- Department：
- Position：Director, Senior Investigator
- Research Field：Activity-dependent plasticity of neural circuits, Synaptic structural mechanisms underlying memory storage, Neural circuit basis of higher cognitive functions in primates
- Phone：
- E-mail：muming.poo@icpbr.ac.cn
Mu-Ming Poo - together with Nikos K. Logothetis - is Co-Director of the International Center for Primate Brain Research (ICPBR) in Shanghai, China. He is also the Scientific Director of Institute of Neuroscience (ION) of Chinese Academy of Sciences (CAS) and CAS Center for Excellence for Brain Science & Intelligence Technology (CEBSIT). He also serves as Director of Shanghai Center for Brain Science and Brain-Inspired Technology, and Emeritus Paul Licht Distinguished Professor in Biology at University of California, Berkeley. During 1976-2012, he had served on the faculty of UC Irvine, Yale, Columbia, UCSD, and UC Berkeley. He was the founding director of ION during 1999-2019.
Poo received B.S. in physics in 1970 from Tsinghua University (Taiwan), and Ph.D. in biophysics in 1974 from Johns Hopkins University, where he developed the photobleaching method for quantitative measurement of protein mobility in the cell. He used the method to achieve the first measurement of the lateral diffusion coefficient of a membrane protein in cell membrane (i.e., rhodopin diffusion in cytoplasmic disc membrane of rod photoreceptors), a value later became the bench mark for free lateral diffusion of an integral membrane protein in situ. During his postdoctoral work at Purdue University (1974-1976), he became interested in neural development and studied the galvanotropic response of growing neurites, and discovered the phenomenon of in situ electrophoretic movement of membrane proteins in the plasma membrane, suggesting a potential mechanism for the effect of extracellular electric field on cellular functions. After establishing his own laboratory in 1976, his research interests spread to many subjects in molecular and cellular neurobiology. For examples, the mobility and localization of nicotinic receptors in the postsynaptic muscle membrane during neuromuscular synaptogenesis; transmitter secretion from the neurite growth cone before and after synaptogenesis; cytoplasmic mechanisms determining the turning response of growth cones towards extracellular nerve guidance factors, and those underlying the development and maintenance of polarized growth of the axon and dendrites; activity-dependent synaptic competition at developing neuromuscular junctions and retinotectal synapses; the critical role of relative timing of pre- and postsynaptic spiking in regulating synaptic efficacy, the function of neurotrophins as modulators of synaptic efficacy; long-range retrograde and collateral propagation of long-term potential (LTP) and long-term depression (LTD) in the presynaptic neuron; the precise time window for the pre- and postsynaptic spiking activity to generate LTP and LTD both in vitro and in vivo; the role of spike timing-dependent plasticity (STDP) in developing direction-sensitive visual neurons and in learning motor sequences; dendritic spine dynamics associated with long-term depression and long-term fear memory formation.
During the decade of 2009-2019, Poo also built a non-human primate (NHP) research team at ION from scratch, and had recruited more than ten lab heads specialized in various areas of HNP research (reproductive biology, genome analysis and editing, systems neurophysiologists, and brain imaging). The establishment of ICPBR brought in five more labs in 2021. He also established in ION a large non-human primate (NHP) facility of international standards for both macaque monkeys and marmosets. He himself was involved in several NHP projects using the facility. These included the induction of mirror self-recognition in rhesus monkeys by associative training for perceiving coincident visual formation (mirror images) with somatosensory/proprioceptive information (self-awareness); syllable-specific neuronal responses in the marmoset primary auditory cortex; cloning of macaque monkeys by somatic cell nuclear transfer (SCNT); development of psychosis macaque models by genetic deletion of circadian rhythm core gene BMAL1 and SCNT cloning of a BMAL1-deleted monkey exhibiting psychosis-like phenotypes.
Poo had served on the Scientific Advisory Board for many institutions, including Developmental Neuroscience Panel of USNSF, Cell Biology and Physiology Study Section of NIH, Hong Kong University of Science and Technology Preparatory Committee, Long-term Fellowship Review Board, Human Frontier Science Program, Brain Research Center of University System of Taiwan, Institutes of Molecular Biology, Biomedical Sciences, Biochemistry, Linguistics of Academia Sinica in Taiwan, Brain Science Institute of RIKEN, Japan, IBRO Neuroscience School Board, University Advisory Council of National Yang Ming-Jiao Tong University and National Tsinghua University (Taiwan); Peter Gruber Foundation Neuroscience Prize Selection Committee, Friedrich Miescher Institute of Basel, National Center for Biological Sciences of Bangalore, Ralph Gerald Neuroscience Award Committee, Pfizer Biotherapeutics & Bioinnovation Center, Grand Challenges in Global Mental Health of NIMH; IBRO Congress Program Committee; HHMI Investigator Review Committee, HHMI Collaborative Innovation Award Program Committee, National Institute of Neuroscience of Korea, Korean Institute of Science and Technology, Queensland Brain Institute; Neurospin Brain Imaging Center of France, Lundburg Foundation Brain Prize Committee, State Key Laboratory of Brain Cognition of Hong Kong University, IBRO External Review Committee, Center of of Excellence for Molecular and Cellular Neuroscience at Hong Kong University of Science & Technology, IDG/McGovern Institute of Tsinghua University, Beijing Center for Brain Science and Brain-Inspired Technology.
Poo had served on the editorial board for Journal of Cell Biology, Neuron, Journal of Neuroscience, Journal of Biomedical Sciences, NeuroSignals, Developmental Neurobiology, Network, Progress in Neurobiology, Experimental Neurology, Neural Development, Journal of Physiology, Journal of Neuroscience Research, Journal of Biology, BMC Biology, Neuroscience Bulletin; Faculty 1000 International Scientific Advisory Board. He had also served as an Editor of Biochemical and Biophysical Research Communications and Developmental Neurobiology, a guest Editor of Current Opinions in Neurobiology, and Executive Editor-in-Chief of National Science Review.
Honors and Prizes
2020 EDAB Lecture on Neuroethics, Federation of European Neuroscience Societies Forum
2019 Dean’s Lecture in Sciences, Radcliffe Institute, Harvard University
2019 Docteur Honoris Causa, Claude Bernard University of Lyon, France
2018 Inaugural Sherrington Lecture, Oxford University
2018 20th Stephen Kuffler Lectures, University of California at San Diego
2016 Distinguished Visiting Fellow, Institute of Advanced Studies, HKUST
2014 Docteur Honoris Causa, Hong Kong University of Science and Technology
2014 Founding Member, Hong Kong Academy of Science
2013 Wals Lecture, National Institutes of Health
2013 Grass Lecture, Marine Biological Laboratory
2012 Hertie Lecture, Forum of European Neuroscience Society Annual Meeting
2011 Presidential Lecture, Society for Neuroscience, Washington DC.
2011 Member, Chinese Academy of Sciences
2010 Merson Lecture, Queensland Brain Institute
2010 Qiu-shi Distinguished Scientist Award, Hong Kong
2009 Special Lecture, International Union of Physiological Sciences
2009 Member, US National Academy of Sciences
2009 Numa Memorial Lecture, Kyoto University
2008 Killam Lecture, Montreal Neurological Institute/McGill University
2005 P.R.China International Science & Technology Cooperation Award
2005 Heller Lecture in Computational Neurobiology, Hebrew University
2004 Teuber Lecture, MIT
2003 Docteur Honoris Causa, Ecole Normale Supérieure, Paris
2003 University Lecture, Rockefeller University
2002 Ameritec Prize for Paralysis Research
2001 Fellow, American Association for Advancement of Science
2000 Academician, Academia Sinica. Taiwan
1998 Javitz Neuroscience Investigator Award of NIH
1. Activity-dependent plasticity of neural circuits
Activity-induced changes in the structure and function of synaptic connections are responsible for experience-dependent development and refinement of neural circuits, as well as learning and memory functions of the brain. Correlated spiking of pre- and postsynaptic neurons is capable of inducing persistent changes in synaptic efficacy, known as long-term potentiation (LTP) and long-term depression (LTD). Moreover, the temporal order of pre- and postsynaptic spiking is critical in determining whether LTP and LTD will be induced at the synapse. This spike timing-dependent plasticity (STDP) may provide a mechanism for the neural circuit to store temporal sequence information.? We are testing the hypothesis that neuronal ensembles in the brain use STDP to store learned sequence of sensory and motor information, and retrieval of stored sequence information could be accomplished by partial activation of a subset of neuronal assembles. We are using multi-electrode array recording, calcium imaging over large populations of neurons over prolonged periods, and optogenetic manipulation of selective neuronal populations in vivo to test this hypothesis.?
2. Synaptic structural mechanisms underlying memory storage
Activity-induced modifications associated with LTP and LTD are known to be accompanied by structural changes at synapses that may serve for long-term storage of memory. While large-scale formation and elimination of new synapses have been observed during early brain development, after injury of adult brain, and in cultures of brain slices and dissociated neurons, the extent of structural rewiring during physiological memory formation and after injury of the adult brain remains unclear. Using long-term two-photon imaging at specific synaptic connections that may be involved in long-term memory, we are searching for the structural changes of synaptic connections that are causally related to the formation and consolidation of long-term memory in the cortical and subcortical structures，as well as the changes in the dynamics of activity-induced synaptic changes associated with aging and brain disorders.
3. Neural circuit basis of higher cognitive functions in primates
Substantial progress has been made in our understanding of neural substrates underlying basic cognitive functions, e.g., sensory perception, multi-sensory integration, learning and memory, decision-making, and attention, using a variety of model organisms.? By contrast, we knew very little about higher cognitive functions that are rather unique in humans, including complex executive functions, empathy, cooperative social behaviors, self-awareness, and language. It is generally agreed that evolutionary changes in the genetic program of humans must account for the emergence of cognitive functions that are uniquely human.? One approach to understanding their neural substrates is to introduce human-specific genes into non-human primates and dissect the corresponding changes in the development of neural circuits and associated cognitive behaviors of these genetically modified non-human primates. With the recent development of efficient methods of genetic manipulation in macaque monkeys and marmosets, this approach is now within the horizon of neurobiological research. In collaboration with other laboratories, we are also taking the initial steps in studying primate-specific cognitive functions, such as self-awareness and complex vocal communication.
1. Poo, M-m., R.A. Cone. Lateral diffusion of rhodopsin in the photoreceptor membrane. Nature 247:438-441 (1974).
2. Orida, N.K. Poo M-m. Electrophoretic movement and localization of acetylcholine receptors in the embryonic muscle cell membrane. Nature 275: 31-35 (1978).
3. Poo, M-m. Rapid lateral diffusion of functional acetylcholine receptors in embryonic muscle membrane. Nature 295:332-334 (1982).
4. Young, S.H. and M-m. Poo. Spontaneous release of transmitter from growth cone of embryonic neuron. Nature 305:634-637 (1983).
5. Lo, Y. and Poo, M-m. Activity-dependent synaptic competition in vitro: Heterosynaptic suppression of developing synapses. Science 254:1019-1022 (1991).
6. Dan, Y. and Poo, M. Hebbian depression of isolated neuromuscular synapses in vitro. Science 256: 1570-1573 (1992).
7. Alder, J., Lu, B., Valtorta, F., Greengard, P., and Poo, M-m. (1992) Transmitter secretion reconstituted in Xenopus oocytes: Requirement for synaptophysin. Science 257: 657-661.
8. Dan, Y. and Poo, M-m. (1992) Quantal transmitter secretion from myocytes loaded with acetylcholine. Nature 359: 733-737.
9. Popov, S. Brown, A. and Poo, M-m. Forward plasma membrane flow in growing nerve processes. Science 259: 244-246 (1993).
10. Lohof, A., Ip, N. and Poo, M-m. Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363: 350-353 (1993).
11. Zheng, J., Felder, M., Connor, J., and Poo, M-m. Turning of nerve growth cones induced by neurotransmitters. Nature 368: 140-144 (1994).
12. Stoop, R., and Poo, M-m. Potentiation of transmitter release by ciliary neurotrophic factor requires somatic signaling. Science 267: 695-699 (1995)
13. Song, H-j. Ming, G-l., and Poo M-m. A cAMP-induced switching of turning direction of nerve growth cones. Nature 388: 275-279 (1997).
14. Fitzsimonds, R., Song, H-j. and Poo, M-m. Propagation of activity-dependent synaptic depression in small neural networks. Nature 388: 439-448 (1997).
15. Zhang, L., Tao, H-z., Holt, C., Harris, W., and Poo, M-m. A critical window in the cooperation and competition among developing retinotectal synapses. Nature 395: 37-44 (1998).
16. Song, H-j., Ming, G-l., He, Z, Lehmann, M., McKerracher, L., Tessier-Lagvine, M., and Poo, M-m. Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 281: 1515-1518 (1998).
17. Bi, Q. and Poo, M-m. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J. Neurosci. 18: 10464-10472 (1998).
18. Boulanger, L. and Poo, M-m. Gating of BDNF-induced synaptic potentiation by cAMP. Science 284:1982-1984 (1999).
19. Bi, G. and Poo, M-m. Distributed synaptic modification in neural networks induced by patterned stimulation. Nature 401: 792-796 (1999).
20. Hong, K., Nishiyama, M., Henley, J., Tessier-Lavigne, M., and Poo, M-m. Calcium signaling in the guidance of nerve growth by netrin-1. Nature 403: 93-98 (2000).
21. Nishiyama, M., Hong, K., Mikoshiba, K., Poo, M-m. and Kato, K. Release of internal Ca2+ regulates the polarity and input specificity of synaptic modification. Nature 408: 584-588 (2000).
22. Ganguly, K., Schinder, A., Wong, S. and Poo, M-m. GABA itself promotes the developmental switch of neuronal GABAergic transmission from excitation to inhibition. Cell 105: 521-532 (2001)
23. Ming, G., Wong, S., Henley, J., Yuan, X., Song, H., Spitzer, N., and M-m. Poo. Adaptation in the chemotactic guidance of nerve growth cones. Nature 417, 411-8 (2002)
24. Engart, F., Tao, H., Zhang, L., and M-m. Poo. Moving stimuli induces direction-sensitive responses of developing tectal neurons. Nature 419, 470-474 (2002)
25. Zhou, Q., Tao, H., and M-m. Poo. Reversal and stabilization of synaptic modifications in a developing visual system. Science 300, 1953-7 (2003)
26. Li, C.Y., Liu, J.T., Duan, S.M. & Poo, M-m. Bi-directional modulation of presynaptic neuronal excitability induced by correlated pre- and postsynaptic activity. Neuron 41:257-68 (2004)
27. Du, J-l. & Poo, M-m. Rapid BDNF-induced retrograde synaptic modification in a developing retinotectal system. Nature 429: 878-83 (2004)
28. Zhou, Q., Homma, K.J., & Poo, M-m. Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses Neuron 44: 749-57 (2004)
29. Wang, G.X. & Poo, M-m. Requirement of TRPC channels in netrin-1-induced chemotropic turning of nerve growth cones. Nature 454: 898-904 (2005)
30. Liu, Q-s., Pu, L. & Poo, M-m. Repeated cocaine exposure facilitates LTP induction in midbrain dopamine neurons. Nature 437:1027-31 (2005)
31. Guan, C-b, Xu, H-t., Yuan, X-b. & Poo, M-m. Long-range Ca2+ signaling mediates reversal of neuronal migration induced by Slit-2. Cell l29: 385-395 (2007)
32. Shelly, M., Cancedda, L., Sumbre, G. & Poo, M-m. LKB1/STRAD promotes axon initiation during neuronal polarization. Cell 129: 565-77 (2007)
33. Sumbre, G., Muto, A., Baier H., Poo M-m. Entrained rhythmic activities of neuronal ensembles as perceptual memory of time interval. Nature 456:102-6 (2008)
34. Song A.H., Wang D., Chen G., Li Y., Luo J., Duan S, & Poo M-m. A selective filter for cytoplasmic transport at the axon initial segment. Cell 136: 1148-60 (2009)
35. Shelly M., Lim B.K., Cancedda L., Heilshorn S.C., Gao H., Poo M-m. Local and long-range reciprocal regulation of cAMP and cGMP in axon/dendrite formation. Science 327: 547-52 (2010).
36. Xu S, Jiang W, Poo M-m, Dan Y. Activity recall in a visual cortical ensemble. Nat Neurosci. 15:449-55 (2012)
37. Yang Y, Liu D-q, Sun Y-g, Zuo Y, Poo M-m. Remodeling of amygadala-auditory cortex synapses associated with auditory fear learning. Nat. Neurosci. 19:1348-55 (2016)
38. Chang L, Zhang S, Poo MM, Gong N. Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images. Proc. Natl. Acad. Sci. USA. 114:3258-3263 (2017)
39. Liu Z, Cai YJ, Yan W. Nie YH, Zhang CC, Xu YT, Zhang XT, Lu Y, Wang ZY, Poo, MM, Sun Q. Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer, Cell 172:881-887 (2018)
40. Zeng HH, Huang JF, Li JR, Shen ZM, Gong N, Wen YQ, Wang LP and Poo MM. Distinct neuron populations for simple and compound calls in the primary auditory cortex of awake marmosets. Nat. Sci. Rev. 8: nwab126, 2021, https://doi.org/10.1093/nsr/nwab126 (2021)
Ten Selected Review Articles:
1. Poo, M-m. In situ electrophoresis of membrane components. Ann. Rev. Biophys. Bioeng. 10:245-276 (1981).
2. Poo, M-m. Mobility and localization of proteins in excitable membranes. Ann. Rev. Neurosci. 8:368-406 (1985).
3. Fitzsimonds, R. and M-m. Poo (1998) Retrograde signaling in the development and modification of synapses. Physiol. Rev. 78: 143-170.
4. Poo, M-m. Neurotrophins as synaptic modulators. Nat. Rev. Neurosci. 2: 24-32 (2001).
5. Bi, G. and Poo, M-m. Synaptic modification by correlated activity: Hebb’s postulate revisited. Annu. Rev. Neurosci. 24: 139-66 (2001)
6. Dan, Y. & Poo, M-m. Spike timing-dependent plasticity: from synapse to perception. Physiol. Rev. 86:1033-48 (2006).
7. Cheng PL and Poo M-m. Early events in axon/dendrite polarization. Annu Rev Neurosci. 35:181-201 (2012)
8. Park H, Poo M-m.Neurotrophin regulation of neural circuit development and function. Nat. Rev. Neurosci. 14:7-23 (2013)
9. Ganguly, K., Poo, M-m. Activity-dependent neural plasticity from bench to bedside. Neuron 30:729-41 (2013)
10. Poo, M. Transcriptome, connectome and neuromodulation of the primate brain. Cell l85: 2636-2639 (2022)