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 clocka gene was specifically expressed in the habenula. This partially inhibited the clock, as shown by changes in per3 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.

动物对感官刺激的反应取决于刺激的性质和期望，而期望是由自发活动介导的。在这里，我们询问如何控制对危险预期的昼夜节律变化，从而控制对潜在威胁的反应。我们专注于缰核，一种通过调节神经调节剂释放起作用的威胁反应介质，并使用斑马鱼作为实验系统。单细胞转录组学表明在整个缰核中表达了多个时钟基因，而定量原位杂交证实了时钟振荡。双光子钙成像表明缰核神经元自发活动的昼夜节律变化。为了评估这个时钟的作用，一个被截断的时钟基因在缰核中特异性表达。这部分抑制了时钟，如per3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变化所示。在行为上，由警报信息素引起的类似焦虑的反应减少了。信息素的昼夜节律效应被打乱，因此白天的反应与晚上的反应相似。由松果体钟调节而不是由压力源触发的行为不受影响。我们建议缰核时钟调节对危险的预期，从而为对压力源的反应的昼夜节律变化提供一种机制。