Recently, a novel type of fast cortical oscillatory activity that occurs between 110 and 160 Hz (high-frequency oscillations (HFO)) was described. HFO are modulated by the theta rhythm in hippocampus and neocortex during active wakefulness and REM sleep. As theta-HFO coupling increases during REM, a role for HFO in memory consolidation has been proposed. However, global properties such as the cortex-wide topographic distribution and the cortico-cortical coherence remain unknown. In this study, we recorded the electroencephalogram during sleep and wakefulness in the rat and analyzed the spatial extent of the HFO band power and coherence. We confirmed that the HFO amplitude is phase-locked to theta oscillations and is modified by behavioral states. During active wakefulness, HFO power was relatively higher in the neocortex and olfactory bulb compared to sleep. HFO power decreased during non-REM and had an intermediate level during REM sleep. Furthermore, coherence was larger during active wakefulness than non-REM, while REM showed a complex pattern in which coherence increased only in intra and decreased in inter-hemispheric combination of electrodes. This coherence pattern is different from gamma (30-100 Hz) coherence, which is reduced during REM sleep. This data show an important HFO cortico-cortical dialog during active wakefulness even when the level of theta comodulation is lower than in REM. In contrast, during REM, this dialog is highly modulated by theta and restricted to intra-hemispheric medial-posterior cortical regions. Further studies combining behavior, electrophysiology and new analytical tools are needed to plunge deeper into the functional significance of the HFO.
The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons of the lateral sector of the posterior hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR) and median (MR) raphe nuclei, which are involved in the control of sleep and mood. Major Depression (MD) is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability, and anhedonia. A short REM sleep latency (i.e., the interval between sleep onset and the first REM sleep period), as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline) and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons. Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD.
Ibogaine is a potent psychedelic alkaloid that has been the focus of intense research because of its intriguing anti-addictive properties. According to anecdotic reports, ibogaine has been originally classified as an oneirogenic psychedelic; i.e., induces a dream-like cognitive activity while awake. However, the effects of ibogaine administration on wakefulness (W) and sleep have not been thoroughly assessed. The main aim of our study was to characterize the acute effects of ibogaine administration on W and sleep. For this purpose, polysomnographic recordings on chronically prepared rats were performed in the light phase during 6 h. Animals were treated with ibogaine (20 and 40 mg/kg) or vehicle, immediately before the beginning of the recordings. Furthermore, in order to evaluate associated motor behaviors during the W period, a different group of animals was tested for 2 h after ibogaine treatment on an open field with video-tracking software. Compared to control, animals treated with ibogaine showed an increase in time spent in W. This effect was accompanied by a decrease in slow wave sleep (SWS) and rapid-eye movements (REM) sleep time. REM sleep latency was significantly increased in animals treated with the higher ibogaine dose. While the effects on W and SWS were observed during the first 2 h of recordings, the decrement in REM sleep time was observed throughout the recording time. Accordingly, ibogaine treatment with the lower dose promoted an increase on locomotion, while tremor and flat body posture were observed only with the higher dose in a time-dependent manner. In contrast, head shake response, a behavior which has been associated in rats with the 5HT2A receptor activation by hallucinogens, was not modified. We conclude that ibogaine promotes a waking state that is accompanied by a robust and long-lasting REM sleep suppression. In addition, it produces a dose-dependent unusual motor profile along with other serotonin-related behaviors. Since ibogaine is metabolized to produce noribogaine, further experiments are needed to elucidate if the metabolite and/or the parent drug produced these effects.
Disturbed sleep during gestation may lead to adverse outcomes for both mother and child. Animal research plays an important role in providing insights into this research field by enabling ethical and methodological requirements that are not possible in humans. Here, we present an overview and discuss the main research findings related to the effects of prenatal sleep deprivation in animal models. Using systematic review approaches, we retrieved 42 articles dealing with some type of sleep alteration.The most frequent research topics in this context were maternal sleep deprivation, maternal behaviour, offspring behaviour, development of sleep-wake cycles in the offspring, hippocampal neurodevelopment, pregnancy viability, renal physiology, hypertension and metabolism. This overview indicates that the number of basic studies in this field is growing, and provides biological plausibility to suggest that sleep disturbances might be detrimental to both mother and offspring by promoting increased risk at the behavioural, hormonal, electrophysiological, metabolic and epigenetic levels. More studies on the effects of maternal sleep deprivation are needed, in light of their major translational perspective.
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