Induction and maintenance mechanism of late phase of cerebellar synaptic plasticity

小脑突触可塑性后期的诱导和维持机制

• 批准号: 12480238
• 负责人: HIRANO Tomoo
• 金额: $ 9.34万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12480238/
• 关键词: Cerebellum; Purkinje cell; Synaptic plasticity; Glutamate; GABA; miniature postsynaptic current; Transcription; Calcineurin; プリキンエ細胞; 長期抑圧; 長期増強; mRNA合成; 培養; mEPSC; mIPSC

The synaptic plasticity in the cerebellum has been considered as a cellular basis of motor learning. Long-term depression (LTD) at excitatory synapses between a granule neuron and a Purkinje neuron and rebound potentiation (RP) at inhibitory synapses between an interneuron and a Purkinje neuron, has been reported. The synaptic plasticity is composed of transcription-independent early phase and transcription-dependent late phase. In this study, we have studied the expression and maintenance mechanism of late phase of synaptic plasticity utilizing measurement of miniature excitatory or inhibitory postsynaptic current (mEPSC, mIPSC) in the rat cerebellar culture. We found that inhibition of calcineurin (a calcium and calmodulin dependent protein phosphatase) induced the late phase of LTD. Our results suggest that down regulation of calcineurin by superoxide triggers the induction of late phase of LTD in a Purkinje neuron. We also succeeded to demonstrate whole time course of RP. RP also consisted of early phase and transcription-dependent late phase lasting for more than a day.

小脑的突触可塑性被认为是运动学习的细胞基础。颗粒神经元和浦肯野神经元之间的兴奋性突触处的长时程抑制（LTD）和中间神经元和浦肯野神经元之间的抑制性突触处的反弹增强（RP）已被报道。突触可塑性由转录非依赖的早期和转录依赖的晚期组成。本研究采用大鼠小脑培养细胞，通过测量微小兴奋性或抑制性突触后电流（mEPSC，mIPSC），研究了突触可塑性晚期的表达和维持机制。我们发现，钙调磷酸酶（钙和钙调蛋白依赖性蛋白磷酸酶）的抑制诱导的LTD.Our研究结果表明，钙调磷酸酶的超氧化物的下调触发了浦肯野神经元中的LTD的晚期相的诱导。我们还成功地演示了RP的全时程。RP也包括早期阶段和转录依赖的晚期阶段持续超过一天。

项目成果

Fujii, H., Hirano, T.: "Calcineurin regulates induction of late phase of cerebellar long-term depression in rat cultured Purkinje neurons"European Journal of Neuroscience. 16. 1777-1788 (2002)

Fujii, H., Hirano, T.：“钙调神经磷酸酶调节大鼠培养的浦肯野神经元小脑长期抑郁晚期的诱导”《欧洲神经科学杂志》。

Kawaguchi, S., Hirano, T.: "Suppression of inhibitory synaptic potentiation by presynaptic activity through postsynaptic GABA_B receptors in a Purkinje neuron"Neuron. 27. 339-347 (2000)

Kawaguchi, S., Hirano, T.：“通过浦肯野神经元中的突触后 GABA_B 受体通过突触前活动抑制抑制性突触增强”Neuron。

Hirano, T. et al.: "Roles of inhibitory interneurons in the cerebellar cortex"Annals of New York Academy of Science. 978. 405-412 (2002)

Hirano, T. 等人：“小脑皮质中抑制性中间神经元的作用”纽约科学院年鉴。

Yamasaki, T.: "Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum"Development. 128. 3133-3144 (2001)

Yamasaki, T.：“Pax6 在发育中小脑平行纤维形成过程中调节颗粒细胞极化”开发。

Kawaguchi, S. Hirano, T.: "Signaling cascade regulating long-term potentiation of GABA_A receptor responsiveness in cerebellar Purkinje neurons"Journal of Neuroscience. 22. 3969-3976 (2002)

Kawaguchi, S. Hirano, T.：“信号级联调节小脑浦肯野神经元中 GABA_A 受体反应性的长期增强”神经科学杂志。