Dopamine receptor DOP-4 modulates habituation to repetitive photoactivation of a C. elegans polymodal nociceptor.

Dopamine receptor DOP-4 modulates habituation to repetitive photoactivation of a C. elegans polymodal nociceptor.
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DOI:
10.1101/lm.041830.116
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发表时间:
2016-10
期刊:
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子:
--
通讯作者:
Rankin CH
Rankin CH
中科院分区:
其他
文献类型:
--
作者:
Ardiel EL;Giles AC;Yu AJ;Lindsay TH;Lockery SR;Rankin CH

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习惯化是一种高度保守的现象,在分子水平上仍然知之甚少。无脊椎动物模型系统,如秀丽隐杆线虫,可以成为研究这一基本过程的有力工具。在这里,我们建立了一种高通量学习测试,它使用实时计算机视觉软件进行行为跟踪和光遗传学刺激线虫多模式伤害性感受器ASH。用ChR2光激活ASH引起后向运动,重复刺激以与习惯化一致的方式改变了反应的各个方面。在ASH中记录光电流,我们没有观察到ChR2对光适应的证据。此外,我们通过证明来自触摸细胞的感觉输入可以破坏ASH避免电路,从而排除了疲劳的可能性。食物和多巴胺信号通过D1样多巴胺受体DOP-4减缓ASH刺激下游的习服。这种分析方法可以进行大规模的遗传和药物筛选,研究伤害性感受的调节机制。
Habituation is a highly conserved phenomenon that remains poorly understood at the molecular level. Invertebrate model systems, like Caenorhabditis elegans, can be a powerful tool for investigating this fundamental process. Here we established a high-throughput learning assay that used real-time computer vision software for behavioral tracking and optogenetics for stimulation of the C. elegans polymodal nociceptor, ASH. Photoactivation of ASH with ChR2 elicited backward locomotion and repetitive stimulation altered aspects of the response in a manner consistent with habituation. Recording photocurrents in ASH, we observed no evidence for light adaptation of ChR2. Furthermore, we ruled out fatigue by demonstrating that sensory input from the touch cells could dishabituate the ASH avoidance circuit. Food and dopamine signaling slowed habituation downstream from ASH excitation via D1-like dopamine receptor, DOP-4. This assay allows for large-scale genetic and drug screens investigating mechanisms of nociception modulation.
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