Joe Z. Tsien

Joe Z. Tsien, Ph.D., is a brain researcher and geneticist who has pioneered Cre/lox-neurogenetics in mid 1990s, a versatile toolbox for neuroscientists to study the complex relationships between genes, neural circuits, and behaviors. He is also widely known as the creator of smart mouse Doogie in late 1990s while being a faculty at Princeton University. In 2015, he developed the Theory of Connectivity to describe the origin of intelligence: A "Power-of-Two"-based mathematical principle that outlines the basic wiring and computational logic of the brain.

Dr. Tsien is currently the Eminent Scholar in Cognitive and Systems Neurobiology at Georgia Research Alliance, professor of Neurology, and co-Director of the Brain and Behavior Discovery Institute in the Medical College of Georgia at Augusta University in Augusta, Georgia, USA.

Education

Tsien earned his A.B. in Biology/Physiology from East China Normal University in Shanghai (1984) and his Ph.D. in Molecular Biology from the University of Minnesota in 1990. He completed two postdoctoral fellowships with two Nobel laureates, Dr. Eric Kandel at Columbia University and Dr. Susumu Tonegawa at MIT.

Career

In 1997, he became a faculty member in the Department of Molecular Biology at Princeton University, where he created the smart mouse Doogie. He is currently a Georgia Research Alliance Eminent Scholar in Neuroscience. Tsien is currently leading a team of neuroscientists, computer scientists, mathematicians, working on the BRAIN DECODING project initiated in 2007 by Georgia Research Alliance.[1]

Research

Tsien pioneered Cre-loxP-mediated brain subregion- and cell type-specific genetic techniques in 1996,[2] enabling researchers to manipulate or introduce any gene in a specific brain region or a given type of neuron.[3] This transformative technique has led to NIH Blueprint for Neuroscience Research in launching several Cre-driver Mouse Resource projects. Over the past 20 years, Cre-lox recombination-mediated neurogenetics has emerged as one of the most powerful and versatile technology platforms for cell-specific gene knockouts, transgenic overexpression,neural circuit tracing, Brainbow, optogenetics, CLARITY, voltage imaging and chemical genetics.[4][5][6]

Tsien is also widely known as the creator of smart mouse Doogie.[7] While as a faculty at Princeton University, Tsien has speculated that one of the NMDA receptor's subunit may hold the key for superior learning and memory at young ages. Accordingly, his laboratory genetically engineered a transgenic mouse in which they over-expressed the NR2B subunit of the NMDA receptor in the mouse cortex and hippocampus. In 1999, his team reported that the transgenic mouse, nicknamed Doogie, indeed showed to have enhanced synaptic plasticity and enhanced learning and retention as well as greater flexibility in learning new patterns.[8] The discovery of the NR2B as a key genetic factor for memory enhancement prompted other researchers to discover over two dozen other genes for memory enhancement, many of which regulate the NR2B pathway.[9] One of the NR2B-based memory-enhancement strategies, via dietary supplements of a brain-penetrating magnesium ion, magnesium L-threonate, is currently undergoing clinical trials for memory improvement.[10][11]

Tsien has also made several other major discoveries, including the unified cell-assembly mechanism for explaining how episodic memory and semantic memory are generated in the memory circuits,[12][13][14] His laboratory also discovered the nest cells in the mouse brain, revealing how animals recognize the abstract concept of nest or home.[15][16]

Tsien is also the first to show that defective Alzheimer's genes (e.g. presenilin-1) impaired adult neurogenesis in the dentate gyrus of the hippocampus,[17] revealing the role of adult neurogenesis in memory clearance,.[18][19]

In addition, Tsien has developed a method capable of selectively erasing a memory of choice, such as a particular fear memory, in the mouse brain,.[20][21]

Tsien also demonstrated that the NMDA receptor in the dopamine circuit plays a crucial role in the formation of habit,[22][23],.[24]

Tsien is currently leading a team of neuroscientists, computer scientists and mathematicians, who are working on the Brain Decoding Project,[25] a large-scale brain activity mapping effort, which he and his colleagues have initiated since 2007 with the support from the Georgia Research Alliance (GRA).[26]

More recently, Tsien has put forth the Theory of Connectivity to explain the design principle upon which evolution and development may construct the brains to be capable of generating intelligence.[27][28]

Recognition

Tsien has been the recipient of several awards for his research contributions, including

Popular science

Tsien has contributed articles to Scientific American in the areas of neuroscience of memory enhancement and memory decoding [29][30] He wrote chapters on learning and memory in several popular textbooks.

Historiography

According to the Song dynasty book, Tongzhi, the Qian surname (Tsien) descends from one of the legendary Five Emperors (Zhuanxu, mythological emperor of ancient China,Shang dynasty, Chinese: 商朝). Emperor Zhuanxu (Chinese: trad. 顓頊, simp. 颛顼, pinyin Zhuānxū), also known as Gaoyang (t 高陽, s 高阳, p Gāoyáng) who was the grandson of the first Chinese Emperor known as Yellow Emperor, ruled the Yellow River valley, the origin of China, in the second millennium BC from 2514 BC – 2436 BC (Early Bronze Age). During the Five Dynasties and Ten Kingdoms period period (907-960), King Qian Liu and his descendants ruled the independent kingdom of Wuyue in south-eastern China. Joe Tsien was born in 1962 in Wuxi and is the 33rd generation of Qian Liu descendants.

References

  1. ↑ http://gra.org/page/1040/meaning_of_the_mind.html
  2. ↑ Tsien JZ. (2016). Cre-lox neurogenetics: 20 years of versatile applications in brain research and counting...Front. Genet. | doi: 10.3389/fgene.2016.00019. http://journal.frontiersin.org/article/10.3389/fgene.2016.00019/abstract
  3. ↑ Tsien et al. (1996). "Subregion- and cell type-restricted gene knockout in mouse brain". Cell 87: 1317–26. doi:10.1016/S0092-8674(00)81826-7.
  4. ↑ Tsien et al. (1996). "Subregion- and cell type-restricted gene knockout in mouse brain". Cell 87: 1317–26. doi:10.1016/S0092-8674(00)81826-7.
  5. ↑ Taniguchi H, He M, Wu P, Kim S, Paik R, Sugino K, Kvitsiani D, Fu Y, Lu J, Lin Y, Miyoshi G, Shima Y, Fishell G, Nelson SB, Huang ZJ (September 22, 2011). "A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex". Neuron 71 (6): 995–1013. doi:10.1016/j.neuron.2011.07.026. PMID 21943598.
  6. ↑ Cre lines characterized by the JAX Cre Resource
  7. ↑ Wade, Nicholas. "SCIENTIST AT WORK: Joe Z. Tsien; Of Smart Mice and an Even Smarter Man." New York Times, September 7, 1999.
  8. ↑ Tang, YP; Shimizu, E; Dube, GR; Rampon, C; Kerchner, GA; Zhuo, M; Liu, G; Tsien, JZ (Sep 1999). "Genetic enhancement of learning and memory in mice". Nature 401 (6748): 63–9. doi:10.1038/43432. PMID 10485705.
  9. ↑ Lehrer, Jonah (2009). "Neuroscience: Small, furry … and smart". Nature 461 (461): 862–864. doi:10.1038/461862a.
  10. ↑ Cyranoski, David (October 26, 2012). "Testing magnesium's brain-boosting effects Simple ion therapy faces human trials after ten years of preparation". Nature. doi:10.1038/nature.2012.11665. Retrieved November 2014.
  11. ↑ Liu G, Weinger JG, Lu ZL, Xue F, Sadeghpour S. (2015). Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial. J Alzheimers Dis. 2015 Oct 27
  12. ↑ Lin L, Osan R, Shoham S, Jin W, Zuo W, Tsien JZ. Identification of network-level coding units for real-time representation of episodic experiences in the hippocampus.Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6125-30. Epub 2005 Apr 15. http://www.ncbi.nlm.nih.gov/pubmed/15833817
  13. ↑ Lin L, Osan R, Tsien JZ.Organizing principles of real-time memory encoding: neural clique assemblies and universal neural codes. Trends Neurosci. 2006 Jan;29(1):48-57. Epub 2005 Dec 1. Review. http://www.ncbi.nlm.nih.gov/pubmed/16325278
  14. ↑ The Boston Globe: The mouse that remembered Terror of Disney ride sparks brain insight. http://archive.boston.com/yourlife/health/mental/articles/2005/04/12/the_mouse_that_remembered/?page=full
  15. ↑ Lin L, Chen G, Kuang H, Wang D, Tsien JZ. Neural encoding of the concept of nest in the mouse brain.Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6066-71. Epub 2007 Mar 27. http://www.ncbi.nlm.nih.gov/pubmed/17389405
  16. ↑ https://www.newscientist.com/article/dn11460-like-goldilocks-mice-know-a-bed-thats-just-right
  17. ↑ Feng et al., (2001). Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron. Dec 6;32(5):911-26
  18. ↑ News by Nature magazine. http://www.nature.com/news/2001/011207/full/news0111213-2.html
  19. ↑ http://www.alzforum.org/news/research-news/neurogenesis-mechanism-memory-storage-clearance
  20. ↑ Cao, et al., Inducible and selective erasure of memories in the mouse brain via chemical-genetic manipulation.Neuron. 2008 Oct 23;60(2):353-66. doi: 10.1016/j.neuron.2008.08.027. http://www.ncbi.nlm.nih.gov/pubmed/?term=tsien+jz%3B+memory+erasure
  21. ↑ ‘Eternal Sunshine’ drug selectively erases memories by New Scientist. https://www.newscientist.com/article/dn15025-eternal-sunshine-drug-selectively-erases-memories
  22. ↑ Wang et al., NMDA Receptors in Dopaminergic Neurons Are Crucial for Habit Learning. Neuron, Volume 72, Issue 6, p1055–1066, 22 December 2011. http://www.cell.com/neuron/abstract/S0896-6273%2811%2900931-7
  23. ↑ Wall Street Journal: How Habits Hold Us. http://archive.boston.com/yourlife/health/mental/articles/2005/04/12/the_mouse_that_remembered/?page=full
  24. ↑ Video Abstract from NEURON magazine. https://www.youtube.com/watch?v=IVX69AXdYaw
  25. ↑ http://braindecodingproject.org/
  26. ↑ Tsien et al., On Initial Brain Activity Mapping of Episodic and Semantic Memory Code in the Hippocampus. Neurobiology of Learning and Memory, 2013. http://www.sciencedirect.com/science/article/pii/S1074742713001111
  27. ↑ Tsien JZ (2015). A Postulate on the Brain's Basic Wiring Logic.Trends Neurosci. 2015 Nov;38(11):669-71. http://www.sciencedirect.com/science/article/pii/S016622361500209X
  28. ↑ Tsien JZ, (2016) Principles of Intelligence: On Evolutionary Logic of the Brains. Front. Syst. Neurosci. | doi: 10.3389/fnsys.2015.00186, http://journal.frontiersin.org/article/10.3389/fnsys.2015.00186/full
  29. ↑ Tsien, Building a Brainer Mouse. Scientific American, April, p62-68, 2000. http://www.bio.utexas.edu/courses/kalthoff/bio346/PDF/Readings/11Tsien%282000%29brainier.pdf
  30. ↑ Tsien, The memory code, Scientific American, July, 2007; http://redwood.psych.cornell.edu/courses/psych512fall07/papers/Tsien_memorycode_07.pdf

External links

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