Dissection of a sensorimotor circuit underlying pathogen aversion in C. elegans.

Dissection of a sensorimotor circuit underlying pathogen aversion in C. elegans.
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DOI:
10.1186/s12915-022-01424-x
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发表时间:
2022-10-08
期刊:
影响因子:
5.4
通讯作者:
Aballay, Alejandro
Aballay, Alejandro
中科院分区:
生物学2区
文献类型:
--
作者:
Filipowicz, Adam;Lalsiamthara, Jonathan;Aballay, Alejandro

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改变动物行为以减少病原体暴露是抵御病原体攻击的关键防线。在秀丽隐杆线虫中,病原体定殖和微生物代谢产物的感觉引起的肠道生理变化可能会导致病原体厌恶行为的激活,从厌恶反射到习得性回避。然而,化学感觉神经元之间的神经回路,感觉致病细菌的线索和运动神经元负责回避相关的运动仍然是未知的。利用C.在elegans中,我们发现向后运动是习得性病原体回避的一个组成部分,因为预先暴露于铜绿假单胞菌或粪肠球菌的动物显示出对由化学感觉神经元(包括嗅觉AWB神经元)驱动的细菌滴的反射性厌恶。这种反应也涉及肠扩张,对于E。粪肠球菌,需要在肠道和排泄系统中表达TRPM通道。此外,我们还发现了一个由嗅觉神经元、中间神经元和运动神经元组成的回路,它控制着向后运动,这对学习性反射性厌恶致病细菌、学习性回避和令人厌恶的气味2-壬酮至关重要。使用全脑模拟和功能分析,我们发现了一种新的感觉运动回路控制学习反射性厌恶。发现一个完整的感觉运动回路反射性厌恶证明了使用C。elegans连接组和计算建模在揭示新的神经元调节行为。在线版本包含补充材料,可通过10.1186/s12915-022-01424-x获得。
Altering animal behavior to reduce pathogen exposure is a key line of defense against pathogen attack. In Caenorhabditis elegans, alterations in intestinal physiology caused by pathogen colonization and sensation of microbial metabolites may lead to activation of pathogen aversive behaviors ranging from aversive reflexes to learned avoidance. However, the neural circuitry between chemosensory neurons that sense pathogenic bacterial cues and the motor neurons responsible for avoidance-associated locomotion remains unknown. Using C. elegans, we found that backward locomotion was a component of learned pathogen avoidance, as animals pre-exposed to Pseudomonas aeruginosa or Enterococcus faecalis showed reflexive aversion to drops of the bacteria driven by chemosensory neurons, including the olfactory AWB neurons. This response also involved intestinal distention and, for E. faecalis, required expression of TRPM channels in the intestine and excretory system. Additionally, we uncovered a circuit composed of olfactory neurons, interneurons, and motor neurons that controls the backward locomotion crucial for learned reflexive aversion to pathogenic bacteria, learned avoidance, and the repulsive odor 2-nonanone. Using whole-brain simulation and functional assays, we uncovered a novel sensorimotor circuit governing learned reflexive aversion. The discovery of a complete sensorimotor circuit for reflexive aversion demonstrates the utility of using the C. elegans connectome and computational modeling in uncovering new neuronal regulators of behavior. The online version contains supplementary material available at 10.1186/s12915-022-01424-x.
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