Shyn Stanley I, Kerr Rex, Schafer William R
Program in Neurosciences, University of California, San Diego, La Jolla 92093, USA.
Curr Biol. 2003 Oct 28;13(21):1910-5. doi: 10.1016/j.cub.2003.10.025.
From nematodes to humans, animals employ neuromodulators like serotonin to regulate behavioral patterns and states. In the nematode C. elegans, serotonin has been shown to act in a modulatory fashion to increase the rate and alter the temporal pattern of egg laying. Though many candidate effectors and regulators of serotonin have been identified in genetic studies, their effects on specific neurons and muscles in the egg-laying circuitry have been difficult to determine. Using the genetically encoded Ca(2+) indicator cameleon, we found that serotonin acts directly on the vulval muscles to increase the frequency of Ca(2+) transients. In contrast, we found that the spontaneous activity of the egg-laying motorneurons was silenced by serotonin. Mutations in G protein alpha subunit genes altered the responses of both vulval muscles and egg-laying neurons to serotonin; specifically, mutations in the G(q)alpha homolog egl-30 blocked serotonin stimulation of vulval muscle Ca(2+) transients, while mutations in the G(o)alpha homolog goa-1 prevented the silencing of motorneuron activity by serotonin. These data indicate that serotonin stimulates egg laying by directly modulating the functional state of the vulval muscles. In addition, serotonin inhibits the activity of the motorneurons that release it, providing a feedback regulatory effect that may contribute to serotonin adaptation.
从线虫到人类,动物都利用血清素等神经调质来调节行为模式和状态。在线虫秀丽隐杆线虫中,血清素已被证明以调节方式发挥作用,可提高产卵速率并改变产卵的时间模式。尽管在基因研究中已鉴定出许多血清素的候选效应器和调节因子,但它们对产卵神经回路中特定神经元和肌肉的影响却难以确定。利用基因编码的钙离子指示剂cameleon,我们发现血清素直接作用于外阴肌肉,以增加钙离子瞬变的频率。相比之下,我们发现血清素可使产卵运动神经元的自发活动沉默。G蛋白α亚基基因的突变改变了外阴肌肉和产卵神经元对血清素的反应;具体而言,G(q)α同源物egl-30中的突变阻断了血清素对外阴肌肉钙离子瞬变的刺激,而G(o)α同源物goa-1中的突变则阻止了血清素对运动神经元活动的沉默作用。这些数据表明,血清素通过直接调节外阴肌肉的功能状态来刺激产卵。此外,血清素抑制释放它的运动神经元的活动,提供一种反馈调节作用,这可能有助于血清素的适应性调节。