Systems Neurobiology Spring School 2006

LECTURE in Japanese

(in alphabetical order)
Speaker Dr. George Augustine (Duke University)
Title Dendritic signal transduction underlying cerebellar long-term synaptic depression
Abstract The goals of this lecture are to: (1) introduce students to caged compounds, light-activated molecules that can be used to examine the temporal and spatial characteristics of chemical signaling; and (2) show how my laboratory has used caged compounds to tease apart the signaling events involved in cerebellar long-term synaptic depression (LTD). LTD is a form of synaptic plasticity that is caused by a reduction in the number of functional AMPA-type glutamate receptors, so that the postsynaptic Purkinje cell is less capable of responding to glutamate released by the presynaptic parallel fibers. A complex network of signal transduction events transduce a brief bout of synaptic activity into a long-lasting change in AMPA receptors. This signal transduction network includes several protein kinases that work in a positive feedback loop that initiates and prolongs the duration of LTD.
Reference Essential:
  1. Finch, E.A., and Augustine, G.J. (1998). Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites. Nature 396, 753-756. [LINK]
  2. Kuroda, S., Schweighofer, N., and Kawato, M. (2001). Exploration of signal transduction pathways in cerebellar long-term depression by kinetic simulation. J. Neurosci. 21, 5693-5702. [LINK]
  3. Miyata, M., Finch, E.A., Khiroug, L., Hashimoto, K., Hayasaka, S., Oda, S.I., Inouye, M., Takagishi, Y., Augustine, G.J., and Kano, M. (2000). Local calcium release in dendritic spines required for long-term synaptic depression. Neuron 28, 233-244. [LINK]
  4. Wang, S.S., Khiroug, L., and Augustine, G.J. (2000). Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate. Proc. Natl. Acad. Sci. USA 97, 8635-8640. [LINK]
Recommended:
  1. Chung, H.J., Steinberg, J.P., Huganir, R.L., and Linden, D.J. (2003). Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression. Science 300, 1751-1755. [LINK]
  2. Doi, T., Kuroda, S., Michikawa, T., and Kawato, M. (2005). Inositol 1,4,5-trisphosphate-dependent Ca2+ threshold dynamics detect spike timing in cerebellar Purkinje cells. J. Neurosci. 25, 950-961. [LINK]
  3. Inoue, T., Kato, K., Kohda, K., and Mikoshiba, K. (1998). Type 1 inositol 1,4,5-trisphosphate receptor is required for induction of long-term depression in cerebellar Purkinje neurons. J. Neurosci. 18, 5366-5373. [LINK]
  4. Kawasaki, H., Fujii, H., Gotoh, Y., Morooka, T., Shimohama, S., Nishida, E., and Hirano, T. (1999). Requirement for mitogen-activated protein kinase in cerebellar long term depression. J. Biol. Chem. 274, 13498-13502. [LINK]
  5. Lev-Ram, V., Makings, L.R., Keitz, P.F., Kao, J.P., and Tsien, R.Y. (1995). Long-term depression in cerebellar Purkinje neurons results from coincidence of nitric oxide and depolarization-induced Ca2+ transients. Neuron 15, 407-415. [LINK]
  6. Linden, D.J. (1996). A protein synthesis-dependent late phase of cerebellar long-term depression. Neuron 17, 483-490. [LINK]
  7. Wang, S.S., Denk, W., and Hausser, M. (2000). Coincidence detection in single dendritic spines mediated by calcium release. Nat. Neurosci. 3, 1266-1273. [LINK]
Optional:
  1. Adams, S.R. and Tsien, R.Y. (1993). Controlling cell chemistry with caged compounds. Annu Rev Physiol. 55:755-784. [LINK]
  2. Augustine, G.J., Santamaria, F., and Tanaka, K. (2003). Local calcium signaling in neurons. Neuron 40, 331-346. [LINK]
  3. Ito, M. (2001). Cerebellar long-term depression: characterization, signal transduction, and functional roles. Physiol. Rev. 81, 1143-1195. [LINK]
Speaker Dr. Michael Hausser (University College London)
Title Dendritic integration in mammalian neurons
Abstract Communication between neurons in the brain occurs primarily through synapses made onto their dendrites. New electrical and optical recording techniques, in conjunction with modelling, have led to tremendous advances in our understanding of how dendrites contribute to neuronal computation in the mammalian brain. The varied morphology and electrical and chemical properties of dendrites enable a spectrum of local and long-range signaling, defining the input-output relationship of neurons and the rules for induction of synaptic plasticity. In my lecture I will describe how the diversity in dendritic signaling allows individual neurons to carry out specialized functions within their respective networks.
Reference Essential:
  1. Hausser, M., Spruston, N. & Stuart, G. (2000). Diversity and dynamics of dendritic signalling. Science 290, 739-744. [LINK]
  2. London, M. & Hausser, M. (2005). Dendritic Computation. Annual Review of Neuroscience 28, 503-532. [LINK]
  3. Magee JC, Johnston D A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science. 1997 Jan 10;275(5297):209-13. [LINK]
  4. Larkum ME, Zhu JJ, Sakmann B (1999). A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398(6725):338-41. [LINK]
Recommended:
  1. Vetter, P., Roth, A. & Hausser, M. (2001). Action potential propagation in dendrites depends on dendritic morphology. Journal of Neurophysiology 85, 926-937. [LINK]
  2. Chadderton, P., Margrie, T.W., & Hausser, M. (2004). Integration of quanta in cerebellar granule cells during sensory processing. Nature 428, 856-860. [LINK]
  3. Hausser M & Mel B (2003). Dendrites: bug or feature? Curr. Opin. Neurobiol. 2003 13(3):372-83. [LINK]
  4. Markram H, Lbke J, Frotscher M, Sakmann B (1997). Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275:213-5. [LINK]
  5. Poirazi P, Brannon T, Mel BW. Pyramidal neuron as two-layer neural network. Neuron. 2003 Mar 27;37(6):989-99. [LINK]
Optional:
  1. Dendrites. Stuart, G., Spruston, N. & Hausser, M. (Eds). Oxford University Press. 1999.
Speaker Dr. Yasunori Hayashi (Massachusetts Institute of Technology)
Title Visualizing molecular mechanisms underlying synaptic plasticity
Abstract So far the synaptic plasticity has been exclusively measured by means of functional read-out: synaptic currents. However, the recent advance in the imaging technology allows us to visualize the biochemical process underlying the synaptic plasticity. This revealed a highly dynamic nature of postsynaptic molecules both under basal and activated status. I will first describe the trafficking of AMPA type glutamate receptor as the underlying mechanism of functional plasticity. Then I will cover the plasticity of the cytoskeletal component, mainly actin, as the underlying mechanism of the structural plasticity of the dendritic spines. I will also describe some preliminary data on the new role of CaMKII as a cytoskeletal component necessary for keeping the spine structure.
Reference
  1. Malinow, R., Mainen, Z.F. & Hayashi, Y. LTP mechanisms: from silence to four-lane traffic. Curr Opin Neurobiol 10, 352-7 (2000). [LINK]
  2. Malinow, R. & Malenka, R.C. AMPA receptor trafficking and synaptic plast icity. Annu Rev Neurosci 25, 103-26 (2002). [LINK]
  3. Hayashi, Y. & Majewska, A.K. Dendritic spine geometry: functional implic ation and regulation. Neuron 46, 529-32 (2005). [LINK]
Speaker Dr. Alex Mogilner (University of California, Davis)
Title Recent quantitative models of protrusion of crawling cells
Abstract Actin-based protrusion is the first step in cell crawling. In the last two decades, the studies of actin networks in the lamellipodium and Listerias comet tail advanced so far that the last goal of the reductionist agenda reconstitution of protrusion from purified components in vitro and in silico became viable. Earlier models dealt with growth of and force generation by a single actin filament. Modern models of tethered ratchet, autocatalytic branching, end-tracking motor action and elastic- and nano- propulsion have recently helped to elucidate dynamics and forces in complex actin networks. I will introduce these models, discuss their limitations and relationships to recent biophysical data and progress being made toward a unified model of protrusion.
Reference Essential:
  1. A. Mogilner, G.Oster, Force generation by actin polymerization II: The elastic ratchet and tethered filaments. Biophysical Journal 84 , 1591-1605 (2003). [LINK]
Additional:
  1. A. Mogilner, G.Oster, Cell motility driven by actin polymerization, Biophysical Journal 71 , 3030-3045 (1996). [LINK]
  2. A. Mogilner, On the Edge: Modeling Protrusion. Cur. Opin. Cell Biol., In Press. [LINK]
  3. A. Mogilner, G. Oster, Polymer Motors: Pushing out the Front and Pulling up the Back. Curr. Biol., 13 , R721-R733 (2003). [LINK]
Speaker Dr. Hitoshi Okamoto (RIKEN Brain Science Institute))
Title Zebrafish as a Model System to Study Neural Circuit Development
Abstract Formation of the neural circuits proceeds in strictly regulated manner. Although study using invertebrate model organisms has lead to discoveries of many important molecules regulating behaviors of growing neurons, it is also desirable to decode the genetically inscribed program for neural circuit formation by directly analyzing the vertebrate model organisms in which both cell biological and genetic manipulations are amenable. I will try to familiarize the participants with zebrafish as a suitable experimental model animal for this study because of its amenability to genetics and various genetic and cellular manipulation by taking our own studies as examples on the hindbrain motor neurons and the asymmetric efferent projection from the habenular nuclei.
Reference Recommended:
  1. Wada H, Iwasaki M, Sato T, Masai I, Nishiwaki Y, Tanaka H, Sato A, Nojima Y, and Okamoto H. (2005) Dual roles of zygotic and maternal Scribble1 in neural migration and convergent extension movements in zebrafish embryos. Development. 132:2273-2285. [LINK]
  2. Uemura, O., Okada, Y., Ando, H., Guedj, M., Higashijima, S., Shimazaki, T., Chino, N., Okano, H., and Okamoto, H. (2005) Comparative functional genomics revealed conservation and diversification of three enhancers of the isl1 gene for motor and sensory neuron-specific expression, Devel. Biol. 278:567-606. [LINK]
  3. Aizawa, H., Bianco, I.H., Hamaoka, T., Miyashita, T., Uemura, O., Concha, M.L., Russell, C., Wilson, S.W., and Okamoto, H., (2005) Laterotopic Representation of Left-Right Information onto the Dorso-Ventral Axis of a Zebrafish Midbrain Target Nucleus, Current Biology, 15: 238-243. [LINK]
  4. Kawakami, A., Nojima, Y., Toyoda, A., Takahoko, M., Satoh, M., Tanaka, H., Wada, H., Masai., I., Terasaki, H., Sakaki, Y., Takeda, H., and Okamoto, H. (2005) The zebrafish-secreted matrix protein You/Scube2 is implicated in long-range regulation of Hdgehog signaling. Current Biology, 15: 480-488. [LINK]
  5. Yamaguchi, M., Tonou-Fujimori, N., Komori, A., Maeda, R., Nojima, Y., Li, H., and Okamoto., H., Masai, I. (2005) Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways, Development. 132:3027-43. [LINK]
Speaker Dr. Hongjun Song (Johns Hopkins University School of Medicine)
Title Molecular mechanisms regulating adult mammalian neurogenesis
Abstract During the last decade, it became well established that neurogenesis, a process of generating functional new neurons from neural stem cells, occurs throughout life in discrete regions of the mammalian central nervous system. Adult neurogenesis recapitulates the process of neuronal development in a mature CNS environment, including proliferation and fate specification of neural progenitors, neuronal maturation, targeting and integration of newborn neurons. In my lecture I will describe the history of the field and general approaches to study adult neurogenesis. I will also discuss recent findings on the molecule mechanisms regulating distinct steps during the adult neurogenesis process.
Reference Essential:
  1. Ming, G.L., and Song. H-j. (2005). Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci. 28, 223-50. [LINK]
  2. Temple, S. (2001). The development of neural stem cells. Nature 414, 112-7. [LINK]
  3. Gage FH. (2000). Mammalian neural stem cells. Science 287, 1433-8. [LINK]
Recommended:
  1. Lie, D.C., Colamarino, S.A., Song, H.J., Desire, L., Mira, H., Consiglio, A., Lein, E.S., Jessberger, S., Lansford, H., Dearie, A.R., Gage, F.H. (2005). Wnt signalling regulates adult hippocampal neurogenesis. Nature 437, 1370-5. [LINK]
  2. Ge, S., Goh, E.L., Sailor, K.A., Kitabatake, Y., Ming, G.L., Song, H. (2006). GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439, 589-93. [LINK]
  3. Zhao, C., Teng, E.M., Summers, R.G. Jr., Ming, G.L., and Gage, F.H. (2006). Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J. Neurosci 26, 3-11. [LINK]
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