Education

•    B.A. Gifu Pharmaceutical University, Gifu, JAPAN (Pharmacology)
•    Ph.D. Kyushu University, Fukuoka, JAPAN (Pharmacology)

Postdoctoral Training

•    Postdoctoral Fellow, Cold Spring Harbor Laboratory, Cold Spring Harbor , NY
      (PI: Dr. Alcino J. Silva)
•    Visiting Assistant Researcher, Department of Neurobiology and Brain Research Institute, UCLA,
      Los Angeles, CA (PI: Dr. Alcino J. Silva)

Awards

•    1989-1991 Research Award from the Japan Society for the Promotion of Science (JSPS)
•    1992 Mochida Memorial Foundation Research Fellowship Award
•    1998 Uehara Memorial Foundation Research Fellowship Award

Research Interests

The major focus of my research is on (1) understanding molecular, cellular, and systems foundations of learning & memory and (2) establishing the therapeutic strategies to improve and/or prevent the progression of cognitive disorders associated with Alzheimer’s disease or normal aging.

With the aging of our population, therapeutic interventions of cognitive disorders or dementia are becoming one of the most crucial facets of public health. Elucidating mechanisms by which information is encoded, stored and recalled in normal brain and understanding how these processes are impaired in disease conditions work cooperatively like the two wheels in order to unequivocally validate potential therapeutic approaches for the treatment of human cognitive impairments. Modern behavioral, biophysical and molecular genetics of the mouse provides a powerful tool to address these problems. In our laboratory, we apply a combination of molecular biology, biochemistry, electrophysiology, and behavioral assays to genetically engineered mouse models that lack or overexpress specific genes. These multidisciplinary analyses of mutant mice synergistically favor our tackling divergent aspects of learning & memory and their impairments. Specifically, my research projects include: (1) synaptic and nuclear signaling mechanisms (e.g., CaMKII, MAPK, CREB, etc.) as molecular substrates of learning & memory and related cellular events (e.g., LTP, neuron excitability, neurogenesis, etc.); (2) functional consequences of the b-secretase (BACE1) manipulations in Alzheimer model mice, in particular, neural mechanisms for memory rescue by BACE1 inhibition leading to the development of disease-altering therapeutic treatments for Alzheimer’s disease.

Selected Publications

P.W. Frankland, C. O'Brien, M. Ohno, A. Kirkwood and A.J. Silva. a-CaMKII-dependent plasticity in the cortex is required for permanent memory. Nature, 411, 309–313 (2001)
•    This article was featured by “news and views” in Nature 411, 248–249 (2001).

M. Ohno, P.W. Frankland, A.P. Chen, R.M. Costa and A.J. Silva. Inducible, pharmacogenetic approaches to the study of learning and memory. Nat. Neurosci., 4, 1238–1243 (2001)
•    This article was featured by “Research Update” in TINS 25, 277–279 (2002).

R.M. Costa, N.B. Fedorov, J.H. Kogan, G.G. Murphy, J. Stern, M. Ohno, R. Kucherlapati, T. Jacks and A.J. Silva. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature, 415, 526–530 (2002)

M. Ohno, P.W. Frankland and A.J. Silva. A pharmacogenetic inducible approach to the study of NMDA/aCaMKII signaling in synaptic plasticity. Curr. Biol., 12, 654–656 (2002)

M. Ohno, E.A. Sametsky, L.H. Younkin, H. Oakley, S.G. Younkin, M. Citron, R. Vassar and J.F. Disterhoft. BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer’s disease. Neuron, 41, 27–33 (2004)
•    This article was featured by “news and views in brief” in Nature 427, 210 (2004).

G.G. Murphy, N.B. Fedorov, K.P. Giese, M. Ohno, E. Friedman, R. Chen and A.J. Silva. Increased neuronal excitability, synaptic plasticity, and learning in aged Kvβ1.1 knockout mice. Curr. Biol., 14, 1907–1915 (2004)

J.F. Disterhoft, W.W. Wu and M. Ohno. Biophysical alterations of hippocampal pyramidal neurons in learning, ageing and Alzheimer's disease. Ageing Res. Rev., 3, 383–406 (2004)

M. Ohno, W. Tseng, A.J. Silva and J.F. Disterhoft. Trace eyeblink conditioning requires the hippocampus but not autophosphorylation of aCaMKII in mice. Learn. Mem., 12, 211–215 (2005)

A.P. Chen, M. Ohno, K.P. Giese, R. Kühn, R.L. Chen and A.J. Silva. Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory. J. Neurosci. Res., 83, 28–38 (2006)

M. Ohno, L. Chang, W. Tseng, H. Oakley, M. Citron, W.L. Klein, R. Vassar and J.F. Disterhoft. Temporal memory deficits in Alzheimer's mouse models: rescue by genetic deletion of BACE1. Eur. J. Neurosci., 23, 251–260 (2006)

M. Ohno, E.A. Sametsky, A.J. Silva and J.F. Disterhoft. Differential effects of aCaMKII mutation on hippocampal learning and changes in intrinsic neuronal excitability. Eur. J. Neurosci., 23, 2235–2240 (2006)

H. Oakley, S.L. Cole, S. Logan, E. Maus, P. Shao, J. Craft, A. Guillozet-Bongaarts, M. Ohno, J. Disterhoft, L. Van Eldik, R. Berry and R. Vassar. Intraneuronal β-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation. J. Neurosci., 26, 10129–10140 (2006)

M. Ohno. Genetic and pharmacological basis for therapeutic inhibition of β- and g-secretases in mouse models of Alzheimer’s memory deficits. Rev. Neurosci. (in press)

M. Ohno and J.F. Disterhoft. Alzheimer’s disease therapies: updates on genetic and pharmacological manipulations of β-secretase. In M.-K. Sun (Ed.), Research Progress in Alzheimer’s Disease and Dementia, Novaf Science Publishers, New York (in press)

M. Ohno, S.L. Cole, M. Yasvoina, J. Zhao, M. Citron, R. Berry, J.F. Disterhoft and R. Vassar. BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Neurobiol. Dis. (submitted)

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The Ohno Lab