Satoshi FUJII

Professor, Physiology
Facutly of Medicine


Degree M.D. Akita University School of Medicine, 1984
Graduete Programs Neurobiology and Behavior

Cellular and Molecular Neurophysiology; purinergic or glutamatergic control of synaptic plasticity; activity-dependent modification of synaptic plasticity; functional interaction between glia and neurons.

Activity-dependent modification of synaptic efficacy is fundamental to the storage of information in the brain. Long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus are long-lasting changes in synaptic efficacy and are thought to play an important role in learning and memory. My research focuses on purinergic or glutamatergic control of synaptic plasticity in the hippocampus with the goal of identifying molecular mechanisms for cognitive impairment.
The activity-dependent LTP at CA1 synapses is generally believed to be triggered by the influx, during high frequency stimulation (HFS), of calcium ions (Ca2+) into the post-synaptic neuron through channels coupled to N-methyl-D-aspartate (NMDA) glutamate receptors. Furthermore, LTD, the depression of a response by low-frequency afferent stimulation (LFS) in a naive CA1 input pathway, is blocked by NMDA receptor (NMDAR) antagonists. Thus, activation of NMDARs during HFS or LFS is an essential factor in the induction of activity-dependent LTP or LTD in CA1 neurons. Activation of metabotropic glutamate receptors (mGluRs) is believed to be a significant functional component of the cellular mechanisms of LTP or LTD induction in the hippocampus@However, it is not known how CA1 synaptic inputs activate NMDARs and/or mGluRs to decide the direction of synaptic plasticity, i.e., potentiation or depression.@We suggest that activation of protein kinase C or inositol-1,4,5-trisphosphate receptors, both coupled to group 1 mGluRs, may determine the direction (potentiation or depression) of synaptic plasticity of the response at CA1 synapses.

Adenosine 5'-triphosphate (ATP), a common constituent of synaptic vesicles which is released mainly as a co-transmitter together with noradrenaline, acetylcholine, or other substances, enters hippocampal CA1 neuron synapses following electrical stimulation of Schaffer collaterals. In CA1 neurons, LTP can be induced by extracellular application of ATP (ATP-induced LTP) during test electrical stimulation delivered at 0.05 Hz. We investigate the role of ATP in the mechanism involved in ATP-induced LTP was studied. We have shown that, in ATP-induced LTP in CA1 neurons, extracellularly applied ATP provides enough substrate for ecto-protein kinase to induce LTP via the extracellular phosphorylation of synaptic membrane proteins. We suggest that one such protein substrate for ecto-protein kinases in ATP-induced LTP could be the NMDA receptor / Ca2+ channel. Since LTP induction in CA1 neurons involves intracellular second messenger systems which are triggered by a large Ca2+ influx into the cell through NMDA receptors / channels, and since activation of NMDA receptors / channels is a necessary step in producing ATP-induced LTP, phosphorylation of NMDA receptors / channels allows a large Ca2+ influx into the cell to activate intracellular second messenger systems to produce ATP-induced LTP.

Original articles (1996-2016)