Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
J Neurosci. 2013 Jun 5;33(23):9716-24. doi: 10.1523/JNEUROSCI.4493-12.2013.
In Caenorhabditis elegans, satiety quiescence mimics behavioral aspects of satiety and postprandial 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.
在秀丽隐杆线虫中，饱腹感静止模拟了哺乳动物饱腹感和餐后睡眠的行为方面。基于钙成像、遗传学和行为研究，我们在这里报告说，一对触角神经元 ASI 被营养激活，并专门调节蠕虫的行为状态，促进饱腹感静止；ASI 抑制从静止到居住（浏览状态）的转变，并加速从居住到静止的转变。经典的 TGFβ 途径，其配体从 ASI 释放，调节饱腹感静止。TGFβ 途径中的配体、受体和 SMADs 的突变体比野生型吃得更多，表现出的静止状态更少。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 途径进行进食调节是必不可少的。ASI 还通过 cGMP 信号部分调节饱腹感静止；在 ASI 中恢复 cGMP 信号可挽救 cGMP 信号突变体的饱腹感静止缺陷。根据这些结果，我们提出 ASI 中的 TGFβ 和 cGMP 途径将营养状况与促进饱腹感静止（类似睡眠的行为状态）联系起来。
