Summary of Research Project Results Under the JSPS FY2000
"Research for the future Program"



1.Research Institution Okazaki National Research Institutes
 
2.Research Area Life Science
 
3.Research Field Higher Brain Functions
 
4.Term of Project FY1996〜FY2000
 
5.Project Number 96L00207
 
6.Title of Project Molecular biological studies on neural plasticity and long-term memory

7.Projetct Leader
Name Institution,Department Title of Position
IMOTO, Keiji National Institute for Physiological Sciences Professor

8.Core Members

Names Institution,Department Title of Position
MORI, Yasuo National Institute for Physiological Sciences Associate Professor
NAKAI, Junichi National Institute for Physiological Sciences Research Associate
WAKAMORI, Minoru National Institute for Physiological Sciences Research Associate

9.Cooperating Researchers

Names Institution,Department Title of Position
MORI, Masayuki National Institute for Physiological Sciences JSPS Fellow
HUDA, Kadrul National Institute for Physiological Sciences JSPS Fellow
YAMADA, Hisanobu National Institute for Physiological Sciences JSPS Fellow

10.Summary of Research Results

In this project, we made comprehensive studies on calcium metabolism, which is directly related to neuronal plasticity and long-term memory in neurons. We conducted molecular biological analyses of voltage-gated calcium channels, which are a major calcium influx pathway to neurons. Particularly, we investigated the molecular mechanism of hereditary ataxia caused by calcium channel mutations. Disorders in calcium metabolism can result in not only primary effects of various severity but also various secondary effects, which include up- and downregulation of related functional molecules such as glutamate receptors. We also analyzed the operational mechanism of TRP channels, which are an architypal receptor-activated calcium-permeable cation channels. TRP channels are widely distributed, and relatively abundantly expressed in the brain. TRP channels can be activated by many kinds of modulators, including calcium ions. We could obtain no direct evidence to support that TRP channels are activated by depletion of the intracellular calcium stores. As for the physiological role, we demonstrated TRP channels play an essential role in contraction by agonists in smooth muscle. Functions in neurons are now under investigation. For improvement of measuring techniques, we developed a protein module that specifically binds to IP3. Furthermore, we succeeded to improve a GFP-based calcium sensor, which is much brighter and much more sensitive than a prototype sensor molecule. We built a two-photon excitation laser microscope. We could observe fine structures, like dendritic spines, more easily. For living cells, further reduction of laser power was necessary, part of which could be attained by the use of outer detector.

11.Key Words

(1)calcium ion、(2)calcium channels、(3)receptor-activated channels
(4)hereditary cerebellar ataxia、(5)Biosensor、(6)two-photon excitation laser microscopy
(7)phosophoinositol metabolism、(8)abnormal brain rhythm generation、(9)neural plasticity

12.References

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Okada T et al Molecular and functional characterization of a novel mouse transient receptor potential protein homologue TRP7: Ca2+-permeable cation channel that is constitutively activated and enhanced by stimulation of G protein-coupled receptor
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Yamada H et al Spontaneous single-channel activity of neuronal TRP5 channel recombinantly expressed in HEK293 cells
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Mori Y et al Reduced voltage sensitivity of activation of P/Q-type Ca2+ channels is associated with the ataxic mouse mutation rolling nagoya
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