Flip-Flop回路调节线虫行为示意图。(a) 相互拮抗的感觉信号输入调节进食行为的回路示意图，实线表示神经元之间直接连接，虚线表示间接连接。(b) 感觉信号调节进食的回路与Flip-Flop电路对比。
4月10日，国际著名杂志《自然-通讯》Nature Communications在线发表了中国科学院生物物理研究所徐涛课题组最新研究成果：感觉信号调控线虫进食行为的中枢翻转回路解析（Dissecting a central flip-flop circuit that integrates contradictory sensory cues in C. elegans feeding regulation）。该研究在秀丽隐杆线虫（Caenorhabditis elegans）中发现了一种新的调控线虫抉择行为的神经回路模式。
当面临两难局面时，人或高等动物能权衡利弊，做出最有利的选择。在这个过程中，中枢神经系统整合不同甚至完全相反的感觉输入信号，决定生物个体行为抉择。感觉输入信号的整合对生物的生存至关重要，但其背后的分子机制如何仍不清楚。
线虫具有神经系统的组成相对简单（共118类302个神经元）和遗传操作便捷的优势，徐涛课题组发现，线虫可以用来研究相互拮抗的感觉输入是如何最终影响个体行为抉择的。他们采用两种化学物质——双乙酰酮和奎宁来同时刺激线虫。这两种物质分别通过线虫的嗅觉和味觉通路输入，对线虫进食行为的影响恰好相反：双乙酰酮增加进食，奎宁抑制进食。
结合遗传学方法及活体钙成像技术，研究证实，两路跨模态的感觉输入的整合具有“胜者全得” （winner-takes-all）的特性，其产生的机制依赖线虫咽部神经元NSM和咽外神经元RIM/RIC组成的一个相互抑制的中枢神经回路来实现。研究人员进而鉴定了介导互相抑制的分子回路。这样一种中枢的整合机制非常类似电子线路中的翻转（flip-flop）电路，可以保证较强的输入信号得到放大而使微小的信号得到过滤，从而使线虫的行为输出具有稳定性。（生物谷Bioon.com）
doi:10.1038/ncomms1780
PMC:
PMID:
Dissecting a central flip-flop circuit that integrates contradictory sensory cues in C. elegans feeding regulation
Zhaoyu Li, Yidong Li, Yalan Yi, Wenming Huang, Song Yang, Weipin Niu, Li Zhang, Zijing Xu, Anlian Qu, Zhengxing Wu & Tao Xu
Feeding behaviour is modulated by both environmental cues and internal physiological states. Appetite is commonly boosted by the pleasant smell (or appearance) of food and destroyed by a bad taste. In reality, animals sense multiple environmental cues at the same time and it is not clear how these sensory inputs are integrated and a decision is made to regulate feeding behaviour accordingly. Here we show that feeding behaviour in Caenorhabditis elegans can be either facilitated by attractive odours or suppressed by repellents. By identifying mutants that are defective for sensory-mediated feeding regulation, we dissected a central flip-flop circuit that integrates two contradictory sensory inputs and generates bistable hormone output to regulate feeding behaviour. As feeding regulation is fundamental to animal survival, we speculate that the basic organizational logic identified here in C. elegans is likely convergent throughout different phyla.
