Principal cell types of sleep–wake regulatory circuits

Abstract

Electrophysiological recordings indicate that neurons which discharge maximally in association with distinct sleep-wake states are distributed through the brain, albeit in differing proportions. As studied using juxtacellular recording and labeling within the basal forebrain, four functional principal cell types are distinguished as: wake/paradoxical sleep (W/PS)-, slow wave sleep (SWS)-, W- and PS-max active. They are each comprised by both GABA and glutamate neurons, in addition to acetylcholine neurons belonging to the W/PS group. By their discharge profiles and interactions, the GABA and glutamate neurons of different groups are proposed to have the capacity to generate sleep-wake states with associated EEG and EMG activities, though to also be importantly regulated by neuromodulatory systems, each of which belong to one functional cell group.

Neuronal Mechanisms for Sleep/Wake Regulation and Modulatory Drive

“…This brain structure has been traditionally regarded as a wake-promoting region, as its activation induce wakefulness and its lesion results in slow oscillations in the EEG and a coma-like state (Buzsaki et al, 1988;Fuller et al, 2011). Nonetheless, the BF is functionally and anatomically heterogeneous and contains intermingled neurons maximally active during different arousal states (Jones, 2017). Cholinergic neurons of the BF are strongly activated during wakefulness and REM sleep (Boucetta et al, 2014;Lee et al, 2005a;Xu et al, 2015), and their optogenetic stimulation induces cortical activation and transitions from NREM sleep to wakefulness (Han et al, 2014;Irmak and de Lecea, 2014;Xu et al, 2015).…”

Coordinated activity of sleep and arousal neurons for stabilizing sleep/wake states in Drosophila

“…Our observations argue for a requirement of temporal segregation of the input of sleep-promoting SLP AstA /LPN AstA neurons and the TH-positive DAA neurons, which regulate dFSB AstAR1 neurons in an opposing fashion.An additional question is the mechanism through which dFSBAstAR1 neurons, which make up the effector arm of the Drosophila sleep-homeostatic circuit (Donlea et al, 2014; Liu et al, 2016), promote sleep. GABA is an inhibitory neurotransmitter,and has been linked to sleep promotion in flies and mammals(Agosto et al, 2008; Chung et al, 2017;Jones, 2017). We demonstrate that dFSB AstAR1 neurons use GABA as their sleep-promoting neurotransmitter.…”

Neural circuits linking sleep and addiction: animal models to understand why select individuals are more vulnerable to substance use disorders after sleep deprivation

“…Few studies have specifically focused on the role of the VP during sleep; however, the VP has been examined as part of the larger basal forebrain region, which has been shown to play a very important role in mediating both sleep and waking states (Jones 2017;Yang et al 2017). The basal forebrain describes a large area that encompasses the VP in addition to other subcortical structures, such as the medial septum, bed nucleus of the stria terminalis, substantia innominata, magnocellular preoptic nucleus, and extended amygdala (Yang et al 2017).…”

“…Among these cell types four different functional activity patterns have been identified. The most common type (˜50%) are cortically-projecting cells that show maximal firing during waking and REM sleep, but not NREM sleep (Jones 2017), and when optogenetically stimulated produces a rapid desynchronization of EEG and an increase in wakefulness (Irmak and de Lecea 2014;Xu et al 2015). The cholinergic neurons almost exclusively fall in this wake-promoting category (Lee et al 2005), as do most glutamatergic neurons and some parvalbumin-positive GABAergic neurons (Hassani et al 2009).…”

“…The fourth type (˜20%) is maximally responsive during REM sleep, but not waking. These are a mix of GABAergic and glutamatergic cells that project primarily to the posterior hypothalamus (Jones 2017). Although basal forebrain neurons have been well characterized in the context of sleep and wakefulness, it is not known whether there are individual differences in the composition or function of these different cell types.…”