对于小鼠的基本运动行为来说,Synaptotagmin-1-依赖相位轴突的多巴胺释放是不可或缺的
Benoît Delignat-Lavaud1,2,3, Jana Kano1,2,3, Charles Ducrot1,2,3
1Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
Nature communications
|July 11, 2023
概括
帕金森病的运动功能保持完整,即使多巴胺 (DA) 释放严重受损. 这表明基底DA水平,而不是活动依赖释放,维持运动行为.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 生理学 生理学 生理学
背景情况:
- 帕金森病 (PD) 的运动症状出现较晚,这表明多巴胺 (DA) 损失的补偿机制.
- 基础DA音调与活动依赖的DA释放在运动控制中的作用尚未完全理解.
研究的目的:
- 调查活动依赖DA释放对于运动行为的必要性.
- 探索基础DA音调在相位DA释放受损时的补偿作用.
主要方法:
- 在DA神经元中 (Syt1 cKO DA小鼠) 条件删除协同胺-1 (Syt1),以消除轴突DA释放.
- 在Syt1 cKODA小鼠中评估运动任务性能和动机.
- 在状体中测量基底细胞外DA水平.
主要成果:
- Syt1 cKODA小鼠表现出取消了活动依赖的轴突DA释放,但完整的体膜释放.
- 在Syt1 cKODA小鼠中,运动任务性能和有条件的动机没有受到影响.
- 状体中的基底细胞外DA水平没有变化.
结论:
- 活动依赖的DA释放对于无条件的运动任务和动机是不可或缺的.
- 基础DA音调足以维持运动功能,尽管相位DA释放几乎被废除了.
- 这种弹性解释了为什么在PD中广泛的DA神经元损失会先于运动缺陷.
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