ASI regulates satiety quiescence in C. elegans.
ASI regulates satiety quiescence in C. elegans.
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DOI：
10.1523/jneurosci.4493-12.2013
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发表时间：
2013-06-05
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影响因子：
--
通讯作者：
You YJ
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作者：
Gallagher T;Kim J;Oldenbroek M;Kerr R;You YJ
In C.在哺乳动物中，饱腹感静止模仿饱腹感和餐后睡眠的行为方面。在钙离子成像、遗传学和行为学研究的基础上，我们报道了一对两栖类神经元ASI被营养激活，并调节蠕虫的行为状态，特别是促进饱腹-静止; ASI抑制蠕虫从静止到栖居（一种浏览状态）的转换，并加速蠕虫从栖居到静止的转换。经典的TGFβ途径，其配体从ASI释放，调节饱腹感静止。TGFβ通路中的配体、受体和SMAD的突变体都比野生型吃得更多，并且表现出更少的静止。下游神经元RIM和RIC中的TGFβ受体足以使蠕虫表现出饱腹感静止，这表明从ASI到RIM和RIC的神经元连接对于通过TGFβ途径进行摄食调节是必不可少的。ASI还部分通过cGMP信号调节饱腹感静止;在ASI中恢复cGMP信号挽救cGMP信号突变体的饱腹感静止缺陷。根据这些结果，我们认为ASI中的TGFβ和cGMP通路将营养状况与促进饱腹感静止（一种睡眠样行为状态）联系起来。
In C. elegans, satiety quiescence mimics behavioral aspects of satiety and post-prandial sleep in mammals. On the basis of calcium-imaging, genetics and behavioral studies, here we report that a pair of amphid neurons ASI is activated by nutrition and regulates worms’ behavioral states specifically promoting satiety quiescence; ASI inhibits the switch from quiescence to dwelling (a browsing state) and accelerates the switch from dwelling to quiescence. The canonical TGFβ pathway, whose ligand is released from ASI, regulates satiety quiescence. The mutants of a ligand, a receptor and SMADs in the TGFβ pathway all eat more and show less quiescence than wild type. The TGFβ receptor in downstream neurons RIM and RIC is sufficient for worms to exhibit satiety quiescence, suggesting neuronal connection from ASI to RIM and RIC is essential for feeding regulation through the TGFβ pathway. ASI also regulates satiety quiescence partly through cGMP signaling; restoring cGMP signaling in ASI rescues the satiety quiescence defect of cGMP signaling mutants. From these results, we propose that TGFβ and cGMP pathways in ASI connect nutritional status to promotion of satiety quiescence, a sleep-like behavioral state.