Connecting synaptic plasticity to memory using Drosophila feeding circuit and Drosophila embryonic neuromuscular junction.
My lab is trying to ask a fundamental question gHow do we remember?h by studying synaptic physiology in the fruit fly, Drosophila. I believe that memory is stored as a series of neurons connected through strengthened synapses, in which sequential firing of the neurons allows recall of specific events (Fig. 1). Therefore, understanding mechanisms of synaptic modification is a key to understanding mechanisms underlying memory. Taking advantage of a combination of synaptic physiological methods on highly plastic Drosophila embryonic neuromuscular synapses (neuromuscular junction, NMJ) and sophisticated Drosophila genetics, we have proposed a novel hypothesis, glocal feedback modelh as a potential molecular and cellular basis of memory formation (Yoshihara et al., 2005, Science 310: 858-863; Fig. 2). In this model, I postulate that mutual intensification between presynaptic and postsynaptic cells by a positive feedback loop at single synapses keeps individual synapses potentiated, leading to eventual morphological change and perpetually strengthened synapses, storing memory. In my lab, we are testing this working hypothesis to answer the question ghow do we remember?h, by a novel approach using a pair of feeding command neurons, Feeding neuron (Fdg neuron; Fig. 3). We have performed behavioral screening on NP lines (Yoshihara and Ito, 2000, Drosoph. Inf. Serv., 83, 199-202) to establish a new system to connect synaptic plasticity to memory, and finally identified the Fdg neuron (Flood, Iguchi et al., 2013, Nature, 499: 83-87), which is ideal for neurophysiological analysis of classical conditioning demonstrated by Ivan Pavlov (Fig. 4) to connect synaptic plasticity to memory mechanism. We are now establishing novel protocols of Pavlovian conditioning to gwitnessh memory formation as real-time synaptic change in an experimental system I have devised for simultaneous observation of the brain and behavior of a single fruit fly (Yoshihara, 2012, JoVE; 62, 3625; Fig. 5). Through these novel approaches using Drosophila allowing us to perform comprehensive genetic analyses, we are trying to understand basic principle on molecular and cellular mechanism of memory formation.
We are continuing detailed analysis on synaptic plasticity of neuromuscular synapses as a simple cellular model for comparison with central synapses in the brain (this study was supported by NIH R01 grant of U.S.A.). In addition to the plasticity projects, we are also studying basic mechanism of synaptic transmission, which is not fully understood yet. For these synaptic transmission projects, we are taking advantage of Drosophila embryonic neuromuscular synapses, which is suitable for quantitative synaptic physiology even in lethal mutants, as shown in our previous works on function of synaptic molecules (Yoshihara et al., 1999, J. Neurosci. 19: 2432-2441; Yoshihara et al., 2000, J. Neurosci. 20: 8315-8322; Yoshihara and Littleton, 2002 Neuron, 36, 897-908; Yoshihara et al., 2010, Proc. Natl. Acad. Sci. USA, 107, 14869-14874). We are collaborating with the lab of Prof. J. Troy Littleton at MIT for these neuromuscular projects.
We greatly thank for generous support to Moto lab by Dr. Iwao Hosako, the Director General of the Advanced ICT Research Institute, Dr. Kazuhiro Oiwa, the Distinguished Researcher of the National Institute of Information and Communications Technology, and Dr, Hiroaki Kojima, the Director of Bio ICT Laboratory.
Drosophila Synaptic plasticity/memory team
Flood, T., Gorczyca, M., White, B., Ito, K. and Yoshihara, M.* A large-scale behavioral screen to identify neurons controlling motor programs in the Drosophila brain.
Flood, T., Iguchi, S. , Gorczyca, M. , White, B., Ito, K. and Yoshihara, M. *
Korkut, C, Li, Y, Koles, K, Brewer, C, Ashley, J, Yoshihara, M, Budnik, V.
Yoshihara, M., * Guan, Z. and Littleton , J.T.
Yoshihara, M., * Adolfsen, B., Galle, K.T. and Littleton, J.T.
Adolfsen, B., Saraswati, S., Yoshihara, M. and Littleton, J.T.
Lee, W.C., Yoshihara, M. and Littleton, J.T.
Reickhof, G.E., Yoshihara, M., Guan, Z. and Littleton, J.T.
Yoshihara, M. * and Littleton, J.T.
Hayashi, S., Ito, K. Sado, Y.,
Taniguchi, M., Akimoto, A., Takeuchi, H., Aigaki, T., Matsuzaki, F., Nakagoshi,
H., Tanimura, T., Ueda, R., Uemura, T., Yoshihara, M. and Goto. S. (2002) GETDB, a database compiling expression patterns and molecular locations
of a collection of Gal4 enhancer traps. Genesis
Takasu-Ishikawa, E.*, Yoshihara, M.*, Ueda, A., Rheuben, M. B., Hotta, Y. and Kidokoro, Y.
Yoshihara, M., Suzuki, K. and Kidokoro, Y.
Yoshihara, M., and Ito, K.
Yoshihara, M., Ueda, A., Zhang, D., Deicher, D. L., Schwarz, T.L. and Kidokoro, Y.
Yoshihara, M., Rheuben, M. B. and Kidokoro, Y.
Review in English
Yoshihara M. *, Ito K.
Yoshihara, M. * and Montana, E.S.
Yoshihara, M., Adolfsen, B. and Littleton, J.T.
Yoshihara, M., Ensminger , A. and Littleton, J. T.
Review in Japanese
gTo eat or not to eat. That is the questionh: VEWEoGÛHs®ÌR}hj
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We are trying to undersand basic principle of memory formation by connecting synaptic plasticity to memory at this Feeding (Fdg) neuron.
Moto lab moved from@U.S, and@restarted at Motofs home town, Kobe, Japan,
in the spring of 2014 in the bio ICT laboratory of the National Institute
of Information and Communications technology ("NICT Kobe").
In June, 2014, Nakajima-san started fly food cooking!
Moto taught as an instructor (a 3-hour lecture in the morning and a lab course in the whole afternoon) in the Cold Spring Harbor Course, Neurobiology of Drosophila in July (http://meetings.cshl.edu/
Moto gave a plenary lecture at International Congress of Neuroethology on July 31st, 2014.
Akira, who had been working in the US Moto lab, rejoined the lab at Kobe on August 1st, 2014 as a researcher to continue the memory project.
Moto gave a plenary lecture at Synapse Workshop at National Institute for Physiological Sciences on December 2nd, 2014.
Akira made a poster presentation at Synapse Workshop at National Institute for Physiological Sciences on December 2nd, 2014.
Moto gave a talk for 1048th Life Science Seminar at University of Tokyo on July 10th, 2015.
Akira made a poster presentation at the 38th Annual Meeting of the Japan Neuroscience Society on July 29th, 2015.
Akira made a poster presentation at Cold Spring Harbor Lavoratory meeting "Neurobiology of Drosophila" on October 2nd, 2015.
Moto gave a talk in the Advanced ICT symposium at Tokyo Big Sight on January 27th, 2016
Moto gave a talk at Engineering Science in Osaka University on October 24th, 2016.
Moto gave a presentation and served as a chairperson at Society for Neuroscience in San Diego on November 11th, 2016.
Moto Yoshihara, principal investigator.
Moto Yoshihara received his B. Sc. (1987) from the Department of Zoology at the University of Tokyo and Ph.D. (1992) from the Department of Biological Chemistry at the University of Tokyo, Japan. He received a Human Frontiers Science Program fellowship to do postdoctoral work at the City of Hope, California in the laboratory of Kazuo Ikeda. After working as a visiting scientist at the Massachusetts Institute of Technology, he joined the Department of Neurobiology at the University of Massachusetts Medical School as a faculty member in 2006. In 2013, he left University of Massachusetts Medical School to work as a visiting professor at MIT, being supported by NIH grant, R01. In 2014, he moved back to Japan, and joined National Institute of Information and Communications Technology as a Senior Research Scientist (PI).
Shinya and Moto, the main force for publication of the Feeding neuron paper
in the announce from UMass when our paper appeared on Nature
Contact; Moto Yoshihara, Ph.D.
Memory Neurobiology Project
Advaced ICT Research Institute ("NICT Kobe")
National Institute of Information and Communiocations Technology,
588-2 Iwaoka, Nishi-ku