Four Individually Identified Paired Dopamine Neurons Signal Reward in Larval Drosophila
Four Individually Identified Paired Dopamine Neurons Signal Reward in Larval Drosophila
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DOI：
10.1016/j.cub.2016.01.012
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发表时间：
2016-03-07
期刊：
影响因子：
9.2
通讯作者：
Thum, Andreas S.
中科院分区：
文献类型：
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作者：
Rohwedder, Astrid;Wenz, Nana L.;Thum, Andreas S.
多巴胺能神经元具有多种功能，包括在联想学习过程中的强化处理[1-12]。因此，有必要了解哪些多巴胺能神经元介导哪些功能。我们研究了果蝇幼虫，其中总共10，000个神经元中只有大约120个是多巴胺能的，这是通过酪氨酸羟化酶（TH）（多巴胺生物合成的限速酶）的表达来判断的[5，13]。介导昆虫嗅觉学习强化的多巴胺能神经元靶向蘑菇体，这是一个高阶“皮质”脑区[1-5，11，12，14，15]。我们发现了四个以前未描述的配对神经元，原脑前内侧（pPAM）神经元。这些神经元是TH阳性的，并将蘑菇体的内侧叶细分为四个不同的亚单位。这些pPAM神经元对于气味-糖奖励学习是非常必要的，并且在这个过程中需要完整的TH功能。然而，他们对气味和糖的厌恶性学习和先天行为是有害的。pPAM神经元的光遗传激活足以作为奖励。因此，pPAM神经元传递可能的多巴胺能奖励信号。相比之下，DL 1簇神经元传达相应的惩罚信号[5]，表明细胞分工传达多巴胺能奖励和惩罚信号。在单独识别的神经元的水平上，这揭示了与成年果蝇和哺乳动物共有的组织原则[1-4，7，9，10]（但参见[6]）。幼虫神经系统[16-19]的数值简单性和连接组学的易处理性现在为以前所未有的分辨率研究多巴胺功能的电路原理提供了前景。
Dopaminergic neurons serve multiple functions, including reinforcement processing during associative learning [1-12]. It is thus warranted to understand which dopaminergic neurons mediate which function. We study larval Drosophila, in which only approximately 120 of a total of 10,000 neurons are dopaminergic, as judged by the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine biosynthesis [5, 13]. Dopaminergic neurons mediating reinforcement in insect olfactory learning target the mushroom bodies, a higher-order "cortical'' brain region [1-5, 11, 12, 14, 15]. We discover four previously undescribed paired neurons, the primary protocerebral anterior medial (pPAM) neurons. These neurons are TH positive and subdivide the medial lobe of the mushroom body into four distinct subunits. These pPAM neurons are acutely necessary for odor-sugar reward learning and require intact TH function in this process. However, they are dispensable for aversive learning and innate behavior toward the odors and sugars employed. Optogenetical activation of pPAM neurons is sufficient as a reward. Thus, the pPAM neurons convey a likely dopaminergic reward signal. In contrast, DL1 cluster neurons convey a corresponding punishment signal [5], suggesting a cellular division of labor to convey dopaminergic reward and punishment signals. On the level of individually identified neurons, this uncovers an organizational principle shared with adult Drosophila and mammals [1-4, 7, 9, 10] (but see [6]). The numerical simplicity and connectomic tractability of the larval nervous system [16-19] now offers a prospect for studying circuit principles of dopamine function at unprecedented resolution.