Graduate School of Medicine / School of Medicine, Faculty of Medicine

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Developmental & Integrative Neuroscience

Genetic and Behavioral Neuroscience

. Introduction to our research area
Final output of the brain is the behavior, and animal behaviors are defined by the nature (genes) and nurture (environment). The brain mixes these two components to produce the best behavior for the animal under a given environment. In our laboratory, we are interested in the relation between behavior and brain function and use genetic techniques to dissect this relationship. Drosophila melanogaster is the best animal for our purpose. Drosophila has a variety of behaviors, such as courtship, aggression and territorial behaviors, and many behavioral mutants have been established. Furthermore, techniques to study brain functions, optical and electrical, can be readily applied at the neuromuscular synapse. Among basic animal behaviors the “learning” behavior is of our current interest. “Learning” is established by a mixture of nature and nurture. By combining odors and electrical shock, it is possible to “teach” flies. The learned behavior, memory, can be followed quantitatively along the time to estimate the state of memory. There are various mutants that cannot maintain memory, although they can learn at first. That is, they are forgetful. By studying these mutants we can elucidate the cellular and molecular mechanism of memory maintenance. In Drosophila, all genomes are already known, which provides us a powerful tool to study the relation between behaviors and genes.

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  • Clinical Activities
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Professor Yuchio Yanagawa, Ph.D., M.D.  
Associate Professor Yasuhiko Saito, Ph.D.  
Research Associates Toshikazu Kakizaki, Ph.D.  
  Hideki Miwa, Ph.D.  

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Research & Education

Research content

Current research topics
We are currently studying following specific topics using Drosophila.
i) Basic synaptic functions; the synapse is the functional element for the brain functions. In Drosophila, there are mutants that have various defects in the synaptic function. We use optical and electrical techniques to define the defects in those mutants in order to elucidate molecular mechanisms underlying synaptic transmission.
ii) Molecular mechanism of long-term memory; Drosophila has unique courtship behaviors, which is modified by past experience. This modified behavior is maintained for a prolong time (5 to 7 days). This is one type of long-term memory. We study how this long-term memory is affected by various mutations.
iii) Molecular mechanism of taste perception; flies can distinguish a variety of tastes and select foods. We are cloning receptors for “sweet” and “sour” tastes and studying their pathways within the brain using molecular biological techniques.

Business education

We are teaching students in 2nd and 3rd grades with following lectures and laboratory courses.
i) Neurophysiology; “Excitation-contraction coupling in muscles”, “Higher functions of cerebral cortex” for 2nd grade students
ii) Behavioral science; “Behavior and heredity” for 3rd grade students
Laboratory courses;
i) “Ionic mechanisms of nerve action potential” for 2nd grade students
ii) Elective basic medical research course for 3rd grade students;
“The effect of nicotine on Drosophila behaviors” by H. Kuromi
“Assessment of long-term memory using Drosophila male courtship behaviors” by T. Sakai.
“Measurement of taste discrimination in Drosophila” by K. Ueno.

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Clinical Activities

(no clinical assignments)

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Citizenship Activities

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  • Shino M, Kaneko R, Yanagawa Y, Kawaguchi Y, Saito Y. Electrophysiological characteristics of inhibitory neurons of the prepositus hypoglossi nucleus as analyzed in Venus-expressing transgenic rats. Neuroscience 197, 89-98, 2011
  • Augustinaite S, Yanagawa Y, Heggelund P. Cortical feedback regulation of input to visual cortex: role of intrageniculate interneurons. J Physiol. 589, 2963-77, 2011
  • Saito K, Kakizaki T, Hayashi R, Nishimaru H, Furukawa T, Nakazato Y, Takamori S, Ebihara S, Uematsu M, Mishina M, Miyazaki JI, Yokoyama M, Konishi S, Inoue K, Fukuda A, Fukumoto M, Nakamura K, Obata K, Yanagawa Y. The physiological roles of vesicular GABA transporter during embryonic development: a study using knockout mice. Molecular Brain 3:40, 2010
  • Saito Y, Yanagawa Y. Synaptic mechanism for the sustained activation of oculomotor integrator circuits in the rat prepositus hypoglossi nucleus: Contribution of Ca2+-permeable AMPA receptors. J Neurosci. 30, 15735-15746, 2010.
  • Polepalli JS, Sullivan RKP, Yanagawa Y, Sah P. A specific class of interneuron mediates inhibitory plasticity in the lateral amygdala. J Neurosci. 30, 14619-14629, 2010.
  • Muguruma K, Nishiyama A, Ono Y, Miyawaki H, Mizuhara E, Hori S, Kakizuka A, Obata K, Yanagawa Y, Hirano T, Sasai Y. Ontogeny–recapitulating generation and tissue integration of ES cell–derived Purkinje cells. Nature Neurosci. 13, 1371-1380, 2010.
  • Wang Y, Kakizaki T, Sakagami H, Saito K, Ebihara S, Kato M, Hirabayashi M, Saito Y, Furuya N, Yanagawa Y. Fluorescent labeling of both GABAergic and glycinergic neurons in vesicular GABA transporter (VGAT)-Venus transgenic mouse. Neuroscience 164, 1031-1043, 2009.
  • Niquille M, Garel S, Mann F, Hornung JP, Otsmane B, Chevalley S, Parras C, Guillemot F, Gaspar P, Yanagawa Y, Lebrand C. Transient Neuronal Populations Are Required to Guide Callosal Axons: A Role for Semaphorin 3C. PLoS Biol 7, e1000230, 2009.
  • Akashi K, Kakizaki T, Kamiya H, Fukaya M, Yamasaki M, Abe M, Natsume R, Watanabe M, Sakimura K. NMDA receptor GluN2B (GluR epsilon 2/NR2B) subunit is crucial for channel function, postsynaptic macromolecular organization, and actin cytoskeleton at hippocampal CA3 synapses. J Neurosci 29, 10869-82, 2009.
  • Pan BX, Dong Y, Ito W, Yanagawa Y, Shigemoto R, Morozov, A. Selective gating of glutamatergic inputs to excitatory neurons of amygdala by presynaptic GABAb receptor. Neuron 61, 917-929, 2009.
  • Bi W, Sapir T, Shchelochkov OA, Zhang F, Withers MA, Hunter JV, Levy T, Shinder V, Peiffer DA, Gunderson KL, Nezarati MM, Shotts VA, Amato SS, Savage SK, Harris DJ, Day-Salvatore DL, Horner M, Lu XY, Sahoo T, Yanagawa Y, Beaudet AL, Cheung SW, Martinez S, Lupski JR, Reiner O. Increased LIS1 expression affects human and mouse brain development. Nature Genet 41, 168-177, 2009.
  • Kaneko K, Tamamaki N, Owada H, Kakizaki T, Kume N, Totsuka M, Yamamoto T, Yawo H, Yagi T, Obata K, Yanagawa Y. Noradrenergic excitation of a subpopulation of GABAergic cells in the basolateral amygdala via both activation of nonselective cationic conductance and suppression of resting K+ conductance: A study using glutamate decarboxylase 67-green fluorescent protein knock-in mice. Neuroscience 157, 781-797, 2008.
  • Ikeda K, Yanagawa Y, Bekkers J. Distinctive quantal properties of neurotransmission at excitatory and inhibitory autapses revealed using variance-mean analysis. J. Neurosci 28, 13563-13573, 2008.
  • Gandhi SP, Yanagawa Y, Stryker MP. Delayed plasticity of inhibitory neurons in developing visual cortex. Proc Nat Acad Sci USA 105: 16797-16802, 2008.
  • Obata K, Hirono M, Kume N, Kawaguchi Y, Itohara S, Yanagawa, Y. GABA and synaptic inhibition of mouse cerebellum lacking glutamate decarboxylase 67. Biochem Biophys Res Commun 370, 429-433, 2008.
  • Uematsu M, Hirai Y, Karube F, Ebihara S, Kato M, Abe K, Obata K, Yoshida S, Hirabayashi M, Yanagawa Y, Kawaguchi Y. Quantitative chemical composition of cortical GABAergic neurons revealed in transgenic Venus-expressing rats. Cereb Cortex 18, 315-330, 2008.
  • Saito Y, Takazawa T, Ozawa S: Relationship between afterhyperpolarization profiles and the regularity of spontaneous firings in rat medial vestibular nucleus neurons. Eur J Neurosci 28:288-298, 2008.
  • Miwa H, Fukaya M, Watabe AM, Watanabe M, Manabe T: Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and long-term potentiation in the adult mouse CNS. J Physiol 586:2539-2550, 2008.
  • Labouebe G, Lomazzi M, Cruz HG, Creton C, Lujan R, Li M, Yanagawa Y, Obata K, Watanabe M, Wickman K, Boyer SB, Slesinger PA, Luscher C. RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nature Neurosci 10, 1559-1568, 2007.
  • Berghuis P, Rajnicek AM, Morozov YM, Ross RA, Mulder J, Urban GM, Monory K, Marsicano G, Matteoli M, Canty A, Irving AJ, Katona I, Yanagawa Y, Rakic P, Lutz B, Mackie K, Harkany T. Hardwiring the brain: Endocannabinoids shape neuronal connectivity. Science 316, 1212-1216, 2007
  • Shimizu H, Watanabe E, Hiyama T, Nagakura A, Fujikawa A, Okado H, Yanagawa Y, Obata K, Noda M. Glial Nax channels control lactate signaling to neurons for brain [Na+] sensing. Neuron 54, 59-72, 2007.
  • Marowsky A, Yanagawa Y, Obata K, Vogt KE. A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function. Neuron 48, 1025-1037, 2005

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Historical background
Before reformation in 2003, the Section of Genetics, Development and Behaviors was the Section of Physiology in the Institute of Behavioral Sciences. The Institute was founded on April 1, 1965 and the Section of Physiology was installed in the same year. The first chairman of the Section was Professor Takehisa Hirao, who studied the ethology of individual mouse and group of mice. In 1992, Yoshiaki Kidokoro succeeded the professorship and has started studies on the relation between brain function and behavior using Drosophila. Currently our group is composed of investigators with different backgrounds, who are taking multidisciplinary approaches to the ultimate goal of understanding the relation between genetics and behaviors.