A Single Dopamine Pathway Underlies Progressive Locomotor Deficits in a Drosophila Model of Parkinson Disease
A Single Dopamine Pathway Underlies Progressive Locomotor Deficits in a Drosophila Model of Parkinson Disease
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DOI：
10.1016/j.celrep.2013.10.032
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发表时间：
2013-11-01
期刊：
影响因子：
8.8
通讯作者：
Birman, Serge
中科院分区：
文献类型：
--
作者：
Riemensperger, Thomas;Issa, Abdul-Raouf;Birman, Serge
人类帕金森病相关蛋白α-突触核蛋白在所有果蝇神经元中的表达会诱导进行性运动缺陷。在这里，我们在大脑前内侧区域的每个半球确定了一组 15 个多巴胺能神经元，其破坏与该模型中的攀爬障碍相关。这些神经元选择性地支配蘑菇体的水平 β 和 β' 叶，当它们表达 α-突触核蛋白时，它们与凯尼恩细胞的连接显着减少。使用选择性蘑菇体驱动器，我们发现阻断或过度刺激β'叶中的神经元活动，而不是β或γ叶中的神经元活动，可以显着抑制负趋地性行为。这表明，通过这种多巴胺能途径调节蘑菇体β'叶对于有效控制果蝇惊吓引起的运动是特别需要的。
Expression of the human Parkinson-disease-associated protein alpha-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal beta and beta' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express alpha-synuclein. Using selective mushroom body drivers, we show that blocking or overstimulating neuronal activity in the beta' lobe, but not the beta or gamma lobes, significantly inhibits negative geotaxis behavior. This suggests that modulation of the mushroom body beta' lobes by this dopaminergic pathway is specifically required for an efficient control of startle-induced locomotion in flies.