2000 Fiscal Year Final Research Report Summary
Molecular mechanisms of synaptic plasticity : specific involvement of various aspects of calcium dependent processes
| Project/Area Number |
09480229
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KATO Nobuo Kyoto University, Graduate School of Medicine, associate professor, 医学研究科, 助教授 (10152729)
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| Project Period (FY) |
1997 – 2000
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| Keywords | Long-term potentiation / Long-term depression / Synaptic plasticity / calcium release |
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| Research Abstract |
In neurons and non-excitable cells alike, single intracellular signaling molecules seem to be involved in more than one signaling cascade, so as to mediate more than one intracellular messages. How the same signal molecule tells two or more biologically different contents of intracellular messages is puzzling. One fruitful approach to address this puzzle would be to study the mechanism of bi-directional regulation of synaptic plasticity in neurons, which is dependent on the calcium ion. Long-term potentiation (LTP) and depression (LTD), which represent up- and down-regulations of synaptic efficiency respectively, are widely accepted models for studying molecular mechanisms of memory. Increases of intracellular Ca2+ concentration are required for induction of both LTP and LTD.These two types of synaptic regulations are shown to be discriminately induced, depending on the same intracellular Ca2+ ions. The findings obtained in the present project suggest that intracellular Ca2+ can carry
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sufficient information to initiate discriminative induction of LTP or LTD.The present project discovered a novel form of calcium release, which is caused by a synergistic activation of the IP_3 receptors on the endoplasmic reticulum by its two ligands calcium and IP_3. This novel calcium release was further demonstrated to correlate with an activity-dependent, negative feedback regulation of action potential firing. These findings seem to have a number of implications on neocortical physiology. First, a novel anchor molecule might exist which links IP3 receptors and voltage-dependent calcium channels. Second, the present novel calcium release may provide a site of interaction between the "slow", neuromodulator-dependent cortical projection system and the "fast" system, which most directly affects intracellular calcium concentration. Third, this novel calcium release may prevent excitotoxic neuronal death without preventing basic neuronal activity, and could therefore be therapeutically useful. The last possibility was experimentally supported in the present study. Less
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