Phasis influences during REM sleep upon dorsal lateral geniculate nucleus unit activity in the rat

The single unit activity of dorsal lateral geniculate nucleus cells was recorded in freely moving, unanesthetized albino rats and studied in relation to the sleep-wake cycle and the occurreence of REM sleep ponto-geniculo-occipital (PGO) waves. Spontaneous mean discharge rates are shown to be significantly related to sleep-wake stages, and 70 percent of the units demonstrate a temporal relationship with hindbrain PGO waves. These data are consistent with the existence of a phasic event system in the rat.     

Sharply contoured theta waves are the human correlate of ponto-geniculo-occipital waves in the primary visual cortex

Objective

Ponto-geniculo-occipital (PGO) waves occurring along the visual axis are one of the hallmarks of REM sleep in experimental animals. In humans, direct evidence is scarce. There is no systematic study of PGO waves in the primary visual cortex.

Neuronal activity in the lateral geniculate nucleus associated with ponto-geniculo-occipital waves lacks lamina specificity

Ponto-geniculo-occipital (PGO) waves are spontaneously occurring field potentials recorded in the dorsal lateral geniculate nucleus (LGN) just prior to and during rapid eye movement (REM) sleep. Facilitated discharge rates of LGN neurons are associated with PGO waves. In kittens during the critical period of visual system development, both visual experience and PGO waves appear capable of influencing the course of development through activity-dependent mechanisms. Retinal innervation of LGN segregates into eye-specific laminae and is critical to supporting the role of binocular visual experience in development. We sought to determine whether neuronal activity associated with PGO waves also exhibits lamina specificity. PGO wave-related discharges were examined in LGN neurons identified as to lamina location in adult cats administered urethane anesthesia and the reserpine-like compound, RO4-1284. Spontaneous activity of LGN neurons was related to the occurrence of PGO-like waves in all cells studied. No factors could be found that differentiated lamina location and PGO wave-related discharges. We conclude that the PGO wave influence on neuronal activity in the visual system is fundamentally different from that derived from visual experience. The implications of this difference for the role of the two sources of activation in the control of neural activity in development are discussed.     

Manipulating REM sleep in older adults by selective REM sleep deprivation and physiological as well as pharmacological REM sleep augmentation methods

Experimental approaches to manipulate REM sleep within the cognitive neuroscience of sleep are usually based on sleep deprivation paradigms and focus on younger adults. In the present study, a traditional selective REM sleep deprivation paradigm as well as two alternative manipulation paradigms targeting REM sleep augmentation were investigated in healthy older adults. The study sample consisted of 107 participants, male and female, between the ages of 60 and 82 years, who had been randomly assigned to five experimental groups. During the study night, a first group was deprived of REM sleep by selective REM sleep awakenings, while a second group was woken during stage 2 NREM sleep in matched frequency. Physiological REM sleep augmentation was realized by REM sleep rebound after selective REM sleep deprivation, pharmacological REM sleep augmentation by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Deprivation and augmentation paradigms manipulated REM sleep significantly, the former affecting more global measures such as REM sleep minutes and percentage, the latter more organizational aspects such as stage shifts to REM sleep, REM latency, REM density (only pharmacological augmentation) and phasic REM sleep duration. According to our findings, selective REM sleep deprivation seems to be an efficient method of REM sleep manipulation in healthy older adults. While physiological rebound-based and pharmacological cholinergic REM sleep augmentation methods both failed to affect global measures of REM sleep, their efficiency in manipulating organizational aspects of REM sleep extends the traditional scope of REM sleep manipulation methods within the cognitive neuroscience of sleep.     

Increasing PGO spike density by auditory stimulation increases the duration and decreases the latency of rapid eye movement (REM) sleep

The purpose of this study was to determine whether ponto-geniculo-occipital (PGO) spikes play a role in triggering or maintaining sleep. During the recording of the sleep cycle of cats, the appearance of the first PGO spike automatically triggered an auditory stimulus through a speaker placed in the cat's recording cage. The effect of this procedure was compared to similar period when no such stimulus was given. The results showed that the auditory stimulus increased PGO spike density during REM sleep. It also produced a spectacular increase in the duration of REM, while decreasing the latency of its appearance from the first PGO spike. It is suggested that the auditory stimulus reinforces the 'PGO system', which in turn may function as a pace-setter for priming and maintaining REM sleep.     

Effects of electrical stimulation in the amygdala on ponto-geniculo-occipital waves in rats

We examined the role of the amygdala in the modulation of sleep and ponto-geniculo-occipital (PGO) waves in the rat. The amygdala projects massively, via its central nucleus, into brainstem regions involved in alerting and in the generation of rapid-eye movement (REM) sleep and PGO waves. Electrical stimulation of the central nucleus of the amygdala during REM sleep increased PGO wave amplitude. Stimulation during non-REM sleep decreased PGO wave frequency. The results indicate that the amygdala has a role in modulating brainstem neural mechanisms underlying alerting during sleep.     

Cholinergic reduction of REM sleep duration is reverted by auditory stimulation

It was previously shown that an auditory stimulus given prior to and throughout a rapid eye movement (REM) sleep period was capable of inducing a significant increase in REM sleep duration and pontogeniculo-occipital (PGO) spike density. The purpose of this study was to determine whether the increase in REM duration is dependent on PGO spike density. We administered atropine to cats at doses of 0.1–0.6 mg/kg and the effects on REM duration and PGO spikes was determined. The doses of 0.2 and 0.3 mg/kg of atropine were then utilized to compare REM sleep periods with and without auditory stimulation. The results showed that both REM duration and PGO spikes were decreased by atropine, but could be dissociated from each other depending on the doses. In addition, it was shown that the auditory stimulus protected the animals from the effects of atropine but only in relation to REM sleep duration. The results indicate that both REM sleep duration and PGO spikes have a cholinergic component and that the auditory stimulus exerts its REM enhancing properties in a manner which seems to be independent of the PGO spike density. The results are discussed in terms of receptor availability and/or excitability levels of medial reticular neurons.     

Phase-locking of spontaneous and elicited ponto-geniculo-occipital waves is associated with acceleration of hippocampal theta waves during rapid eye movement sleep in cats

We investigated the temporal relationship between hippocampal theta waves and ponto-geniculo-occipital waves (PGO) during rapid eye movement sleep (REM sleep) in cats. In addition, we analyzed the relationship between hippocampal theta waves and PGO as elicited by tone stimulus (PGO(E)) in order to quantitively characterize the PGO wave generator mechanism. The results showed that a spontaneous PGO tended to be phase-locked to the theta wave, which was more clearly observed in the single PGO than in the cluster. However, cluster PGO(E) tended to be phase-locked as well as single PGO(E). It was therefore suggested that the generator of PGO is activated in relation to the hippocampal theta wave. An acceleration of the theta wave associated with PGO occurrence was found, and was more markedly observed than with the cluster PGO. Although the magnitude of it was less than in the spontaneous case, an acceleration around the PGO(E) was also observed. These results suggest that the generators of theta and PGO receive some common activations, especially when a cluster PGO is generated. The interaction between PGO and hippocampal theta waves is expected to be involved in the possible functions of REM sleep.     

Differential enhancement of rapid eye movement sleep signs in the cat: a comparison of microinjection of the cholinergic agonist carbachol and the β-adrenergic antagonist propranolol on pontogeniculo-occipital wave clusters

The cholinergic agonist carbachol and the β-adrenergic antagonist propranolol were microinjected at the same pontine sites and their effects on polygraphic rapid eye movement (REM) sleep, especially pontogeniculo-occipital (PGO) waves, were measured. While both propranolol and carbachol enhanced PGO wave activity and polygraphic REM sleep, the carbachol-correlated enhancement was more impressive. The increases in REM sleep signs elicited by carbachol were 5-fold over baseline and lasted throughout the 4-h recording period. Propranolol elicited 2.5-fold increases that were significant in the first 2 h only. Yet, the increase in PGO wave activity evoked by propranolol was equal to that of carbachol during non-REM sleep and wakefulness. The results indicate that while propranolol is less potent in activating the distributed neuronal network responsible for REM sleep generation, it selectively facilitates that part of the network responsible for PGO waves.     

REM sleep enhancement induced by sensory stimulation is prevented by kainic acid lesion of the pontine reticular formation

It has been shown that auditory or somatic stimulation during rapid eye movement (REM) sleep is capable of producing a significant increase in ponto-geniculo-occipital (PGO) spike density as well as in REM sleep duration. The purpose of this study was to determine the role of the medial pontine reticular formation (PRF) in mediating such increase of REM sleep duration. After a baseline recording whereby on the same recording day the control and the stimulus (auditory or somatic) alternated with each REM, a group of cats was lesioned with kainic acid in the PRF. The sleep-wake cycle was recorded again on days 15, 30 and 45 post-lesion, following the same procedure. The results showed no changes in REM sleep duration and PGO spike density in the lesioned animals. However, when sensory stimulation was applied it was ineffective in producing REM sleep enhancement, although it was able to increase PGO spike density. These findings suggest that the effects of sensory stimulation on REM sleep duration are accomplished through the PRF, probably by inducing an increase in the excitability levels of such neurons, and further suggests that PGO spike density and REM duration are independent of each other.     

Spontaneous and elicited PGO spikes in rats

High-amplitude waves, similar in distribution and configuration to pontogeniculo-occipital (PGO) spikes recorded in cats, were recorded from the area of the locus coeruleus of chronically implanted, unanesthetized albino rats. The mean frequency of spiking during paradoxical sleep (PS) was 19 per min and the amplitudes of the spikes ranged from 0.07 to 0.28 mV. Based on these findings and those of a previous report, it was concluded that these spikes are homologous with PGO spikes recorded in cats. It was also found that spikes identical to the spontaneously occurring spikes of PS could be produced during wakefulness and in all states of sleep with external auditory stimulation. These elicited spikes were not accompanied by eye movements. Initial stimulus presentations resulted in EEG desynchronization, orienting movements and PGO spikes. With continued stimulus presentations, EEG and other signs of alerting would habituate followed by a gradual habituation of the spikes. The latency to the appearance of an evoked spike ranged from 20 to 24 msec. These findings are in agreement with recent studies in cats showing that PGO spikes occur in response to external, auditory stimuli in wakefulness and all stages of sleep in addition to their spontaneous occurrence just prior to and during PS.     

Metencephalic localization of ponto-geniculo-occipital waves in the albino rat

The dorsal pontine tegmentum was the center of an investigation of the metencephalic loci in which ponto-geniculo-occipital (PGO) waves were recorded in the albino rat. The characterization of electrophysiologic activity recorded from 45 electrodes was anatomically mapped on schematic coronal sections of the rat brain. The region of the nucleus locus ceruleus and nucleus tractus mesencephali consistently yielded PGO activity and the region immediately surrounding did not. Other sites where PGO activity was recorded include the lateral and dorsal aspects of the fasciculus longitudinalis medialis, the nucleus tegmenti ventralis von Gudden, and the anterior lobe of the cerebellum. These data demonstrate a widespread yet sometimes discrete set of loci for PGO activity and indicate that the mechanisms responsible for its appearance have widespread yet discrete influence.     

Inhibitory effect of state independent ponto-geniculo-occipital waves on seizure occurrence induced by local application of penicillin into the temporal lobe amygdala

PURPOSE: In order to explore the possible inhibitory role of the phasic phenomena of REM sleep ponto-geniculo-occipital (PGO) waves over epilepsy, seizure activity produced by topic administration of Na-penicillin (PCN) has been analyzed during sustained PGO waves irrespective of current state. PGO waves were induced by the injection of carbachol in the peribrachial area. METHODS: The development of acute experimental epilepsy was compared among nine chronically implanted, adult, male cats, by means of polygraphic 23h recordings. Our protocol consisted of sets of 4 trials: carbachol; PCN; carbachol followed by PCN and finally PCN followed by carbachol. Each cat received one single set and all trials were carried out with a seven days interval, in order to compare the epileptic activity both in the presence of PGOs and without them. RESULTS: PGO waves 1) exert an inhibitory influence over number and duration of the Generalized Convulsive Seizures (GCSs) and 2) spike frequency; 3) increase the latency of GCSs; and 4) restores sleep alterations produced by experimental epilepsy. CONCLUSIONS: PGO waves exhibit an inhibitory influence over seizures induced by PCN. These data support the hypothesis that this phasic phenomenon of REM sleep have a depressant effect on epilepsy, inhibit seizures and normalize sleep architecture changes induced by seizures. We suggest that one possible function of PGO activity is to protect the brain from intense changes in neuronal excitability; namely convulsive activity.     

Senior Vipassana Meditation practitioners exhibit distinct REM sleep organization from that of novice meditators and healthy controls

Abstract/Summary

The present study is aimed to ascertain whether differences in meditation proficiency alter rapid eye movement sleep (REM sleep) as well as the overall sleep-organization. Whole-night polysomnography was carried out using 32-channel digital EEG system. 20 senior Vipassana meditators, 16 novice Vipassana meditators and 19 non-meditating control subjects participated in the study. The REM sleep characteristics were analyzed from the sleep-architecture of participants with a sleep efficiency index?>85%. Senior meditators showed distinct changes in sleep-organization due to enhanced slow wave sleep and REM sleep, reduced number of intermittent awakenings and reduced duration of non-REM stage 2 sleep. The REM sleep-organization was significantly different in senior meditators with more number of REM episodes and increased duration of each episode, distinct changes in rapid eye movement activity (REMA) dynamics due to increased phasic and tonic activity and enhanced burst events (sharp and slow bursts) during the second and fourth REM episodes. No significant differences in REM sleep organization was observed between novice and control groups. Changes in REM sleep-organization among the senior practitioners of meditation could be attributed to the intense brain plasticity events associated with intense meditative practices on brain functions.     

Relation of pontine choline acetyltransferase immunoreactive neurons with cells which increase discharge during REM sleep

The purpose of this study was to determine whether neurons in the medial pontine reticular formation with high discharge rates during REM sleep could be localized in regions of the brainstem having neurons displaying choline acetyltransferase immunoreactivity. Six cats were implanted with sleep recording electrodes and microwires to record extracellular potentials of neurons in the pontine reticular formation. Single-units with a S:N ratio greater than 2:1 were recorded for at least two REM sleep cycles. A total of 49 units was recorded from the pontine reticular formation at medial-lateral planes ranging from 0.8 to 3.7 mm. The greatest proportion of the units (28.6%) showed highest discharge during active waking and phasic REM sleep compared to quiet waking, non-REM sleep, transition into REM sleep or quiet REM sleep periods. A percentage (20.4%) of the cells had high discharge associated with phasic REM sleep periods while 8.2% of the cells showed a progressive increase in discharge from waking to REM sleep. Subsequent examination of the distribution of choline acetyltransferase immunoreactive cells in the PRF revealed that cells showing high discharge during REM sleep were not localized near presumed cholinergic neurons. Indeed, we did not find any ChAT immunoreactive somata in the medial PRF, an area which has traditionally been implicated in the generation of REM sleep. These results suggest that while increased discharge of PRF cells may be instrumental to REM sleep generation, these cells are not cholinergic.     

Sleep in depression: the influence of age,gender and diagnostic subtype on baseline sleep and the cholinergic REM induction test with RS 86

Summary One hundred and eight healthy controls and 178 patients with a major depressive disorder according to DSM-III were investigated in the sleep laboratory after a 7-day drug wash-out period. Subsamples of 36 healthy controls and 56 patients additionally took part in the cholinergic rapid eye movement (REM) sleep induction test with RS 86. Data analysis revealed that age exerted powerful influences on sleep in control subjects and depressed patients. Sleep efficiency and amount of slow wave sleep (SWS) decreased with age, whereas the number of awakenings, early morning awakening, and amounts of wake time and stage 1 increased with age. REM latency was negatively correlated with age only in the group of patients with a major depression. Statistical analysis revealed group differences for almost all parameters of sleep continuity with disturbed indices in the depressed group. Differences in SWS were not detected. REM latency and REM density were altered in depression compared to healthy subjects. Sex differences existed for the amounts of stage 1 and SWS. The cholinergic REM induction test resulted in a significantly more pronounced induction of REM sleep in depressed patients compared with healthy controls, provoking sleep onset REM periods as well in those depressed patients showing baseline REM latencies in the normal range. Depressed patients with or without melancholia (according to DSM-III) did not differ from each other, either concerning baseline sleep or with respect to the results of the cholinergic REM induction test. The results stress the importance of age when comparing sleep patterns of healthy controls with those of depressed patients. Furthermore they underline the usefulness of the cholinergic REM induction test for differentiating depressed patients from healthy controls and support the reciprocal interaction model of nonREM-REM regulation and the cholinergic-aminergic imbalance hypothesis of affective disorders.     

Intracortical inhibition and facilitation upon awakening from different sleep stages: a transcranial magnetic stimulation study

Intracortical facilitation and inhibition, as assessed by the paired-pulse transcranial magnetic stimulation technique with a subthreshold conditioning pulse followed by a suprathreshold test pulse, was studied upon awakening from REM and slow-wave sleep (SWS). Ten normal subjects were studied for four consecutive nights. Intracortical facilitation and inhibition were assessed upon awakening from SWS and REM sleep, and during a presleep baseline. Independently of sleep stage at awakening, intracortical inhibition was found at 1-3-ms interstimulus intervals and facilitation at 7-15-ms interstimulus intervals. Motor thresholds were higher in SWS awakenings, with no differences between REM awakenings and wakefulness, while motor evoked potential amplitude to unconditioned stimuli decreased upon REM awakening as compared to the other conditions. REM sleep awakenings showed a significant increase of intracortical facilitation at 10 and 15 ms, while intracortical inhibition was not affected by sleep stage at awakening. While the dissociation between motor thresholds and motor evoked potential amplitudes could be explained by the different excitability of the corticospinal system during SWS and REM sleep, the heightened cortical facilitation upon awakening from REM sleep points to a cortical motor activation during this stage.     

Long-term changes in sleep and electroencephalographic activity by chronic vagus nerve stimulation in cats

We previously reported the effect of vagus nerve electrical stimulation (VNS) on sleep and behavior in cats. The aim of the present study is to analyze the long-term effects of VNS on the electroencephalographic (EEG) power spectrum and on the different stages of the sleep-wakefulness cycle in the freely moving cat. To achieve this, six male cats were implanted with electrodes on the left vagal nerve and submitted to 15 rounds of 23 h continuous sleep recordings in three categories: baseline (BL), VNS and post-stimulus recording (PSR). The following parameters were analyzed: EEG power spectrum, total time and number of sleep phases, ponto-geniculo-occipital (PGO) wave density of the rapid eye movement (REM) sleep, and the number of times the narcoleptic reflex was present (sudden transition from wakefulness to REM sleep). Significant changes were detected, such as an enhancement of slow-wave sleep (SWS) stage II; a power increase in the bands corresponding to sleep spindles (8-14 Hz) and delta waves (1-4 Hz) with VNS and PSR; an increase in the total time, number of stages, and density of PGO wave in REM sleep with VNS; a decrease of wakefulness in PSR, and the eventual appearance of the narcoleptic reflex with VNS. The results show that the effect of the VNS changes during different stages of the sleep-wakefulness cycle. In REM sleep, the effect was present only during VNS, while the SWS II was affected beyond VNS periods. This suggests that ponto-medullar and thalamic mechanisms of slow EEG activity may be due to plastic changes elicited by vagal stimulation.     

Effects of REM sleep awakenings and related wakening paradigms on the ultradian sleep cycle and the symptoms in depression

In 1975 Vogel and coworkers published their classical study where they compared selective rapid eye movement (REM) sleep deprivation by brief awakenings to a control intervention paradigm in depressed patients. The superior antidepressive impact of the first procedure was attributed to the REM pressure accumulating during the treatment period. The laborious procedure and the considerable effort necessary to evaluate the sleep profiles in real time have prevented similar experiments so far. Based on artificial neural networks we developed a software for the real time detection of REM sleep. In combination with an alarm system the algorithm allowed us to wake up subjects automatically and to reduce REM sleep by about 50%. The procedure was then compared to a modified nonREM intervention paradigm for a treatment period of ten consecutive nights in depressed patients (n(1)=14, n(2)=13). These simultaneously received moderate dosages of Trimipramine. We found a strong and robust but not significantly different reduction of the average Hamilton rating scores (33 and 41% of baseline levels). While the REM sleep awakenings shortened the sleep cycle duration considerably, our nonREM intervention paradigm lengthened the ultradian alternations. Both effects might be interpreted as a challenge imposed on the nonREM-REM alternating mechanism possibly responsible for the antidepressive impact. A different timing of the control interventions might have caused the discrepancy between our findings and those of Vogel and coworkers.     

Comparison of Sleep Characteristics of Subjects in Their 70's with Those in Their 80's

Abstract: This study was undertaken to examine the effect of aging on sleep. All-night sleep polygrams of 15 subjects in their 70's and 11 subjects in their 80's were recorded for three consecutive nights. The increase in stage wakefulness (SW) and the decrease in stage 2 (S2) were significant in the subjects in their 80's in comparison with those in their 70's (p < 0.05, P < 0.01, respectively). After the age of 70, slow wave sleep decreased in the earlier part of the night and REM sleep shifted to the earlier part of the night. These facts support the hypothesis that slow wave sleep and REM sleep compete with each other.