Xue Weikang, Chen Yuanhua, Lei Ziyi, Wang Yuanxia, Liu Jiaze, Wen Xin, Xu Fang, Chen Pu, Wu Zhengxing, Jin Youngnam N, Yu Yanxun V
Department of Neurology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
College of Life Science, Henan Agricultural University, Zhengzhou, China.
Nat Commun. 2025 Feb 20;16(1):1814. doi: 10.1038/s41467-025-57051-x.
The valence of stimuli is shaped by various factors, including environmental cues, internal states, genetic variability, and past experience. However, the mechanisms behind this flexibility remain elusive. In the nematode C. elegans, we found that ethanol, an olfactory stimulus, can elicit opposite chemotaxis responses - attraction vs. aversion - depending on NaCl concentration, demonstrating the role of environmental factors in altering valence. Remarkably, a single chemosensory neuron, ASER, orchestrate this bidirectional ethanol chemotaxis by integrating information from both stimuli - ethanol and NaCl - into its neuronal activity dynamics. Specifically, different calcium dynamics in the ASER neuron differentially activate the signaling molecule CMK-1, thereby engaging different downstream interneurons and leading to opposite chemotaxis directions. Consistently, optogenetic manipulations of the ASER neuron reverse the chemotaxis directions, by altering its calcium dynamics. Our findings reveal a mechanism by which a single neuron integrates multisensory inputs to determine context-dependent behavioral valence, contributing to our current understanding of valence encoding.
刺激的效价受多种因素影响，包括环境线索、内部状态、基因变异性和过去的经验。然而，这种灵活性背后的机制仍然难以捉摸。在秀丽隐杆线虫中，我们发现乙醇这种嗅觉刺激，根据氯化钠浓度的不同，能引发相反的趋化反应——吸引与厌恶，这表明环境因素在改变效价方面的作用。值得注意的是，单个化学感觉神经元ASER通过将来自乙醇和氯化钠这两种刺激的信息整合到其神经元活动动态中，来协调这种双向乙醇趋化作用。具体而言，ASER神经元中不同的钙动态差异激活信号分子CMK-1，从而与不同的下游中间神经元相互作用，导致相反的趋化方向。同样，通过改变其钙动态，对ASER神经元进行光遗传学操作会逆转趋化方向。我们的研究结果揭示了一种机制，即单个神经元整合多感官输入以确定依赖于情境的行为效价，这有助于我们目前对价态编码的理解。
