Basnakova Adriana, Cheng Ruey-Kuang, Chia Joanne Shu Ming, D'Agostino Giuseppe, Tan Germaine Jia Hui, Langley Sarah R, Jesuthasan Suresh
School of Biological Sciences, University of Manchester, UK.
Institute of Molecular and Cell Biology, Singapore.
Neurobiol Stress. 2021 Sep 23;15:100403. doi: 10.1016/j.ynstr.2021.100403. eCollection 2021 Nov.
The response of an animal to a sensory stimulus depends on the nature of the stimulus and on expectations, which are mediated by spontaneous activity. Here, we ask how circadian variation in the expectation of danger, and thus the response to a potential threat, is controlled. We focus on the habenula, a mediator of threat response that functions by regulating neuromodulator release, and use zebrafish as the experimental system. Single cell transcriptomics indicates that multiple clock genes are expressed throughout the habenula, while quantitative in situ hybridization confirms that the clock oscillates. Two-photon calcium imaging indicates a circadian change in spontaneous activity of habenula neurons. To assess the role of this clock, a truncated gene was specifically expressed in the habenula. This partially inhibited the clock, as shown by changes in expression as well as altered day-night variation in dopamine, serotonin and acetylcholine levels. Behaviourally, anxiety-like responses evoked by an alarm pheromone were reduced. Circadian effects of the pheromone were disrupted, such that responses in the day resembled those at night. Behaviours that are regulated by the pineal clock and not triggered by stressors were unaffected. We suggest that the habenula clock regulates the expectation of danger, thus providing one mechanism for circadian change in the response to a stressor.
动物对感觉刺激的反应取决于刺激的性质以及由自发活动介导的预期。在此，我们探究对危险的预期中的昼夜节律变化以及对潜在威胁的反应是如何被控制的。我们聚焦于缰核，它是通过调节神经调质释放来发挥作用的威胁反应的介导者，并以斑马鱼作为实验系统。单细胞转录组学表明多个时钟基因在整个缰核中表达，而定量原位杂交证实了生物钟的振荡。双光子钙成像显示缰核神经元的自发活动存在昼夜节律变化。为了评估这个生物钟的作用，一个截短的基因在缰核中特异性表达。这部分抑制了生物钟，表现为基因表达的变化以及多巴胺、血清素和乙酰胆碱水平的昼夜变化改变。在行为上，警报信息素引发的焦虑样反应减少。信息素的昼夜节律效应被破坏，使得白天的反应类似于夜间的反应。由松果体生物钟调节且不受应激源触发的行为未受影响。我们认为缰核生物钟调节对危险的预期，从而为对应激源反应的昼夜节律变化提供了一种机制。
