1999 Fiscal Year Final Research Report Summary
Functional analysis of the glutamate receptor δ2 subunit in the motor learning
| Project/Area Number |
10680716
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MORI Hisashi The University of Tokyo, Graduate School of Medicine Lecturer, 大学院・医学系研究科, 講師 (00239617)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Glutamate receptor / GluRδ2 subunit / Motor learning / Eye blink conditioning / Cerebellar Purkinje cells / Cerebellar granule cells / Cre recombinase |
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| Research Abstract |
Glutamate receptor (GluR) channels mediate most of fast excitatory synaptic transmission in the vertebrate central nervous system. The GluRδ2 subunit expressed specifically in cerebellar Purkinje cells, and it's ablation resulted in impairements of long term depression (LTD), motor coordination, and refinement of synapses. GluRδ2 deficient mice received classical eyeblink conditioning. In the delay paradigm in which the conditioned stimuluus (CS) overlapped temporally with unconditioned stimulus (US). GluRδ2 mutant mice exhibited a severe impairment in learning. However, in the trace paradigm in which a stimulus-free trace interval intervened between the CS and US. GluRδ2 mutant mice learned as successfully as wild-type mice. Therefore, cerebellar LTD is essential in the delay paradigm, but not in the trace paradigm, suggesting an alteration of cerebellar neural substrates underlying eyeblink conditioning depending on the temporal overlap of the CS and US. Furthermore, to develop a cell type-specific and temporal regulation system of gene targeting in the cerebellum, we employed the NMDA receptor GluRε3 subunit gene and Cre recombinase-progesterone receptor fusion (CrePR) gene in combination. We established a ECP25 transgenic mouse line that strongly expressed the CrePR mRNA selectively in the granule cells of the cerebellum. We showed that antiprogestins could induce the recombinase activity of CrePR fusion protein of ECP25 mouse in the cerebellar granule cells. Thus, the established mouse line will provide a valuable tool to investigate the mechanism of cerebellar function by manipulating molecules in the temporally regulated and granule cell-specific manner.
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Research Products
(8 results)
