Department of Biology, University of Fribourg, 1700 Fribourg, Switzerland.
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh EH8 9XD, Scotland.
Cell Rep. 2020 Jan 14;30(2):397-408.e4. doi: 10.1016/j.celrep.2019.12.029.
Pain sensation and aversive behaviors entail the activation of nociceptor neurons, whose function is largely conserved across animals. The functional heterogeneity of nociceptors and ethical concerns are challenges for their study in mammalian models. Here, we investigate the function of a single type of genetically identified C. elegans thermonociceptor named FLP. Using calcium imaging in vivo, we demonstrate that FLP encodes thermal information in a tonic and graded manner over a wide thermal range spanning from noxious cold to noxious heat (8°C-36°C). This tonic-signaling mode allows FLP to trigger sustained behavioral changes necessary for escape behavior. Furthermore, we identify specific transient receptor potential, voltage-gated calcium, and sodium "leak" channels controlling sensory gain, thermal sensitivity, and signal kinetics, respectively, and show that the ryanodine receptor is required for long-lasting activation. Our work elucidates the task distribution among specific ion channels to achieve remarkable sensory properties in a tonic thermonociceptor in vivo.
痛觉和厌恶行为需要伤害感受器神经元的激活,其功能在动物中基本保持一致。伤害感受器的功能异质性和伦理问题是在哺乳动物模型中研究它们的挑战。在这里,我们研究了一种单一类型的、已被基因鉴定的秀丽隐杆线虫热敏伤害感受器,称为 FLP。我们通过在体钙成像实验证明,FLP 在从有害冷到有害热(8°C-36°C)的广泛温度范围内以紧张和分级的方式编码热信息。这种紧张信号模式使 FLP 能够引发持续的行为变化,这些变化对于逃避行为是必要的。此外,我们确定了特定的瞬时受体电位、电压门控钙和钠“泄漏”通道,分别控制感觉增益、热敏感性和信号动力学,并表明肌醇 1,4,5-三磷酸受体对于持久激活是必需的。我们的工作阐明了特定离子通道之间的任务分配,以在体内紧张热敏伤害感受器中实现显著的感觉特性。