Zhang Mark G, Seyedolmohadesin Maedeh, Hawk Soraya, Park Heenam, Finnen Nerissa, Schroeder Frank, Venkatachalam Vivek, Sternberg Paul W
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Physics Department, Northeastern University, Boston, MA, USA.
bioRxiv. 2024 Mar 25:2024.03.20.586022. doi: 10.1101/2024.03.20.586022.
Decisions made over long time scales, such as life cycle decisions, require coordinated interplay between sensory perception and sustained gene expression. The dauer (or diapause) exit developmental decision requires sensory integration of population density and food availability to induce an all-or-nothing organismal-wide response, but the mechanism by which this occurs remains unknown. Here, we demonstrate how the ASJ chemosensory neurons, known to be critical for dauer exit, perform sensory integration at both the levels of gene expression and calcium activity. In response to favorable conditions, dauers rapidly produce and secrete the dauer exit-promoting insulin-like peptide INS-6. Expression of in the ASJ neurons integrate population density and food level and can reflect decision commitment since dauers committed to exiting have higher expression levels than those of non-committed dauers. Calcium imaging in dauers reveals that the ASJ neurons are activated by food, and this activity is suppressed by pheromone, indicating that sensory integration also occurs at the level of calcium transients. We find that expression in the ASJ neurons depends on neuronal activity in the ASJs, cGMP signaling, a CaM-kinase pathway, and the pheromone components ascr#8 and ascr#2. We propose a model in which decision commitment to exit the dauer state involves an autoregulatory feedback loop in the ASJ neurons that promotes high INS-6 production and secretion. These results collectively demonstrate how insulin-like peptide signaling helps animals compute long-term decisions by bridging sensory perception to decision execution.
在较长时间尺度上做出的决策,如生命周期决策,需要感官感知与持续的基因表达之间进行协调相互作用。滞育(或滞育)解除发育决策需要对种群密度和食物可利用性进行感官整合,以引发一种全或无的全身性反应,但其发生机制尚不清楚。在这里,我们展示了已知对滞育解除至关重要的ASJ化学感受神经元如何在基因表达和钙活性水平上进行感官整合。在有利条件下,滞育个体迅速产生并分泌促进滞育解除的胰岛素样肽INS-6。ASJ神经元中的 表达整合了种群密度和食物水平,并且可以反映决策承诺,因为决定解除滞育的滞育个体比未决定的滞育个体具有更高的 表达水平。对滞育个体进行钙成像显示,ASJ神经元被食物激活,并且这种活性被信息素抑制,这表明在钙瞬变水平上也发生了感官整合。我们发现ASJ神经元中的 表达取决于ASJ中的神经元活性、cGMP信号传导、一条钙调蛋白激酶途径以及信息素成分ascr#8和ascr#2。我们提出了一个模型,其中决定退出滞育状态的决策承诺涉及ASJ神经元中的一个自动调节反馈回路,该回路促进INS-6的高产量和分泌。这些结果共同证明了胰岛素样肽信号传导如何通过将感官感知与决策执行联系起来,帮助动物做出长期决策。