Developmental Genetics of the Nervous System, Max Planck Institute for Medical Research Heidelberg, Germany.
Front Neural Circuits. 2013 May 6;7:82. doi: 10.3389/fncir.2013.00082. eCollection 2013.
The stress response is a suite of physiological and behavioral processes that help to maintain or reestablish homeostasis. Central to the stress response is the hypothalamic-pituitary-adrenal (HPA) axis, as it releases crucial hormones in response to stress. Glucocorticoids (GCs) are the final effector hormones of the HPA axis, and exert a variety of actions under both basal and stress conditions. Despite their far-reaching importance for health, specific GC effects have been difficult to pin-down due to a lack of methods for selectively manipulating endogenous GC levels. Hence, in order to study stress-induced GC effects, we developed a novel optogenetic approach to selectively manipulate the rise of GCs triggered by stress. Using this approach, we could induce both transient hypercortisolic states and persistent forms of hypercortisolaemia in freely behaving larval zebrafish. Our results also established that transient hypercortisolism leads to enhanced locomotion shortly after stressor exposure. Altogether, we present a highly specific method for manipulating the gain of the stress axis with high temporal accuracy, altering endocrine and behavioral responses to stress as well as basal GC levels. Our study offers a powerful tool for the analysis of rapid (non-genomic) and delayed (genomic) GC effects on brain function and behavior, feedbacks within the stress axis and developmental programming by GCs.
应激反应是一套生理和行为过程，有助于维持或重新建立体内平衡。应激反应的核心是下丘脑-垂体-肾上腺（HPA）轴，因为它会在应激时释放关键激素。糖皮质激素（GCs）是 HPA 轴的最终效应激素，在基础和应激条件下发挥多种作用。尽管它们对健康具有深远的重要性，但由于缺乏选择性操纵内源性 GC 水平的方法，特定的 GC 效应一直难以确定。因此，为了研究应激诱导的 GC 效应，我们开发了一种新的光遗传学方法来选择性地操纵应激引发的 GC 升高。使用这种方法，我们可以在自由活动的幼虫斑马鱼中诱导短暂的高皮质醇状态和持续的高皮质醇血症。我们的结果还表明，短暂的高皮质醇血症会导致应激暴露后短时间内运动能力增强。总之，我们提出了一种高度特异性的方法，可以高精度地操纵应激轴的增益，改变应激和基础 GC 水平对内分泌和行为的反应。我们的研究为分析 GC 对大脑功能和行为的快速（非基因组）和延迟（基因组）效应、应激轴内的反馈以及 GC 的发育编程提供了一个强大的工具。
