What single‐unit recording studies tell us about the basic mechanisms of sleep and wakefulness

Abstract

This paper reviews the presence, localization and characteristics of state-specific neurons in the mouse forebrain, midbrain and hindbrain that are involved in the control of ultradian sleep-wake cycles and shows that all these regions contain basic neural elements capable of generating the sleep-wake cycle. The chronic single-unit recording method in unanaesthetized animals is useful for unravelling the dynamics of sleep-wake switching, in particular because it can analyse events at the level of single neurons, thereby decoding information used by the brain in determining its functional state. A prerequisite is to record a large number of all types of neurons, identify critical wake-and sleep-promoting neurons and determine their activity profiles during the sleep-wake cycle and their trends in spike activity during the state transitions from wakefulness to sleep and from sleep to wakefulness in the same species. Here, I argue that single-unit recordings in unanaesthetized mice help us to (a) determine key neural elements controlling sleep-wake dynamics, (b) elucidate the roles of forebrain and brainstem neurons in ultradian sleep-wake cyclicity and (c) gain a new insight into the functional significance of wakefulness, slow-wave sleep and paradoxical (or rapid eye movement) sleep. I also discuss the merits and limitations of single-unit recording compared with more recent genetic approaches, and I suggest that findings from studies using the classic electrophysiological technique will provide the foundation for future studies using new genetic techniques to dissect the neural networks responsible for the initiation, maintenance and cessation of each wake and sleep state. K E Y W O R D S dynamics of sleep-wake switching, forebrain and brainstem neurons, sleep/wake-specific neurons, ultradian sleep-wake cyclicity, unanaesthetized mice 3508 | SAKAI 1 | INTRODUCTION The wakefulness (W)-sleep cycle is a biological phenomenon that is seen in most animals. In adult humans and other mammals, the sleep-wake cycle consists of a succession of W and two distinct states of sleep, referred to, respectively, as non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS)

Neurovascular coupling and bilateral connectivity during NREM and REM sleep

“…Sleep is a ubiquitous state in animals ( Anafi et al, 2019 ) that is controlled by an ensemble of nuclei and their brain-wide interactions ( Pace-Schott and Hobson, 2002 ; Sakai, 2020 ; Saper et al, 2010 ). In mammals ( Cirelli, 2009 ), sleep is broadly comprised of two stages: non-rapid eye movement (NREM or slow-wave sleep) and rapid eye movement (REM or paradoxical sleep) ( Weber and Dan, 2016 ).…”

Translational approaches to influence sleep and arousal

“…A transcriptional feedback loop within the SCN leads to ~24 hr cycles of activity ( Reppert and Weaver, 2001 ) which are transmitted to sleep-wake control neurons via intermediate neurons in the supraventricular zone and dorsomedial hypothalamus ( Saper et al, 2005 ). Silencing of wakefulness promoting neurons by homeostatic and circadian mechanisms leads to the disinhibition of GABAergic sleep-promoting neurons in several parts of the preoptic hypothalamus ( Lu et al, 2000 ; Sakai, 2020 ; Saper et al, 2001 ; Sherin et al, 1996 ; Szymusiak et al, 1998 ). Additional GABAergic neurons which promote NREM sleep are located in the cortex ( Gerashchenko et al, 2008 ; Morairty et al, 2013 ), lateral hypothalamus/zona incerta ( K. Liu et al, 2017 ; M. Liu et al, 2017 ) and parafacial region of the brainstem ( Anaclet et al, 2014 ).…”

Mapping Network Activity in Sleep

“…However, considering that sleep-wake are generated by subcortical neuronal populations, it is important to track longitudinally the activity of sub-cortical neurons, especially neurons implicated in generating wake, non-REM and REM sleep. Traditionally, standard electrophysiology has been used to identify activity of neurons during sleep and wake (Sakai, 2019). However, the limitations of in vivo microwire electrophysiology make it difficult to track neural activity over long periods.…”