Onset Of Non-rapid Eye Movement Sleep Research Articles

Why do we sleep?

According to a simple behavioral definition, sleep is a reversible behavioral state of perceptual disengagement from and unresponsiveness to the environment. Sleep is dividing into two states: Non-rapid eye movement (NREM) sleep which is subdivided into three stages (N1, N2, N3); and rapid eye movement (REM) sleep characterized by rapid eye movements, muscle atonia and desynchronized EEG. Mammalian sleep and wake states are regulated by multiple neuronal systems located in the brainstem, diencephalon, and telencephalon. Wakefulness is maintained by activation of the ascending reticular activating system involving several neurotransmitters including glutamate, acetylcholine and the monoamines. NREM sleep onset is associated with a reduction in activation of the ascending reticular activating system and an increase in neural activity within the ventrolateral preoptic area, anterior hypothalamus and basal forebrain. REM sleep is triggered by activation of cholinergic neurons in the laterodorsal and pedunculopontine tegmental nuclei. The suppression of motor activity in REM sleep is generated by glutamate-mediated activation of descending medullary reticular formation. The two-process model postulates that a homeostatic process rises during waking and declines during sleep and interacts with a circadian process that is not directly dependent of sleep and waking. Sleep function remains controversial. Sleep is thought to be restorative, conservative, adaptive, thermoregulatory and memory consolidative functions. Sleep also serves host-defense mechanisms and conserves caloric expenditures. Emerging evidences indicated that sleep replenishes brain energy stores and that sleep serves a glymphatic function by removing toxic byproducts of waking activity. Finally, there is experimental evidence that connectivity changes with sleep, sleep loss, and with changing afferent input, and that those changes are linked to sleep regulatory mechanisms. Sleep medicine as a medical specialty has existed for more than 30 years. The study on over 90 kinds of sleep disorders has shed light on the understanding to the mechanisms of sleep. For example, the finding of the role of hypocretin/orexin in the patho-physiology of narcolepsy led to the reveal of hypocretin/orexin as a major wakefulness promoting substance. The evolution of the field will help us recognize the impact of sleep disorders on society as well as the nature of sleep itself.

Effect of dopamine D4 receptor agonists on sleep architecture in rats.

Dopamine plays a key role in the regulation of sleep-wake states, as revealed by the observation that dopamine-releasing agents such as methylphenidate have wake-promoting effects. However, the precise mechanisms for the wake-promoting effect produced by the enhancement of dopamine transmission are not fully understood. Although dopamine D1, D2, and D3 receptors are known to have differential effects on sleep architecture, the role of D4 receptors (D4Rs), and particularly the influence of D4R activation on the sleep-wake state, has not been studied so far. In this study, we investigated for the first time the effects of two structurally different D4R agonists, Ro 10-5824 and A-412997, on the sleep-wake states in rats. We found that both D4R agonists generally increased waking duration, and conversely, reduced non-rapid eye movement (NREM) sleep duration in rats. The onset of NREM sleep was also generally delayed. However, only the A-412997 agonist (but not the Ro 10-5824) influenced rapid eye movement sleep onset and duration. Furthermore, these effects were accompanied with an enhancement of EEG spectral power in the theta and the gamma bands. Our results suggest the involvement of dopamine D4R in the regulation of sleep-wake states. The activation of the D4R could enhance the arousal states as revealed by the behavioral and electrophysiological patterns in this study. Dopamine D4R may contribute to the arousal effects of dopamine-releasing agents such as methylphenidate.

Influence of sleep on alae nasi EMG and nasal resistance in normal men

The influence of sleep on the upper airway musculature varies considerably, with some muscles maintaining their activity at waking levels and others falling substantially. The influence of sleep on the alae nasi (AN), a dilator muscle of the nasal airway, has been minimally studied to date. Thus we determined the effect of non-rapid-eye-movement (NREM) sleep on the AN electromyogram and its relationship to nasal resistance (Rn) in nine normal supine males. Phasic inspiratory AN activity decreased from 20 +/- 6 arbitrary units during wakefulness to 5 +/- 1 arbitrary units (P < 0.001) at the onset of stage 2 NREM sleep and remained unchanged for two subsequent hours of NREM sleep. However, the Rn at the onset of NREM sleep remained similar to awake values (5.7 +/- 0.9 cmH2O.l-1 x s) and increased only after 1 h of NREM sleep (8.6 +/- 1.7 cmH2O.l-1 x s, P < 0.05), thus demonstrating little relationship to AN activity. We conclude that Rn increases slightly after 1 h of sleep, whereas AN activity decreases at stage 2 sleep onset. Thus AN activity has little influence on Rn during sleep.

The time course of σ activity and slow-wave activity during NREMS in cortical and thalamic EEG of the cat during baseline and after 12 hours of wakefulness

The extrapolation from recent neurophysiological findings concerning the dependency of spindle and slow-wave oscillations of thalamocortical neurons on membrane potential to macroscopic EEG events, predicts a reciprocal relation between spindle activity and slow-wave activity (SWA) in thalamic and cortical EEG during non-rapid-eye-movement sleep (NREMS). To test this hypothesis, the EEG recorded in 8 cats, from the nucleus centralis lateralis of the thalamus and from the skull during a 12-h baseline dark period and during a 12-h recovery dark period, following a 12-h sleep deprivation, were analyzed. Per 12-h epoch, sleep-wake behaviour was determined and spectral power density was computed in the slow-wave frequency range (0.5–4.0 Hz) and in the spindle frequency region (σ activity: 11.0–14.5 Hz). To analyze the development of EEG power densities in the course of NREMS and during the transition from NREMS to REMS, the last epoch of wakefulness and the first 15 epochs of NREMS, as well as the last epochs of NREMS and the first epoch of REMS were selected from the NREM-REM cycles. For each animal the values were averaged over 4-h intervals. In the cortical EEG, SWA was minimal at NREMS onset and increased progressively in the course of NREMS. SWA declined sharply prior to REMS, σ Activity increased gradually towards a uniform level after NREMS onset. During the transition to REMS, σ activity initially increased and then decreased rapidly. in the thalamic EEG, the time course of SWA paralleled that of the cortex. However, the development of σ activity during the first part of NREMS differed: in the thalamic EEG, σ activity was maximal during the beginning of NREMS and slightly decreased thereafter. After sleep deprivation, SWA within NREMS was markedly enhanced in both the cortical and the thalamic EEG. Sigma activity was attenuated in the thalamic EEG, whereas in the cortical EEG it was temporarily elevated. The present data show that, in the thalamic EEG, an inverse relation exists between spindle and slow-wave activity during baseline NREMS. This relation is preserved after sleep deprivation. In the cortical EEG, a reciprocal relation between spindling and SWA is less evident.

Ventral hippocampus spikes during sleep, wakefulness, and arousal in the cat.

The relationship between high amplitude (100--300- micro V) spike potentials (50--100 msec duration) in the ventral hippocampus (VH) and sleep-wakefulness stages was investigated. Forty-eight hours of continuous recordings taken from 5 chronically implanted cats were quantitatively scored for stage by digitized outputs of integrated EEG and electromyographic signals and for VH spikes by automatic devices. (1) A very strong relationship was observed between VH spike rates and EEG stage. Spikes were rare during wakefulness and paradoxical sleep (PS). They were always most frequent during nonrapid eye movement (NREM) sleep stages, progressively increasing through drowsiness, moderate amplitude slow wave activity, and high amplitude slow wave activity. (2) VH spike rates varied inversely with level of behavioral arousal within wakefulness. Rates were lowest during the presentation of novel experimental stimuli, higher during spontaneous movement, and highest during quiet wakefulness. (3) VH spikes anticipated stage changes independent of the quantified EEG. Spike rates increased from previous baseline levels in the 30 sec epoch of waking immediately preceding NREM sleep onset and in the transition period between PS and NREM sleep. They decreased significantly from previous base-line levels in the 30 sec epoch of NREM sleep preceding either waking or PS. These results show that the VH spike is a potentially useful noncortical indicator of NREM sleep. Within wakefulness and in the anticipation of stage changes it can be a more sensitive indicator of sleep processes or arousal level than the EEG.