Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, 162-8666, Japan.
Sci Rep. 2022 Feb 3;12(1):1907. doi: 10.1038/s41598-022-05942-0.
The central neural network optimizes avoidance behavior depending on the nociceptive stimulation intensity and is essential for survival. How the property of hub neurons that enables the selection of behaviors is genetically defined is not well understood. We show that the transcription factor unc-130, a human FOXD3/4 ortholog, is required to optimize avoidance behavior depending on stimulus strength in Caenorhabditis elegans. unc-130 is necessary for both ON responses (calcium decreases) and OFF responses (calcium increases) in AIBs, central neurons of avoidance optimization. Ablation of predicted upstream inhibitory neurons reduces the frequency of turn behavior, suggesting that optimization needs both calcium responses. At the molecular level, unc-130 upregulates the expression of at least three genes: nca-2, a homolog of the vertebrate cation leak channel NALCN; glr-1, an AMPA-type glutamate receptor; and eat-4, a hypothetical L-glutamate transmembrane transporter in the central neurons of optimization. unc-130 shows more limited regulation in optimizing behavior than an atonal homolog lin-32, and unc-130 and lin-32 appear to act in parallel molecular pathways. Our findings suggest that unc-130 is required for the establishment of some AIB identities to optimize avoidance behavior.
中枢神经网络根据伤害性刺激强度优化回避行为，这对生存至关重要。中枢神经元的哪些特性使它们能够选择行为，其遗传定义还不太清楚。我们发现，转录因子 unc-130（人类 FOXD3/4 同源物）是秀丽隐杆线虫回避优化中中央神经元 AIB 中根据刺激强度优化回避行为所必需的。unc-130 对于 AIB 的 ON 反应（钙减少）和 OFF 反应（钙增加）都是必需的。预测的上游抑制性神经元的缺失会降低转弯行为的频率，这表明优化需要钙反应。在分子水平上，unc-130 上调了至少三种基因的表达：nca-2，一种脊椎动物阳离子泄漏通道 NALCN 的同源物；glr-1，一种 AMPA 型谷氨酸受体；以及 eat-4，优化中央神经元中的一种假设的 L-谷氨酸跨膜转运蛋白。unc-130 在优化行为中的调节作用比其同源物 lin-32 更为有限，而且 unc-130 和 lin-32 似乎在平行的分子途径中发挥作用。我们的研究结果表明，unc-130 是建立某些 AIB 身份以优化回避行为所必需的。
