An integrated chronobiology facility for the large-scale study of biological rhythms at the behavioural, neurocircuit and cellular levels

生理学的许多方面都表现出生物节律。这包括24小时（或昼夜）节律，如睡眠-觉醒周期，喂养，激素分泌，体温，仅举几例，但也包括行为和大脑过程中的更快（超昼夜）节律。昼夜节律使生物体能够充分适应环境的周期性变化（明暗周期，季节），它们是由位于大脑和其他各种器官中的“生物钟”产生的。至于超昼夜节律，它们似乎依赖于大脑中分子的振荡，如多巴胺。为了了解这些昼夜节律和超昼夜时钟是如何工作的，人们需要一种方法来实时监测它们的节律，并在各种实验水平上进行监测。最近的技术进步允许使用其中生物发光分子（例如荧光素酶）被跟踪许多天的细胞和组织。这种系统能够实时评估样本的节奏特性，并确定受干扰的钟表机构的影响。这些信息可以与在活体动物上进行的记录相关联，在行为水平（运动活动节律）和神经元回路水平（大脑中分子的节律）。新的时间生物学设施将包括在行为（转轮笼）、神经生物学（荧光光度测定法、伏安法）和细胞（实时光度计）各级进行生物节律大规模研究的设备。将有可能在这些不同的水平上测试相同的啮齿动物（小鼠，大鼠，田鼠），从而获得对其生物节律的综合看法。该设施还将允许大规模筛选，旨在发现生物钟的新分子组件。三个申请人实验室研究的所有方面，包括他们的NSERC发现赠款所涵盖的研究，都将受益于所要求的设备，这些设备将处于时间生物学研究的最前沿。

Numerous aspects of physiology present biological rhythms. This includes 24-hour (or circadian) rhythms such as sleep-wake cycles, feeding, hormone secretion, body temperature, to name a few, but also faster (ultradian) rhythms in behaviour and brain processes. The circadian rhythms allow the organism to be adequately adapted to cyclic variations of the environment (light-dark cycles, seasons), and they are generated by "biological clocks", which are located in the brain as well as in various other organs. As for the ultradian rhythms, they seem to rely on oscillations of molecules in the brain, such as dopamine. In order to understand how these circadian and ultradian clocks work, one needs a mean to monitor their rhythms in real-time and at various experimental levels. Recent technological advances allow the use of cells and tissues in which a bioluminescent molecule, e.g. luciferase, is followed over many days. This kind of system enables real-time assessment of the rhythmic properties of a sample, and to determine the effect of a disturbed clockwork. Such information can be put in relation with recordings made on live animals, at the behavioural level (locomotor activity rhythms) and neuronal circuit level (rhythms of molecules in the brain). The new chronobiology facility will include equipment for the large-scale study of biological rhythms at the behavioural (running wheel cages), neurobiological (fluorescence photometry, voltametry) and cellular (real-time luminometer) levels. It will be possible to test the same rodents (mice, rats, voles) at these different levels and thus gain an integrated view of their biological rhythms. This facility will also allow large-scale screenings designed to discover new molecular components of biological clocks. All the aspects of the research in the laboratories of the three applicants, including the research covered by their NSERC Discovery Grants will benefit from the requested equipment, which will be at the forefront of chronobiological research.