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>Home >FACULTY> Chih-Tien Wang, Associate Professor
Chih-Tien Wang, Associate Professor
 
Associate Professor

Born in 1970

Ph. D. , University of Wisconsin-Madison , U.S.A.
Postdoctoral Scholar , University of Wisconsin-Madison, U.S.A.
Postdoctoral Scholar , University of California, San Diego, U.S.A.

Specialty: Neurotransmitter release; Neural circuit development

E-mail : chihtienwang @ntu.edu.tw

Laboratory: Life Science Building R1010

TEL 886-2- 33662484 FAX 886-2-33662478

Recent Research Topics
  • Molecular mechanisms underlying neurotransmitter release and neural circuit development

Laboratory: Molecular Neurobiology Laboratory

The fundamental question in the field of neuroscience is how neurons in the circuits communicate with one another. In our lab, we are interested in studying how neurotransmitters are released to affect nearby neurons and how the precise neural circuits are established during development.

First, we adapt a neuroendocrine cell line (PC12 cells) as a model system to delineate the structure-functional relationship of specific proteins mediating Ca 2+ -regulated exocytosis, which leads to neurotransmitter release. The sequential steps in Ca 2+ -regulated exocytosis have been resolved at the single-vesicle level by amperometry recordings. Our research interest has converged on the fusion pore, a critical kinetic intermediate in Ca 2+ -regulated exocytosis. We have identified that phosphorylation of various synaptic proteins regulates the dynamics of exocytotic fusion pore, through the action of multiple kinases. These results provide the first evidence that post-translational modification of synaptic proteins is sufficient to rapidly regulate fusion pore dynamics, accounting for the impact of rapid switch in cellular signalings on the kinetics of neurotransmitter release.

Second, we aim to study the molecular mechanisms underlying neurotransmitter release from mature neurons in the central nervous system. A novel in vivo electroporation technique has been established in our laboratory to deliver genes of interest into the hypothalamic-neurohypophysial system (HNS). The HNS serves as a good system to study the release mechanism of neuropeptides (oxytocin and vasopressin) from axonal sites (posterior pituitary nerve terminals) or somatodendritic sites (magnocellular neurons). This new technique provides us a powerful tool to elucidate the secretion in the HNS at molecular, cellular, network, and animal levels.

Third, we employ the developing rodent retina as a model system to study neural circuit development. During a developmental critical period, the spontaneous bursts of action potentials fire periodically and propagate across a population of developing retinal neurons to refine the visual circuits, termed as “retinal waves”. However, why and how retinal waves occur remains mysterious. To further elucidate why retinal waves occur during the critical period of retinal circuit refinement, we use single-cell reverse-transcriptase quantitative PCR (sc RT-qPCR) to determine the profile of gene expression. We test the hypothesis if the firing patterns of retinal waves encode the information for gene expression in establishment of neural circuits. Our ultimate goal is to identify which patterns of retinal waves encode the information for the precise connections between retinas and their central brain targets. In addition, we have identified that the spatiotemporal patterns of retinal waves are modulated by a number of synaptic proteins in the wave-initiating neurons. Thus, the modulation of retinal wave patterns is associated with the kinetics of neurotransmitter release from presynaptic neurons. Elucidating the molecular mechanisms underlying retinal waves will provide us the insight into the general mechanisms by which the precise circuits are formed during neural development.

 

Selected Research Publications

Journal Articles: (* corresponding author)

1. Chih-Tien Wang , Ruey-Ling Huang, Mei-Yun Tai, Yuan-Feen Tsai and Ming-Tsung Peng. Dopamine release in the nucleus accumbens during sexual behavior in prenatally stressed adult male rats. Neuroscience Letters. 1995 Nov 10; 200(1): 29-32.

2. Ruey-Ling Huang, Chih-Tien Wang , Mei-Yun Tai, Yuan-Feen Tsai and Ming-Tsung Peng. Effects of age on dopamine release in the nucleus accumbens and amphetamine-induced locomotor activity in rats. Neuroscience Letters. 1995 Nov 10; 200(1): 61-4.

3.  Chih-Tien Wang , Hai-Guang Zhang, Thomas A. Rocheleau, Richard H. ffrench-Constant and Meyer B. Jackson. Cation permeability and cation-anion interactions in a mutant GABA-gated chloride channel from Drosophila. Biophysical Journal. 1999 Aug; 77(2): 691-700.

4.  Chih-Tien Wang , Rusland Grishanin, Cynthia A. Earles, Payne Y. Chang, Thomas F. J. Martin, Edwin R. Chapman and Meyer B. Jackson. Synaptotagmin modulation of fusion pore kinetics in regulated exocytosis of dense-core vesicles. Science. 2001 Nov 2; 294(5544): 1111-5.

5.  J. Michael Edwardson, Chih-Tien Wang , Belvin Gong, Andreas Wyttenbach, Jihong Bai, Meyer B. Jackson, Edwin R. Chapman and A. Jennifer Morton. Expression of mutant huntingtin blocks exocytosis in PC12 cells by depletion of complexin II. Journal of Biological Chemistry. 2003 Aug 15; 278(33): 30849-53.

6.  Chih-Tien Wang , Juu-Chin Lu, Jihong Bai, Payne Y. Chang, Thomas F. J. Martin, Edwin R. Chapman and Meyer B. Jackson. Different domains of synaptotagmin control the choice between kiss-and-run and full fusion. Nature. 2003 Aug 21; 424(6951): 943-7.

7.  Ping Wang, Chih-Tien Wang , Jihong Bai, Meyer B. Jackson and Edwin R. Chapman. Mutations in the effector binding loops in the C 2A and C2B domains of synaptotagmin I disrupt exocytosis in a nonadditive manner. Journal of Biological Chemistry. 2003 Nov 21; 278(47): 47030-7.

8.  Jihong Bai, Chih-Tien Wang , David A. Richards, Meyer B. Jackson and Edwin R. Chapman. Fusion pore dynamics are regulated by synaptotagmin*t-SNARE interactions. Neuron. 2004 Mar 25; 41(6): 929-42.

9.  Xue Han, Chih-Tien Wang , Jihong Bai, Edwin R. Chapman and Meyer B. Jackson. Transmembrane segments of syntaxin line the fusion pore of Ca 2+ -triggered exocytosis. Science. 2004 Apr 9; 304(5668): 289-92.

10.  Christine Torborg, Chih-Tien Wang , Gianna Muir-Robinson and Marla B. Feller. L-type calcium channel agonist induces correlated depolarizations in mice lacking the b 2 subunit nAChRs. Vision Research. 2004 Dec; 44(28): 3347-55.

11.  Sally I. Firth, Chih-Tien Wang and Marla B. Feller. Retinal waves: Mechanisms and function in visual system development. Cell Calcium. 2005 Apr 9; 37: 425-32.

12.  Chih-Tien Wang 1 , Hao-Ai Shui 1 , Ruey-Ling Huang, Mei-Yun Tai, Ming-Tsung Peng and Yuan-Feen Tsai. Sexual motivation is demasculinized, but not feminized, in prenatally stressed male rats. Neuroscience. 2006 Jan 4;138(2):357-64. ( 1 These authors contributed equally.)

13.  Chih-Tien Wang , Jihong Bai, Payne Y. Chang, Edwin R. Chapman and Meyer B. Jackson. Synaptotagmin*calcium triggers two sequential steps in regulated exocytosis in rat PC12 cells: Fusion pore opening and fusion pore dilation. Journal of Physiology ( London ). 2006 Jan 15;570(Pt 2):295-307.

14.  Timothy A. Dunn 1 , Chih-Tien Wang 1 , Michael A. Colicos, Manuela Zaccolo, Lisa M. DePilato, Jin Zhang, Roger Y. Tsien and Marla B. Feller. Imaging of cAMP levels and protein kinase A activity reveals that retinal waves drives oscillations in second- messenger cascade. The Journal of Neuroscience. 2006 Dec 6; 26(49): 12807-15. ( 1 These authors contributed equally.)  

15.  Chih-Tien Wang , Aaron G. Blankenship, Anastasia Anishchenko, Justin Elstrott, Michael Fikhman, Shigetada Nakanishi and Marla B. Feller. GABA A receptor-mediated signaling alters the structure of spontaneous activity in the developing retina. The Journal of Neuroscience. 2007 Aug 22; 27(34): 9130-40.

15.  Chih-Tien Wang , Aaron G. Blankenship, Anastasia Anishchenko, Justin Elstrott, Michael Fikhman, Shigetada Nakanishi and Marla B. Feller. GABA A receptor-mediated signaling alters the structure of spontaneous activity in the developing retina. The Journal of Neuroscience. 2007 Aug 22; 27(34): 9130-40.

16.  Chung-Wei Chiang, Yu-Chieh Chen, Juu-Chin Lu, Yu-Tien Hsiao, Che-Wei Chang, Pin-Chien Huang, Yu-Tzu Chang, Payne Y. Chang and Chih-Tien Wang* . Synaptotagmin I regulates patterned spontaneous activity in the developing rat retina via calcium binding to the C2AB domains. PLoS ONE. 2012 Oct 16; 7(10):e47465.

17.  Juu-Chin Lu, Yu-Tzu Chang, Chih-Tien Wang , Yu-Chun Lin, Chun-Ken Lin and Zhong-Sheng Wu. Trichostatin A modulates thiazolidinedione-mediated suppression of tumor necrosis factor a -induced lipolysis in 3T3-L1 adipocytes. PLoS ONE. 2013 Aug 9; 8(8):e71517.

18.  Juu-Chin Lu, Yu-Tien Hsiao, Chung-Wei Chiang and Chih-Tien Wang* . GABA A receptor-mediated tonic depolarization in the developing neural circuits. Molecular Neurobiology. 2014 Mar 14; 49: 702-23.  

19.  Pin-Chien Huang, Yu-Tien Hsiao, Shao-Yen Kao, Ching-Feng Chen, Yu-Chieh Chen, Chung-Wei Chiang, Ching-fei Lee, Juu-Chin Lu, Yijuang Chern and Chih-Tien Wang* . Adenosine A 2 A r eceptor up-regulates retinal wave frequency via starburst amacrine cells in the d eveloping rat retina . PLoS ONE. 2014 Apr 28; 9(4): e95090.

20.  Ning Chiang, Yu-Tien Hsiao, Hui-Ju Yang, Yu-Chun Lin, Juu-Chin Lu* and Chih-Tien Wang* . Phosphomimetic mutation of cysteine string protein- a increases the rate of regulated exocytosis by modulating fusion pore dynamics in PC12 cells. PLoS ONE. 2014 Jun 23; 9(6): e99180.

International Conference Abstracts: (*corresponding author)

1.  Chih-Tien Wang , Ruey-Ling Huang, Mei-Yun Tai, Yuan-Feen Tsai and Ming-Tsung Peng. Sexual motivation and dopamine activity in the nucleus accumbens of prenatally stressed male Rats: An in vivo microdialysis study, Fourth IBRO World Congress of Neuroscience (9-14 July 1995, Kyoto , Japan ).

2.  Chih-Tien Wang , Hai-Guang Zhang, Thomas A. Rocheleau, Richard H. ffrench-Constant and Meyer B. Jackson. Cation permeability and a Drosophila GABA-activated chloride channel with a mutation in the extracellular ring, Biophysical Journal , Vol.72, No. 2, A41, 1997.

3.  Chih-Tien Wang , Cynthia A. Earles, Rusland Grishanin, Payne Y. Chang, Thomas F. J. Martin, Edwin R. Chapman and Meyer B. Jackson. Fusion pore dynamics regulated by synaptotagmin, The 31 st Annual Meeting of the Society for Neuroscience (10-15 November 2001, San Diego , CA ).

4.  Chih-Tien Wang , Juu-Chin Lu, Edwin R. Chapman, Thomas F. J. Martin, and Meyer B. Jackson. Synaptotagmin IV induces long-duration kiss-and-run exocytosis through small fusion pores, Biophysical Journal , Vol.84, No. 2, 209a , 2003.

5.  Chih-Tien Wang , Thomas F. J. Martin, Edwin R. Chapman, and Meyer B. Jackson. Calcium regulation of fusion pore dynamics with different synaptotagmin isoforms, The 33 rd Annual Meeting of the Society for Neuroscience (8-12 November 2003, New Orleans , LA ).

6.  Chih-Tien Wang and Marla B. Feller. Adenosine modulates the excitability of ganglion cells in the developing rat retina, The 34 th Annual Meeting of the Society for Neuroscience (23-27 October 2004, San Diego , CA ).

7.  Chih-Tien Wang and Marla B. Feller. Dual mechanisms underlying adenosine regulation of spontaneous activity in the developing rat retina, The 35 th Annual Meeting of the Society for Neuroscience (12-16 November 2005, Washington , D.C. ).

8.  Timothy A. Dunn, Chih-Tien Wang , Jin Zhang, Roger Y. Tsien and Marla B. Feller. Imaging of PKA activity transients in the developing mammalian retina, The 35 th Annual Meeting of the Society for Neuroscience (12-16 November 2005, Washington , D.C. ).

9.  Yu-Tien Hsiao, Che-Wei Chang, Ming-Han Hsu, Ning Chiang and Chih-Tien Wang* . Fusion pore dynamics regulated by cyclic AMP, The 39 th Annual Meeting of the Society for Neuroscience (17-21 October 2009, Chicago , IL , U.S.A. ).

10.  Chia-Wei Kao, Che-Wei Chang, Ning Chiang, Ming-Han Hsu, Wei-Chun Wang and Chih-Tien Wang* . Delivery of synaptotagmin genes into the hypothalamus-posterior pituitary system by in vivo electroporation, The 39 th Annual Meeting of the Society for Neuroscience (17-21 October 2009, Chicago , IL , U.S.A. ).

11.  Chung-Wei Chiang, Che-Wei Chang, Yu-Chieh Chen, Ming-Han Hsu, and Chih-Tien Wang* . Presynaptic synaptotagmin regulates retinal waves in developing rat retinas, The 39 th Annual Meeting of the Society for Neuroscience (17-21 October 2009, Chicago , IL , U.S.A. ).

12.  Yu-Tien Hsiao, Ning Chiang and Chih-Tien Wang* . Phosphorylation of SNAP-25 regulates dynamics of exocytotic fusion pore, The 40 th Annual Meeting of the Society for Neuroscience (12-17 November 2010, San Diego , CA , U.S.A. ).

13.  Chia-Wei Kao, Hsin-I Jen, Ting-Yu Lai, Li-Chung Hsu and Chih-Tien Wang* . Targeting of synaptotagmin proteins from supraoptic nucleus to posterior pituitary after in vivo electroporation, The 40 th Annual Meeting of the Society for Neuroscience (12-17 November 2010, San Diego , CA , U.S.A. ).

14.  Pin-Chien Huang, Yu-Chieh Chen, and Chih-Tien Wang* . G-protein coupling with adenosine A 2A receptor regulates retinal waves in developing rat retinas, The 40 th Annual Meeting of the Society for Neuroscience (12-17 November 2010, San Diego , CA , U.S.A. ).

15.  Hsin-I Jen, Ching-Hsun Huang, Chia-Wei Kao, Ming-Han Hsu, Wen-Sung Lai and Chih-Tien Wang* . Synaptotagmin IV in supraoptic nucleus modulates adult rat behavior, The 40 th Annual Meeting of the Society for Neuroscience (12-17 November 2010, San Diego , CA , U.S.A. ).

16.  Yu-Tien Hsiao, Ning Chiang and Chih-Tien Wang* . SNAP-25 phosphorylation by PKA and PKC differentially regulates fusion pore closure and dilation , The 41 st Annual Meeting of the Society for Neuroscience (11-16 November 2011, Washington , DC , U.S.A. ).

17.  Yu-Chieh Chen, Chung-Wei Chiang, Che-Wei Chang, Chih-Chung Chou, Li-Chung Hsu and Chih-Tien Wang* . Synaptotagmin III confers a unique spatiotemporal expression pattern in the developing rat retina, The 41 st Annual Meeting of the Society for Neuroscience (11-16 November 2011, Washington , DC , U.S.A. ).

18.  Yu-Tien Hsiao, Pin-Chien Huang, Yu-Chieh Chen, Shao-Yen Kao and Chih-Tien Wang* . Presynaptic SNAP-25b regulates the firing size of retinal waves during development, The 42 nd Annual Meeting of the Society for Neuroscience (12-17 October 2012, New Orleans , LA , U.S.A. ).

19.  Ning Chiang, Yu-Tien Hsiao, Pin-Chien Huang and Chih-Tien Wang* . Cysteine string protein- a regulates fusion pore dynamics during Ca 2+ -dependent exocytosis via changing its phosphorylated state , The 42 nd Annual Meeting of the Society for Neuroscience (12-17 October 2012, New Orleans , LA , U.S.A. ).

20.  Shao-Yen Kao, Yu-Chieh Chen and Chih-Tien Wang* . Synaptotagmin III regulates the firing rate of retinal waves in the developing rat retina, The 42 nd Annual Meeting of the Society for Neuroscience (12-17 October 2012, New Orleans , LA , U.S.A. ).

21.  Yung-Chi Chang, Hsin-I Jen, Yu-Tien Hsiao, Yu-Tzu Chang, Yu-Chieh Chen, Juu-Chin Lu and Chih-Tien Wang* . Synergistic actions of synapsin Ia and synaptotagmin IV on oxytocin release from the hypothalamic-neurohypophysial system , The 42 nd Annual Meeting of the Society for Neuroscience (12-17 October 2012, New Orleans , LA , U.S.A. ).

22.  Ching-Feng Chen and Chih-Tien Wang* . Phosphorylation of c ysteine s tring p rotein -α regulates r etinal w aves during development , The 9 th International Symposium on the Kanagawa University-National Taiwan University Exchange Program (13-16 March 2014, Kanagawa , Japan )

23.  Hui-Ju Yang, Yung-Chi Chang and Chih-Tien Wang* . Synapsin Ia, a synaptic vesicle protein, regulates the dynamics of dense-core vesicle exocytosis, The 9 th International Symposium on the Kanagawa University-National Taiwan University Exchange Program (13-16 March 2014, Kanagawa , Japan )

24.  Yu-Tien Hsiao, Cheng-Chang Yang, Yi-Ting Huang and Chih-Tien Wang * . SNAP-25 phosphorylation modulates the exocytotic kinetics in secretory cells and the large-scale network activity in the developing rat retina , The 44 th Annual Meeting of the Society for Neuroscience (15-19 November 2014, Washington , DC , U.S.A. ).

25.  Hui-Ju Yang, Yung-Chi Chang and Chih-Tien Wang* . Synapsin Ia, a synaptic vesicle protein, regulates the dynamics of dense-core vesicle exocytosis, The 44 th Annual Meeting of the Society for Neuroscience (15-19 November 2014, Washington , DC , U.S.A. ).

26.  Cheng-Chang Yang and Chih-Tien Wang* . Synaptotagmin I in RGCs regulates the patterned spontaneous activity in the developing rat retina, The 44 th Annual Meeting of the Society for Neuroscience (15-19 November 2014, Washington , DC , U.S.A. ).

27.  Yi-Ting Huang, Yu-Tien Hsiao, Shao-Yen Kao, Yu-Chieh Chen and Chih-Tien Wang* . Synaptotagmin III modulates the kinetics of regulated exocytosis by Ca 2+ binding to the C2AB domains, The 44 th Annual Meeting of the Society for Neuroscience (15-19 November 2014, Washington , DC , U.S.A. ).

28. Ching-Feng Chen , Yu-Tien Hsiao, Ting-Yu Wo and Chih-Tien Wang* . Phosphorylation of Cysteine String Protein -α Regulates Retinal Waves during Development , The 45 th Annual Meeting of the Society for Neuroscience (17-21 October 2015, Chicago, IL, U.S.A.).

29. Wen-Chi Shu, Yi-Ting Huang, Shao-Yen Kao, Yu-Tien Hsiao and Chih-Tien Wang* . Calcium binding to Synaptotagmin III regulates patterned spontaneous activity during visual circuit development , The 45 th Annual Meeting of the Society for Neuroscience (17-21 October 2015, Chicago, IL, U.S.A.).

30. Hui-Ju Yang and Chih-Tien Wang* . Explore the exocytotic proteins that interact with Synapsin Ia in a phosphorylation-dependent manner , The 46 th Annual Meeting of the Society for Neuroscience (12-16 November 2016, San Diego, CA, U.S.A.).

31.Pin-Chun Chen and Chih-Tien Wang* . The lateral retinohypothalamic tracts surround the vasopressin neurons in the supraoptic nucleus of hypothalamus , The 46 th Annual Meeting of the Society for Neuroscience (12-16 November 2016, San Diego, CA, U.S.A.).

32. Wen-Chi Shu and Chih-Tien Wang* . Synaptotagmin III in developing retinal ganglion cells regulates patterned spontaneous activity and visual circuit development , The 46 th Annual Meeting of the Society for Neuroscience (12-16 November 2016, San Diego, CA, U.S.A.).

33. Ching-Yuan Yang and Chih-Tien Wang* . Stage II retinal waves promote glutamate release in developing rat retinas , The 46 th Annual Meeting of the Society for Neuroscience (12-16 November 2016, San Diego, CA, U.S.A.).

34. Yu-Hung Tsai, Yi-Ting Huang and Chih-Tien Wang* . Calcium binding to Synaptotagmin III regulates the kinetics of fusion pores and the interaction with SNAP-25, The 46 th Annual Meeting of the Society for Neuroscience (12-16 November 2016, San Diego, CA, U.S.A.).

35. Ming-Hsuan Lu and Chih-Tien Wang* . Dysbindin, a schizophrenia susceptibility gene, regulates patterned spontaneous activity in the developing rat retina , The 46 th Annual Meeting of the Society for Neuroscience (12-16 November 2016, San Diego, CA, U.S.A.).

36. Hui-Ju Yang and Chih-Tien Wang* . Investigating the Synapsin Ia's interaction with Syntaxin I in a phosphorylation-dependent manner, The 47 th Annual Meeting of the Society for Neuroscience (11-15 November 2017, Washington, DC, U.S.A.).

37. Pin-Chun Chen and Chih-Tien Wang* . The effects of stage II retinal waves on retinal ganglion cell projection to lateral hypothalamic area, The 47 th Annual Meeting of the Society for Neuroscience (11-15 November 2017, Washington, DC, U.S.A.).

38.Hsin-Yo Chen and Chih-Tien Wang* . A single calcium-binding domain is sufficient to mediate the Syt III's regulation of retinal waves, The 47 th Annual Meeting of the Society for Neuroscience (11-15 November 2017, Washington, DC, U.S.A.).

39. Yi-Wen Lin and Chih-Tien Wang* . The role of ipRGCs in mediating Synaptotagmin I's regulation of retinal waves during development, The 47 th Annual Meeting of the Society for Neuroscience (11-15 November 2017, Washington, DC, U.S.A.).

40. Erh-Chung Chen, Shih-Yuan Liou, Pin-Chun Chen, and Chih-Tien Wang* . Establishment of the cell type-specific gene expression technique to study the regulatory mechanism of oxytocin release, The 47 th Annual Meeting of the Society for Neuroscience (11-15 November 2017, Washington, DC, U.S.A.).


Course Information

LS 1010 General Zoology
B01 16110 The Exploration of Life
MCB 5007 Molecular Cell Biology
MCB 5019 Neural Transmission
MCB 5021 Neural Transmission Seminar
MCB 5026 Current Topics in Molecular Neurobiology Research
MCB 7001 Seminar ( M.S .)
MCB 7002 Research Training (M.S.)
MCB 8002 Research Training (Ph.D.)
Copyright © 2004 Institute of Molecular and Cellular Biology, National Taiwan University

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