Dissection of the Drosophila neuropeptide F circuit using a high-throughput two-choice assay

Dissection of the Drosophila neuropeptide F circuit using a high-throughput two-choice assay
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DOI:
10.1073/pnas.1710552114
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发表时间:
2017-09-19
影响因子:
11.1
通讯作者:
Heberlein, Ulrike
Heberlein, Ulrike
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Shao, Lisha;Saver, Mathias;Heberlein, Ulrike

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在他们的经典实验中,奥尔兹和米尔纳表明,老鼠学会了在特定的大脑区域接受电刺激。这导致了哺乳动物奖励中心的识别。我们对定义果蝇(Drosophila melanogaster)奖励感知的神经元底物的兴趣促使我们开发了一种更简单的实验方法,其中苍蝇可以实施诱导其大脑中特定神经元自我刺激的行为。当果蝇占据行为室的特定区域时,高通量测定采用神经元的光遗传学激活,并且果蝇优先占据该区域反映了它们选择经历光遗传学刺激。其中神经肽F(NPF)神经元被激活的苍蝇显示对室的照明侧的偏好。我们发现,光遗传学激活的NPF神经元是奖励的嗅觉条件反射实验和NPF神经元激活的偏好是依赖于NPF信号。最后,我们确定了一个小的NPF表达神经元位于背内侧后脑,足以引起我们的测定偏好的子集。该测定提供了用于进行无偏筛选以映射果蝇中的奖励神经元的手段。
In their classic experiments, Olds and Milner showed that rats learn to lever press to receive an electric stimulus in specific brain regions. This led to the identification of mammalian reward centers. Our interest in defining the neuronal substrates of reward perception in the fruit fly Drosophila melanogaster prompted us to develop a simpler experimental approach wherein flies could implement behavior that induces self-stimulation of specific neurons in their brains. The high-throughput assay employs optogenetic activation of neurons when the fly occupies a specific area of a behavioral chamber, and the flies' preferential occupation of this area reflects their choosing to experience optogenetic stimulation. Flies in which neuropeptide F (NPF) neurons are activated display preference for the illuminated side of the chamber. We show that optogenetic activation of NPF neuron is rewarding in olfactory conditioning experiments and that the preference for NPF neuron activation is dependent on NPF signaling. Finally, we identify a small subset of NPF-expressing neurons located in the dorsomedial posterior brain that are sufficient to elicit preference in our assay. This assay provides the means for carrying out unbiased screens to map reward neurons in flies.