Chang Andy J, Chronis Nikolas, Karow David S, Marletta Michael A, Bargmann Cornelia I
Howard Hughes Medical Institute and Laboratory of Neural Circuits and Behavior, The Rockefeller University, New York, New York, United States of America.
PLoS Biol. 2006 Sep;4(9):e274. doi: 10.1371/journal.pbio.0040274.
The nematode Caenorhabditis elegans has complex, naturally variable behavioral responses to environmental oxygen, food, and other animals. C. elegans detects oxygen through soluble guanylate cyclase homologs (sGCs) and responds to it differently depending on the activity of the neuropeptide receptor NPR-1: npr-1(lf) and naturally isolated npr-1(215F) animals avoid high oxygen and aggregate in the presence of food; npr-1(215V) animals do not. We show here that hyperoxia avoidance integrates food with npr-1 activity through neuromodulation of a distributed oxygen-sensing network. Hyperoxia avoidance is stimulated by sGC-expressing oxygen-sensing neurons, nociceptive neurons, and ADF sensory neurons. In npr-1(215V) animals, the switch from weak aerotaxis on food to strong aerotaxis in its absence requires close regulation of the neurotransmitter serotonin in the ADF neurons; high levels of ADF serotonin promote hyperoxia avoidance. In npr-1(lf) animals, food regulation is masked by increased activity of the oxygen-sensing neurons. Hyperoxia avoidance is also regulated by the neuronal TGF-beta homolog DAF-7, a secreted mediator of crowding and stress responses. DAF-7 inhibits serotonin synthesis in ADF, suggesting that ADF serotonin is a convergence point for regulation of hyperoxia avoidance. Coalitions of neurons that promote and repress hyperoxia avoidance generate a subtle and flexible response to environmental oxygen.
线虫秀丽隐杆线虫对环境中的氧气、食物和其他动物具有复杂的、自然可变的行为反应。秀丽隐杆线虫通过可溶性鸟苷酸环化酶同源物（sGCs）检测氧气，并根据神经肽受体NPR-1的活性做出不同反应：npr-1(lf)和自然分离的npr-1(215F)动物避免高氧并在有食物时聚集；npr-1(215V)动物则不会。我们在此表明，高氧回避通过对分布式氧传感网络的神经调节将食物与npr-1活性整合在一起。高氧回避受到表达sGC的氧传感神经元、伤害感受神经元和ADF感觉神经元的刺激。在npr-1(215V)动物中，从在食物上的弱趋氧性转变为在无食物时的强趋氧性需要密切调节ADF神经元中的神经递质5-羟色胺；高水平的ADF 5-羟色胺促进高氧回避。在npr-1(lf)动物中，食物调节被氧传感神经元活性增加所掩盖。高氧回避也受到神经元TGF-β同源物DAF-7的调节，DAF-7是拥挤和应激反应的分泌介质。DAF-7抑制ADF中的5-羟色胺合成，表明ADF 5-羟色胺是高氧回避调节的汇聚点。促进和抑制高氧回避的神经元联盟对环境氧气产生微妙而灵活的反应。
