paralytic allele of the calcium channel a1 subunit gene, cacophony.  Genetics 155:203-211

Kawasaki, F. and R.W. Ordway. (1999) The Drosophila NSF protein, dNSF1, plays a similar role in neurotransmitter release at neuromuscular and some central synapses. J. Neurophysiology 82:123-130.



Kawasaki, F.,  Mattiuz, A.M., and R.W. Ordway. (1998) Synaptic physiology and ultrastructure in comatose mutants defines an in vivo role for NSF in the neurotransmitter release. J. Neuroscience 18:10241-10249.



Pallanck, L., Ordway, R.W.,  Ramaswami, M., Chi, W.Y., Krishnan, K. S., and B. Ganetzky. (1995) Distinct roles for N-ethylmaleimide sensitive fusion protein (NSF) suggested by the identification of a second Drosophila NSF homolog. J. Biol. Chem. 270:18742?8744.



Pallanck, L., Ordway, R.W., and B. Ganetzky.  (1995) A Drosophila NSF mutant. Nature 376:25.



Ordway, R.W., Pallanck, L., and  B. Ganetzky. (1994) A TPR domain in the SNAP secretory proteins. Trends Biochem. Sci. 19:530?31.



Ordway, R.W., Pallanck, L., and B. Ganetzky. (1994) Neurally expressed Drosophila genes encoding homologs of the NSF and SNAP secretory proteins. Proc. Nat. Acad. Sci.  91:5715?719.





Search the MEDLINE database at PubMed for articles by Articles by R. W. Ordway.  

 Chien-Ping Ko
  Professor, Department of Biological Sciences

Director / Associate Director, Center for Electron Microscopy and Microanalysis

Editorial Board, Journal of Neurocytology  

Contact Information for Chien-Ping Ko

Research Group
 



Synapse formation, sprouting, remodeling and maintenance, synaptic transmission, synapse-glial interactions, neuromuscular junction, Schwann cells, acetylcholine receptor aggregation, nerve regeneration.
 





--------------------------------------------------------------------------------

Research

I am interested in cellular and molecular mechanisms of synaptic function, regeneration, development, remodeling, and maintenance. My current research focuses on the role of the perisynaptic Schwann cell (PSC) and synapse-glial interactions at a prototype synapse, the neuromuscular junction.



Although the PSC, which caps the nerve terminal, is an integral component of the neuromuscular junction, remarkably little is known about the function of this synapse-associated glial cell. We have used peanut agglutinin and several novel monoclonal antibodies generated in my laboratory to label the extracellular matrix or surface membrane of PSCs. We have shown that PSCs sprout cellular processes profusely following nerve injury and regeneration in adult frog muscles, and during the initial stages of synaptogenesis in tadpole muscles. We have revealed in vivo that PSC sprouts lead nerve terminal extension during synaptic sprouting, regeneration, and development. These results suggest that PSCs may guide nerve terminal outgrowth and synapse formation. We have also found that adult Schwann cells express active isoforms of agrin and neuregulin, and play a role in the aggregation and synthesis of acetylcholine receptors on muscle fibers. Recently, we have developed a novel technique using complement-mediated lysis to selectively ablate PSCs in vivo. This technique would allow us to investigate whether and how PSCs play a role in synaptic modulation, sprouting, maintenance, and development of the neuromuscular junction. In addition, we are interested in the role of glial-derived factors in promoting synaptic function and formation. Our research on synapse-glial interactions would test an emerging concept that glial cells tell neurons to build larger, stronger and more stable synapses



Another area of my research interest is in the active zone (site of transmitter release) in relation to voltage-sensitive calcium channels at the neuromuscular junction. We are also interested in using transgenic or knockout mice to investigate the role of key synaptic molecules in function, formation and maintenance of the mammalian neuromuscular junction.



The techniques used in my laboratory include intracellular recording, patch-clamp, fluorescence microscopy, video and confocal microscopy, electron microscopy, immunocytochemistry, monoclonal antibody production, affinity chromatography, PCR, immunoblotting, and tissue culture.


 
 
 

Selected Publications

Generate PubMed search for publications by C.-P. Ko



Brandon, E. P., Lin, W., D’Amour, K. A., Pizzo, D. P., Dominguez, B., Sugiura, Y., Thode, S., Ko, C.-P., Thal, LJ, Gage, FH, and Lee, K.-F. Aberrant patterning of neuromuscular synapses in choline acetyltransferase deficient mice. The Journal of Neuroscience, 23:539-549 (2003).



Yang, J.-F., Cao, G, Koirala, S., Reddy, LV. and Ko, C.P. Schwann cells express active agrin and enhance acetylcholine receptor aggregation on muscle fibers. The Journal of Neuroscience, 21:9572-9584 (2001).



Herrera AA, Qiang H, Ko CP. The role of perisynaptic Schwann cells in development of neuromuscular junctions in the frog (Xenopus laevis). Journal of Neurobiology, 45:237-254 (2000).



Koirala S, Qiang H, Ko CP. Reciprocal interactions between perisynaptic Schwann cells and regenerating nerve terminals at the frog neuromuscular junction. Journal of Neurobiol, 44:343-360 (2000).



Astrow, S. H., Qiang, H. and Ko, C.-P. Perisynaptic Schwann cells at the neuromuscular junctions revealed by a novel monoclonal antibody. Journal of Neurocytology, 27:667-681 (1998).



Sugiura, Y. and Ko, C.-P. Novel modulatory effect of L-type calcium channels at newly-formed neuromuscular junctions. The Journal of Neuroscience, 17:1101-1111 (1997).



Ko, C.-P. and Chen, L. Synaptic remodeling revealed by repeated, in vivo observations and electron microscopy of identified frog neuromuscular junctions. The Journal of Neuroscience, 16:1780-1790 (1996).
 
 

Education

B.S., National Taiwan University, 1970.

Ph.D., Washington University in St. Louis, 1975.

Post-Doctoral, University of Colorado Medical Center, 1978.

Post-Doctoral, National Institutes of Health, 1981.


 
 
 

Contact Information

University of Southern California

Department of Biological Sciences

3614 Watt Way HNB 209

Los Angeles, CA 90089-2520



Office Phone: (213) 740-9182

Fax: (213) 740-5687
 cko@usc.edu



Office Location: HNB 209



Lab Location: HNB 209



Lab Phones: (213) 740-9179
 
 http://www.usc.edu/dept/nbio/ngp/Faculty/ko-cp.shtml

有个疑问，中科院各所的学术报告是否只对所内人员开放，不对其它外高校院所开放？[em15]

有没有详细内容可以下载？