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）节律，如睡眠-觉醒周期、进食、激素分泌、体温等，但也包括行为和大脑过程中更快的（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（光暗周期、季节），它们是由“生物钟”产生的，生物钟位于大脑和其他各种器官中。至于超昼夜节律，它们似乎依赖于大脑中分子的振荡，比如多巴胺。为了理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奏，并在不同的实验水平上进行监测。最近的技术进步允许使用细胞和组织，其中的生物发光分子，如荧光素酶，被跟踪许多天。这种系统能够实时评估样品的节奏特性，并确定受干扰的时钟装置的影响。这些信息可以与活体动物的记录相关联，在行为水平（运动活动节奏）和神经元回路水平（大脑中分子的节奏）。新的时间生物学设施将包括用于在行为（跑轮笼）、神经生物学（荧光光度法、伏特法）和细胞（实时光度计）水平上大规模研究生物节律的设备。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成分。三位申请人的实验室研究的所有方面，包括他们的NSERC发现资助的研究将受益于所申请的设备，这些设备将处于时间生物学研究的前沿。

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.