Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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Research Abstract |
The cerebellum has an essential role in motor coordination and motor learning. To investigate the neural circuit underlying motor learning and the retention of motor memory, we developed a genetic cell-ablation system in the mouse. In this mouse, ligand-induced recombination results in preferential ablation of Purkinje cells. Along with the Purkinje cell loss, these mice exhibited dystonic movement of the feet, severe ataxia, and ligand-dependent impaired performance in the rotarod test. Eyeblink conditioning was analyzed to further address the role of Purkinje cells in motor learning and the expression of motor memory. In a delay paradigm (cerebellum-dependent associative learning), administration of ligand impaired acquisition of the conditioned response and expression of the acquired conditioned response. In a trace paradigm (hippocampus-dependent associative learning), the acquired conditioned response was also impaired after ligand administration. There was no obvious anatomic abnormality of the ponto-cerebellar pathway in ligand-administered mice. Furthermore, the mice had normal responses to aversive stimuli. These results suggest that Purkinje cells have a crucial role in cerebellar-dependent motor learning, the expression of motor memory, and in the performance of hippocampal-dependent associative motor memory.
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