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Assistant Professor of Molecular Physiology and Biophysics
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MD, Tohoku University School of MedicinePh.D. course student, Tokyo University School of Medicine, Tokyo, JapanPhD, Neuropathology, Tohoku University School of Medicine
Board Certification National board of physicians, Japan ECFMG certificate English Commission for Foreign Medical Graduates: National board of physicians, U.S.A.
Biosciences Graduate ProgramDepartment of Molecular Physiology and Biophysics PhDInterdisciplinary Graduate Program in NeuroscienceMedical Scientist Training Program
My laboratory focuses on the study of synaptic transmission in the mammalian central nervous system (CNS), with a particular interest in presynaptic mechanisms and the modulation of neurotransmitter release. The long-term goal of our research is to understand how synaptic transmission is regulated, and how its disruption contributes to neurological and psychiatric disorders.
Research performed over several decades has provided us with an extensive outline of synaptic communication between neurons. We know that the neurotransmitter synthesized in the nerve terminals of a presynaptic neuron is loaded into synaptic vesicles, after which an action potential arriving at the nerve terminal triggers calcium-dependent fusion between synaptic vesicles and the presynaptic membrane—culminating in neurotransmitter release from the nerve terminal. This release allows neurotransmitter to diffuse through the intercellular space (synaptic cleft) toward the postsynaptic membrane, on which neurotransmitter receptors are concentrated. Stimulation of those receptors by neurotransmitter, in turn, leads to the opening of receptor-ion channel complexes and to the initiation of intracellular signaling. This is followed by the removal of neurotransmitter from the synaptic cleft, either by cellular uptake or enzymatic destruction, to complete the cycle. Any change in this long cascade of events can modify the efficiency of synaptic transmission. When a change occurs under physiological conditions, it can result in learning, memory formation or forgetting; when it occurs under pathological conditions, it may lead to disorders.
In spite of this impressive description of neuronal signaling, many unanswered questions remain. For example, what determines the concentration of neurotransmitter inside a vesicle? What determines the likelihood of its release from a nerve terminal? Just how do vesicles fuse with a membrane in a particular situation to achieve the amount of neurotransmitter that is called for? How fast and how far does released neurotransmitter travel? How are these parameters altered in various disease states?
This is a wonderful time for us to be exploring these questions, as fluorescence imaging, electrophysiological technology and electron microscopy are at stages where they can be combined in new ways, and used to look at processes at new, molecular levels of detail. In particular, we can visualize a group of molecules in single synaptic vesicles. With this new approach in hand, we are literally “watching” the miracle of vesicle fusion in cultured rodent neurons as it occurs. Our studies should provide fresh insights into an old, but ever fascinating, field of research.
Date Last Modified: 06/07/2014 -
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