Kimiko Shimizu, Ph.D.
清水 貴美子Title: Professor
Address: 3190 Gofuku, Toyama 930-8555, JAPANUniversity of Toyama
Organization for International Education and Exchange
Email: kshimizu@ctg.u-toyama.ac.jp
https://researchmap.jp/kimikoshimizu
https://orcid.org/0000-0003-4943-2552
Additional post
・Project Researcher in The University of Tokyo (Center for Disease Biology and integrative Medicine)
Email: shimizuk@g.ecc.u-tokyo.ac.jp
・Visiting lecturer in Toho University (Medical school)

Research Keyword
circadian rhythm, SCOP, Ras-MAPK, learning & memory, anxiety, neurosteroids, spine,biochemistry, molecular biology, behavior, mouse, monkey
Research Overview
I investigate circadian changes in memory and emotion and their molecular mechanisms in mice. Using
behavioral, biochemical, molecular biological, and genetic methods, I systematically elucidate memory andemotion's molecular and physiological functions through multi-level experiments from molecular to behavioral
analysis.
Circadian clocks control long-term recognition memory formation
in a circadian manner. Disruption of the central clock (hypothalamicsuprachiasmatic nucleus) or the hippocampal clock (loss of clock
molecules in the hippocampus) lose circadian change in long-termmemory. Circadian variation in the amount of SCOP in thehippocampal lipid rafts regulates the K-Ras-ERK/MAPK-CREB
pathway. It produces diurnal rhythm in long-term memory
performance (Nat. Commun. 7, 12926, 2016). Anxiety-like behavior
in mice also has a circadian rhythm. It is controlled by the circadianclock and SCOP in the amygdala (Sci. Rep. 6, 33500, 2016).
Novel neurosteroids, 7α-hydroxypregnenolone and 7αhydroxydehydroepiandrosterone, are synthesized in the mouse brain
after spatial learning. These steroids contribute to remote memory
via remodeling dendritic spines in hippocampal neurons (iScience 23, 101559, 2020).

Selected Publications
Shimizu K.*, Inoue S., Oishi T., Takada M., Fukada Y., and Imai H. Diurnal variation in declarative memory
and the involvement of SCOP in cognitive functions in nonhuman primates. Molecular Brain 16: 31(2023) DOI: 10.1186/s13041-023-01022-0
Takeuchi S., Shimizu K., Fukada Y., and Emoto K. The circadian clock in the piriform cortex intrinsically tunes
daily changes of odor-evoked neural activity. Commun. Biol., 6: 332 (2023) DOI: 10.1038/s42003-02304691-8
Maehata K., Shimizu K.*, Ikeno T., Wang Q., Sakurai A., Wei Z., Pan Y., Takao T., Fukada Y.* Hippocampal
7α-hydroxylated neurosteroids are raised by training and bolster remote spatial memory with increase of thespine densities. iScience 23, 101559 (2020) DOI:10.1016/j.isci.2020.101559
Wang Q., Shimizu K., Maehata K., Pan Y., Sakurai K., Hikida T., Fukada Y., and Takao T.* Lithium ion
adduction enables UPLC-MS/MS-based analysis of multi-class 3-hydroxyl group-containing keto-steroids.
Journal of Lipid Research 61, 570-579 (2020) DOI: 10.1194/jlr.D119000588
Shimizu, K.*, Fukada, Y. Stereotaxic surgery for suprachiasmatic nucleus lesions in mice. Bio-protocol 7:2346 (2017) DOI:10.21769/bioprotoc.2346
Shimizu, K*, Kobayashi, Y., Nakatsuji, E., Yamazaki, M., Shimba, S., Fukada, Y.* SCOP/PHLPP1b mediates
circadian regulation of long-term recognition memory. Nature communications 7: 12926 (2016)
DOI:10.1038/ncomms12926
Nakano, J., Shimizu, K.*, Shimba, S., Fukada, Y.* SCOP/PHLPP1β in the basolateral amygdala regulates
circadian expression of mouse anxiety-like behavior. Scientific Reports 6: 33500 (2016)
DOI:10.1038/srep33500
Shimizu, K., Mackenzie, S. M., and Storm, D.R. SCOP/PHLPP and its functional role in the brain.
Molecular Biosystems 6: 38-43 (2010) DOI:10.1039/B911410F
Shimizu, K., Phan, T., Mansuy, I.M. and Storm, D.R.* Proteolytic Degradation of SCOP in the Hippocampus
Contributes to Activation of MAP Kinase and Memory. Cell 128: 1219-1229 (2007)
DOI:10.1016/j.cell.2006.12.047
Cheng, H-Y. M., Papp, J. W., Varlamova, O., Dziema, H., Russell, B., Curfman, J.P., Nakazawa, T., Shimizu, K.,
Okamura, H., Impey, S., and Obrietan, K.* microRNA Modulation of Circadian-Clock Period andEntrainment. Neuron 54: 813-829 (2007) DOI:10.1016/j.neuron.2007.05.017
Shimizu, K., Okada, M., Nagai, K. and Fukada, Y.* Suprachiasmatic nucleus circadian oscillatory protein, anovel binding partner of K-Ras in the membrane rafts, negatively regulates MAPK pathway. J. Biol. Chem.
278: 14920-14925 (2003) DOI:10.1074/jbc.M213214200
Takano, A., Shimizu, K., Kani, S., Buijs, R.M., Okada, M. and Nagai, K.* Cloning and characterization of rat
casein kinase Ie. FEBS letters 477: 106-112 (2000) DOI:10.1016/S0014-5793(00)01755-5
Shimizu, K.*, Okada, M., Takano, A. and Nagai, K. SCOP, a novel gene product expressed in a circadianmanner in rat suprachiasmatic nucleus. FEBS letters 458: 363-369 (1999) DOI:10.1016/S00145793(99)01190-4
Shimizu, K., Nagai,N. and Nakagawa, H.* An immunotoxin, anti-VIP antibody-ricin A chain conjugate,
eliminates neurons in the hypothalamic suprachiasmatic nucleus selectively and abolishes the circadian rhythmof water intake. Brain Res. Bull. 41: 369-378 (1996)
Shimizu, K., Hibino, H., Komenami, N., Nagai, N., Nagai, K. and Nakagawa, H.* Permissive effect of VIP on
the hyperglycemic response induced by 2-deoxy-D-glucose. Neurosci. Lett. 175: 157-160 (1994)