Laboratory for Memory and Learning

Masao ITO, M.D., Ph.D.
Laboratory Head

Main Publications at RIKEN

Research Areas

Within the brain, numerous neurons form elaborate neuronal circuits, which displays subtle functions of our brain. How this can happen has been the central question I addressed in my research for the past 5 decades. Since we discovered the exclusively inhibiotory action of cerebvellar Purkinje cells in 1964, the cerebellum has been our major research field. In 1979, we revealed the mechanism of the vestibuoolcuar reflex as a cerebellum-controlled adaptive system. In 1982，we discovered long-term depression LTD as the major mechanism of cerebellar adaptation, and since then continued to study cellular, molecularmechanisms of LTD in cerebellar slices or tissue culture. The major target has been protein kinase G and its sopeciufic substrate (G-Substrate), protein phosphatase 2A, phospholipase A2a etc. This line of work is still going on with orexins and JunB as major targets. Since 1990, in parallel with these works, I have been trying to hypothesize that the cerebellum copies a concept or idea originally formed in the cerebral cortex, and then one can think unconsciously by manipulating these copies in the cerebellum. This is a guiding hypothesis for the Shogi project that wehave started since 2007 in colaboration with Shogi-Renmei and Fujitsu.

Mechanisms of LTD and learning in the cerebellum. (Ref. 3)

Research Subjects

Molecular mechanisms of cerebellar LTD
Control mechanisms of mental activities by the cerebellum
Roles of the cerebellum in Shogi play

Selected Publications

Ito, M.:
"Control of mental activities by internal models in the cerebellum."
Nature Reviews Neuroscience AOP, published online, doi:10.1038/nrn2332. (2008).
Ito, M.:
"Cerebellar circuitry as a neuronal machine."
Prog. Neurobiol. 78, 272-303, (2006).
Tatsukawa, T., Chimura, T., Miyakawa, H., and Yamaguchi, K.:
"Involvement of basal protein kinase C and extracellular signal-regulated kinase 1/2 activities in constitutive internalization of AMPA receptors in cerebellar Purkinje cells."
J. Neurosci., 26(18): 4820 – 482, (2006).
Ito, M.:
"Bases and implications of learning in the cerebellum - Adaptive control and internal model mechanism."
Progr. in Brain Res. "Creating Coordination in the Cerebellum". ed. C. De Zeeuw. 148, 95-109, (2005).
Koekkoek, S.K., Yamaguchi, K., Milojkovic, B.A., Dortland, B.R., Ruigrok, T.J., Maex, R., DeGraaf, W., Smit, A.E., Vanderwerf, F., Bakker, C.E., Willemsen, R., Ikeda, T., Kakizawa, S., Onodera, K., Nelson, D.L., Mientjes, E., Joosten, M., De Schutter, E., Oostra, B.A., Ito, M, and DeZeeuw, C.I.:
"Deletion of FMR1 in Purkinje Cells Enhances Parallel Fiber LTD, Enlarges Spines, and Attenuates Cerebellar Eyelid Conditioning in Fragile X Syndrome."
Neuron. 47:339-352, (2005).
Shirai, Y., and Ito, M.:
"Specific differential expression of phospholipase A(2) subtypes in rat cerebellum."
J. Neurocytol. 33: 297-307, (2004).
Launey, T., Endo, S., Sakai, R., Harano, J., and Ito, M.:
"Protein phosphatase 2A inhibition induces cerebellar long-term depression and declustering of synaptic AMPA receptor."
Proc. Natl Acad. Sci. USA. 101: 676-81, (2004).
Endo, S., Nairn, A.C., Greengard, P., and Ito, M.:
"thr 123 of rat G substrate contributes to its action as a protein phosphatase inhibitor."
Neurosci. Res., 45, 79-89, 2003.
M. Ito.:
"The molecular organization of cerebellar long-term depression."
Nature Reviews Neuroscience 3, 896-902, (2002).
Karachot, L., Shirai, Y., Vigot, R., Yamamori, T., and Ito, M.:
"Induction of long-term depression in cerebellar Purkinje cells requires a rapidly turned over protein."
J. Neurophysiol. 86, 280-289, (2001).

Main Publications at RIKEN

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