McKillop Laura E, Vyazovskiy Vladyslav V
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Handb Exp Pharmacol. 2019;253:97-121. doi: 10.1007/164_2018_174.
Wakefulness and sleep are highly complex and heterogeneous processes, involving multiple neurotransmitter systems and a sophisticated interplay between global and local networks of neurons and non-neuronal cells. Macroscopic approaches applied at the level of the whole organism, view sleep as a global behaviour and allow for investigation into aspects such as the effects of insufficient or disrupted sleep on cognitive function, metabolism, thermoregulation and sensory processing. While significant progress has been achieved using such large-scale approaches, the inherent complexity of sleep-wake regulation has necessitated the development of methods which tackle specific aspects of sleep in isolation. One way this may be achieved is by investigating specific cellular or molecular phenomena in the whole organism in situ, either during spontaneous or induced sleep-wake states. This approach has greatly advanced our knowledge about the electrophysiology and pharmacology of ion channels, specific receptors, intracellular pathways and the small networks implicated in the control and regulation of the sleep-wake cycle. Importantly though, there are a variety of external and internal factors that influence global behavioural states which are difficult to control for using these approaches. For this reason, over the last few decades, ex vivo experimental models have become increasingly popular and have greatly advanced our understanding of many fundamental aspects of sleep, including the neuroanatomy and neurochemistry of sleep states, sleep regulation, the origin and dynamics of specific sleep oscillations, network homeostasis as well as the functional roles of sleep. This chapter will focus on the use of small neuronal networks as experimental models and will highlight the most significant and novel insights these approaches have provided.
觉醒和睡眠是高度复杂且异质的过程，涉及多个神经递质系统以及神经元和非神经元细胞的全局与局部网络之间复杂的相互作用。在整个生物体水平上应用的宏观方法，将睡眠视为一种全局行为，并有助于研究诸如睡眠不足或睡眠中断对认知功能、新陈代谢、体温调节和感觉处理的影响等方面。虽然使用这种大规模方法已取得了显著进展，但睡眠 - 觉醒调节的内在复杂性使得有必要开发能够单独处理睡眠特定方面的方法。实现这一点的一种方法是在自发或诱导的睡眠 - 觉醒状态下，在整个生物体原位研究特定的细胞或分子现象。这种方法极大地推进了我们对离子通道、特定受体、细胞内途径以及参与睡眠 - 觉醒周期控制和调节的小网络的电生理学和药理学的认识。然而重要的是，存在多种外部和内部因素会影响全局行为状态，而使用这些方法很难对其进行控制。因此，在过去几十年中，离体实验模型越来越受欢迎，并极大地推进了我们对睡眠许多基本方面的理解，包括睡眠状态的神经解剖学和神经化学、睡眠调节、特定睡眠振荡的起源和动态、网络稳态以及睡眠的功能作用。本章将重点介绍使用小型神经元网络作为实验模型，并突出这些方法所提供的最重要和新颖的见解。
