Toyo University
Laboratory for Molecular Neurobiology
Research Aim
Synaptic plasticity underlies learning and memory
The neurons in the brain are connected with each other at synapses to form neural circuits. It is known that, unlike electronic circuits, neural circuits are flexible and can be modified by various experiences and environments. This flexibility is known as "synaptic plasticity".
Although it has been well studied in the field of neuroscience, the mechanism of synaptic plasticity is still largely unknown. We believe that elucidation of the mechanism of synaptic plasticity will lead not only to a better understanding of the fundamental principles of brain functions, but also to the understanding of various neuropsychiatric diseases, likely allowing for the development of new therapeutic methods.
Message
Nobuhiko Kojima, Professor
How is the mind created, where and how does the mind exist?
It is now well accepted that the mind is created in the brain, not in the heart. Like any other organs, the brain is composed of cells and molecules. Genes, the blueprints of life, generate molecules that govern the synaptic connection among neurons and create complex neural networks. Thus, the synapses, as a place of information processing, are critical for creating the mind.
A large number of molecules accumulate at the synapse and support synaptic functions. However, the molecular mechanism underlying synaptic functions is not fully understood yet. Unlike electronic circuits, neural circuits can be added, lost or changed through various experiences. This unique feature of the brain, known as "plasticity," enables learning and memory. However, disturbance in the plasticity may cause various psychiatric disorders.
We aim to clarify the molecular mechanism of synaptic plasticity, which can be considered as a neural basis of the mind, by investigating the synaptic functions at a molecular, cellular, and behavioral levels.
For applicants
Different from electrical circuits, the synaptic connections in the brain are variable and are the fundamentals of the plastic structure of the brain. Although synaptic plasticity is a well-established phenomenon, the underlying molecular mechanisms remain largely unknown. However, there is considerable scope for further research. Hence, for those who wish to join us, we would like you to explore these mechanisms with a creative and challenging spirit that is not bound by existing concepts.
Research Themes
1. The function of actin cytoskeletal protein in dendritic spines
The dendritic spines is known as major postsynaptic sites, and the shape of dendritic spine is supported by actin cytoskeleton. We focus on drebrin, a spine-resident side-binding protein of F-actin, which is thought to be involved in learning and memory as well as in cognitive impairment caused by Alzheimer's disease. We have studied the functional role of drebrin in dendritic spines, and have also explored novel binding partners of drebrin.
2. Synaptic abnormalities in animal models of neuropsychiatric disorders
We have studied the relationship between behavioral abnormalities and the morphology/function of
brain synapses, using animal models of stress-induced neuropsychiatric disorders (e.g., human
depression and post traumatic stress disorder) or developmental disorders such as autism spectrum
disorder.
Original article
2021
Mizuno Y, Konishi S, Imai H, Fujimori E, Kojima N, Kajiwara C, Yoshinaga J
"Telomere length and urinary 8-hydroxy-2’-deoxyguanosine and essential trace element concentrations in female Japanese university students."
J Environmental Science and Health (Part A) 56:1328-1334.2021
Seidl MD, Fels B, Kranick D, Sternberg A, Grimm K, Stümpel FT, Pluteanu F, Schulte JS, Heinick A, Kojima N, Endo S, Huge A, Stoll M, Müller FU
"Induction of ICER is superseded by smICER, challenging the impact of ICER under chronic beta-adrenergic stimulation."
FASEB Journal doi: 10.1096/fj.201902301RR.2019
Mizuno Y, Konishi S, Imai H, Fujimori E, Kojima N, Yoshinaga J
"Cadmium exposure and blood telomere length in female University students in Japan."
Biol Trace Elem Res doi: 10.1007/s12011-019-1656-3.2018
Yasuda H, Kojima N, Hanamura K, Yamazaki H, Sakimura K, Shirao T.
"Drebrin isoforms critically regulate NMDAR- and mGluR-dependent LTD induction."
Front Cell Neurosci 12: 330.2018
Bohn T, Rapp S, Luther N, Klein M, Bruehl T-J, Kojima N el al.
"Tumor immunoevasion via acidosis dependent induction of regulatory tumor-associated macrophages."
Nature Immunol 19: 1319–1329.2018
Hanamura K, Kamata Y, Yamazaki H, Kojima N, Shirao T.
"Isoform-dependent regulation of drebrin dynamics in dendritic spines."
Neuroscience 379: 67–76.2017
Kajita Y, Kojima N, Koganezawa N, Yamazaki H, Sakimura K, Shirao T.
"Drebrin E regulates neuroblast proliferation and chain migration in the adult brain."
Eur J Neurosci 46: 2214–2228.2016
Kojima N, Yasuda H, Hanamura K, Ishizuka Y, Sekino Y, Shirao T.
"Drebrin A regulates hippocampal LTP and hippocampus-dependent fear learning in adult mice."
Neuroscience 324: 218–226.2016
Puspitasari A, Koganezawa N, Ishizuka Y, Kojima N, Tanaka N, Nakano T, Shirao T.
"X-irradiation induces acute cognitive decline via transient synaptic dysfunction."
Radiation Research 185: 423–430.2015
Maekawa M, Iwayama Y, Ohnishi T, Toyoshima M, Shimamoto C, Hisano Y, Toyota T, Balan S, Matsuzaki H, Iwata Y, Takagai S, Yamada K, Ota M, Fukuchi S, Okada Y, Akamatsu W, Tsujii M, Kojima N, Owada Y, Okano H, Mori N, Yoshikawa T.
"Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism."
Scientific Reports 5: 16239.2014
Yamazaki H, Kojima N, Kato K, Hirose H, Iwasaki T, Mizui T, Takahashi H, Hanamura K, Roppongi RT, Koibuchi N, Sekino Y, Mori N, Shirao T.
"Spikar, a novel drebrin-binding protein, regulates the formation and stabilization of dendritic spines."
Journal of Neurochemistry 128: 507–522.2014
Mizui T, Sekino Y, Yamazaki H, Ishizuka Y, Takahashi H, Kojima N, Kojima M and Shirao T.
"Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines."
PLoS ONE 9: e85367.2013
Roppongi RT, Kojima N, Hanamura K, Yamazaki H, Shirao T.
"Selective reduction of drebrin and actin in dendritic spines of hippocampal neurons by activation of 5-HT(2A) receptors."
Neuroscience Letters 547: 76–81.
Conference
2021 Jul
Yoshida A, Kojima N.
"Impaired olfactory-dependent neural activity in drebrin knockout mice."
The 44th Annual Meeting of the Japan Neuroscience Society/The 1st CJK International Meeting (Online meeting)2020 Mar
Kato R, Kojima N.
"Heat stress-induced cognitive dysfunction is caused by changes in the gut microbiota. "
The 98th Annunal Meeting of the Physiological Society of Japan(Web meeting)2020 Mar
Sawabe M, Kojima N.
"Changes in spine morphology and learning behavior in drebrin knockout mice."
The 98th Annunal Meeting of the Physiological Society of Japan(Web meeting)2019 Mar
Kojima N, Sawabe M, Shu Kaiin, Hanamura K, Shirao T.
"The activity of metabotropic glutamate receptor affects drebrin localization in dendritic spines."
9th FAOPS congress Kobe2018 Sep
Shiraishi K, Kojima N.
"Prenatal exposure to sodium valproate causes synaptic abnormality and gene expression changes in the brain."
WFSBP 2018 Kobe2017 Jul
Shiraishi K, Urushiyama R, Yamazaki R, Kaneko S, Oka Y, Kojima N.
"Prenatal exposure of mice to sodium valproate causes synaptic abnormality and change in gene expression in the brain."
The 40th Annual Meeting of the Japan Neuroscience Society, Makuhari Messe2017 Jul
Kojima N, Yasuda H, Sakimura K, Shirao T.
"Impact of drebrin-knockout on mGluR5- and NMDAR-dependent LTD induction in the hippocampus."
The 40th Annual Meeting of the Japan Neuroscience Society, Makuhari Messe2016 Jul
Kakegawa R, Shiraishi K, Kojima N.
"Impact of molecular interactions of metabotropic glutamate receptor and drebrin on synaptic structural plasticity in hippocampal neurons."
The 39th Annual Meeting of the Japan Neuroscience Society, PACIFICO Yokohama2015 Sep
Kakegawa R, Kamasaki S, Todoriki T, Kojima N.
"The role of metabotropic glutamate receptor on structural plasticity of dendritic spines in cultured hippocampal neurons."
Domestic conference2015 Sep
Kajita Y, Koganezawa N, Kojima N, Sakimura K, Sakurai T, Shirao T.
"Drebrin knockout mice show olfactory dysfunction by impairment of adult neurogenesis and cell survival."
Domestic conference2015 Sep
Yasuda H, Kojima N, Hanamura K, Shirao T.
"Drebrin knockout mice show olfactory dysfunction by impairment of adult neurogenesis and cell survival."
Domestic conference2015 Jul
Kajita Y. Koganezawa N, Kojima N, Sakimura K, Shirao T.
"Drebrin knockout mice show the impairment of olfaction and adult neurogenesis."
The 38th Annual Meeting of the Japan Neuroscience Society, Kobe convention center2014 Nov
Puspitasari A, Koganezawa N, Kojima N, Isono M, Yoshida Y, Shirao T.
"Acute effect of X-irradiation and carbon ion-irradiation on fear memory formation and its underlying mechanism."
The 41st Annual meeting of Society for Neuroscience, Walter E. Washington Convention Center, Washington, DC.2014 Sep
Kojima N.
"Maturation of cytoskeletal molecules in neurons: Drebrin is a key molecule for synaptic plasticity."
ISN satellite symposium on "Key molecules for neuronal maturation", The University of Tokyo2014 Sep
Koganezawa N, Puspitasari A, Kojima N, Isono M, Yoshida Y, Shirao T.
"The time-dependent effects of radiation on fear memory and synaptic proteins."
Domestic conference2014 Sep
Kajita Y, Kojima N, Sakimura K, Shirao T.
"Drebrin knockout mice show the olfaction impairment caused by delayed neural exchange in olfactory bulb."
The 37th Annual Meeting of the Japan Neuroscience Society, PACIFICO Yokohama2014 Sep
Koganezawa N, Kajita Y, Kojima N, Sakimura K, Shirao T.
"Primary cultured hippocampal neurons prepared from drebrin knockout mouse shows the decrease of MAP2 positive dendrites at late developmental stage."
The 37th Annual Meeting of the Japan Neuroscience Society, PACIFICO Yokohama2014 Sep
Puspitasari A, Koganezawa N, Kojima N, Isono M, Yoshida Y, Shirao T.
"Acute effect of carbon ion irradiation on hippocampal neuronal cell death and fear memory formation."
The 37th Annual Meeting of the Japan Neuroscience Society, PACIFICO Yokohama2014 Sep
Puspitasari A, Koganezawa N, Shuchuan M, Kojima N, Isono M, Yoshida Y, Kanai T, Shirao T.
"Acute effect of Carbon Ion Irradiation on hippocampal neuron and fear memory formation."
The 6th ISN 2014 Special Neurochemistry Conference, The University of Tokyo2014 Sep
Shirao T, Koganezawa N, Kajita Y, Kojima N, Sakimura K.
"Primary cultured neurons prepared from drebrin knockout mice have a few MAP2 positive dendrites."
Domestic conference2013 Nov
Puspitasari A, Koganezawa N, Kojima N, Shirao T.
"Acute effects of X-irradiation on learning, adult neurogenesis and the accumulation of drebrin."
The 40th Annual meeting of Society for Neuroscience, San Diego Convention Center, California2013 Oct
Kajita Y, Kojima N, Sakimura K, Shirao T.
"Impairment of Adult Neurogenesis by Drebrin Knockout Results in the Olfactory Dysfunction."
Brain and Health Informatics 2013, Maebashi TERRSA2013 Jun
Puspitasari A, Koganezawa N, Kojima N, Shirao T.
"Effect of X-irradiation on learning, cell death and synaptic proteins."
Domestic conference2013 Jun
Kajita Y, Kojima N, Sakimura K, Shirao T.
"Drebrin knockout mice show the impairment of olfactory acuity via affecting adult neurogenesis."
Domestic conference2013 Apr
Kojima N.
"Molecular and neuronal regulation of emotional memory: Age-related vulnerability to synaptic dysfunction in drebrin A-knockout mice."
24th Biennial Meeting symposium, International Society for Neurochemistry, Cancun, Mexico