Carbachol microinjections in the mediodorsal pontine tegmentum are unable to induce paradoxical sleep after caudal pontine and prebulbar transections in the cat.

In 7 cats, total transections of the brainstem at the caudal pontine or the prebulbar level led to preparations which presented neither behavioral nor electrophysiological signs of paradoxical sleep (PS) throughout their survival periods (17-30 days). Carbachol microinjections in the mediodorsal pontine tegmentum (MDPT), which induced PS in the intact cat, were no longer able to induce it in the transected animals. Rapid eye movement (REM) and pontogeniculo-occipital (PGO)-like bursts were evoked by carbachol microinjections in the pontine magnocellular tegmental field (FTM) of cats transected at the prebulbar level, as in the intact cat. Only REM bursts were obtained by the same injections in caudal pontine transected cats. It is concluded that (1) the pons is insufficient to generate PS; (2) complex reciprocal interactions with the medulla are necessary for the generation of this state of sleep; and (3) the production of long REM and PGO bursts is controlled by the caudal pontine tegmentum.     

The neurobiological characteristics of rapid eye movement (REM) sleep are candidate endophenotypes of depression, schizophrenia, mental retardation and dementia

Animal models are a promising method to approach the basic mechanisms of the neurobiological disturbances encountered in mental disorders. Depression is characterized by a decrease of REM sleep latency and an increase of rapid eye movement density. In schizophrenia, electrophysiological, tomographic, pharmacological and neurochemical activities are all encountered during REM sleep. Mental retardation and dementia are characterized by rather specific REM sleep disturbances. Identification of the genetic support for these abnormalities (endophenotypes) encountered during REM sleep could help to develop specific treatments.     

REM-NREM cycle in the cat may be sleep-dependent

The periodicity of the rapid eye movement-nonrapid eye movement (REM-NREM) cycle in real time versus compressed sleep was determined by autocorrelation, computed on the sequence of sleep stages in recordings from spontaneously sleeping cats. The resulting autocorrelation function was correlated to damped cosine waves, and the highest squared correlation coefficient (r2) was taken as indicating the most likely periodicity in the data entered for each animal. The periodicity of REM sleep was stronger (significantly higher r2) in the compressed sleep data than in the real-time data, indicating sleep dependency of the REM-NREM cycle. The REM-NREM cycle lengths determined by the autocorrelation technique were not significantly different for the real-time and compressed sleep data. The REM sleep episode interval, defined as the average interval between the start of successive REM sleep episodes, was significantly shorter for real-time sustained sleep than the cycle lengths as determined by the autocorrelation technique. A model is proposed which explains this phenomenon as due to fragmentation of REM sleep within the time periods with high probability for REM sleep. When such fragmentation occurs, the average REM sleep episode interval will not reflect an ultradian REM sleep periodicity.     

Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat

SUMMARY  Sleep and wakefulness were studied in rats following administration of a selective 5-HT_1A agonist (8-OH-DPAT), a non-selective 5-HT_1A antagonist [(-) pindolol] and a combination of 8-OH-DPAT and (—) pindolol.
8-OH-DPAT (1.0–4.0 μg) injected into the dorsal raphe nucleus increased slow-wave sleep and decreased wakefulness. Administration of the 5-HT_1A agonist by subcutaneous route induced biphasic effects such that low doses (0.010 mg kg^-1) decreased wakefulness and increased slow-wave sleep while higher doses (0.375 mg kg^-1) induced opposite effects. REM sleep was suppressed and REM latency was increased, what could be tentatively ascribed to a non-specific effect (hypothermia). (-) Pindolol (1.0–4.0 mg kg^-1) induced an initial increase of wakefulness and a decrease of NREM sleep and REM sleep. Thereafter, NREM sleep showed a marked increase while REM sleep remained depressed. Pretreat-ment with (—) pindolol reversed the effects of both small and large doses of 8-OH-DPAT on slow-wave sleep and wakefulness.
The opposite effects, observed on the waking EEG after activation of either serotonin autoreceptors or postsynaptic 5-HT_1A receptors with adequate doses of 8-OH-DPAT, tend to indicate an active role for the 5-HT_1A receptor in the control of the waking state.     

Effects of the selective 5-HT1B agonist, CGS 12066B, on sleep/waking stages and EEG power spectrum in rats

SUMMARY  Sleep/waking stages and EEG power spectra were studied in rats for 8 h following intraperitoneal administration of CGS 12066B, a selective 5-HT_1B agonist. Waking was increased and rapid eye movement (REM) sleep decreased in a dose-dependent manner. Total slow-wave sleep (TSWS) was reduced, but only in the first 2 h period. The latencies to REM sleep and stable sleep were increased dose-dependently. The drug also induced profound behavioural changes that may account for some of the sleep/waking changes. EEG power densities in waking and TSWS were reduced dose-dependently from 7 to 20 Hz after CGS 12066B, suggesting a tendency towards general deactivation. The increase in waking together with a general deactivation suggest complex effects of CGS 12066B on the sleep/waking axis.     

Phasic changes in motoneuron membrane potential during REM periods of active sleep

Most of the phasically occurring periods of rapid eye movements (REMs) of active sleep are accompanied by enhanced suppression of somatomotor activity; however, during some of the REM episodes there are muscular twitches and jerks. The membrane potential changes underlying these motor processes were examined by recording intracellularly from lumbar motoneurons in cats that were undrugged, unanesthetized and normally respiring. Summated hyperpolarizing potentials were evident during REM episodes in conjunction with a decrease in motoneuron excitability. During other episodes of REMs there occurred summated depolarizing potentials which occasionally produced action potentials. These depolarizing events were in most cases preceded by a brief period of hyperpolarization. Thus, it appears that there is inhibitory input to lumbar motoneurons during all REM periods of active sleep; in some episodes the simulataneous coactivation of excitatory input leads to depolarization of the membrane and action potential generation.     

Evidence for a role of basal ganglia in the regulation of rapid eye movement sleep by electrical and chemical stimulation for the pedunculopontine tegmental nucleus and the substantia nigra pars reticulata in decerebrate cats

The present study was to determine how afferents from the substantia nigra pars reticulata (SNr) of the basal ganglia to the pedunculopontine tegmental nucleus (PPN) in the brainstem could contribute to the control of behavioral states. We used anesthetized and acutely decerebrated cats (n=22). Repetitive electrical stimulation (10-100 Hz, 20-50 microA, for 4-20 s) to the ventrolateral part of the PPN produced rapid eye movement (REM) associated with a suppression of postural muscle tone (REM with atonia). Although repetitive electrical stimuli (10-200 Hz, 10-60 microA, for 5-20 s) delivered to the dorsolateral part of the SNr did not evoke eye movements or muscular tonus in baseline conditions, it altered the PPN-induced REM with atonia. The following three types of effects were induced: (1) attenuation of the REM with atonia; (2) attenuation of muscular atonia without changes in REM (REM without atonia); and (3) attenuation of only REM. The optimal stimulus sites for these effects were intermingled within the lateral part of the SNr. The PPN-induced REM with atonia was abolished by an injection into the PPN of muscimol (1-15 mM, 0.1-0.25 microl), a GABAA receptor agonist, but not altered by an injection of baclofen (1-10 mM, 0.1-0.25 microl), a GABAB receptor agonist. Moreover, an injection of bicuculline (1-15 mM, 0.1-0.25 microl), a GABAA receptor antagonist, into the PPN, resulted in REM with atonia. On the other hand, an injection of muscimol into the dorsolateral part of the SNr (1-15 mM, 0.1-0.25 microl) induced REM with atonia, which was in turn eliminated by a further injection of muscimol into the PPN (5-10 mM, 0.2-0.25 microl). These results suggest that a GABAergic projection from the SNr to the PPN could be involved in the control of REM with atonia, signs which indicate REM sleep. An excessive GABAergic output from the basal ganglia to the PPN in parkinsonian patients may induce sleep disturbances, including a reduction of REM sleep periods and REM sleep behavioral disorders (REM without atonia).     

Phasic activity of the basolateral amygdala, cingulate gyrus, and hippocampus during REM sleep in the cat

We analyzed the electrical activity of the basolateral amygdala (BLA), anterior and posterior regions of the cingulate gyrus (A-CG and P-CG), the dorsal hippocampus (DH), the anterior ventral thalamic nucleus (AVTN), and the sensory motor cortex during the rapid eye movements and ponto-geniculo-occipital (PGO) activity of REM sleep in cats in chronic preparation. Polygraphic recordings and computational perievent averages using the phasic contractions of the lateral rectus muscle (LR) of the eyeball as the triggering signal of the analysis were performed. We observed biphasic potentials (200-300 ms) of variable amplitude, related to the phasic phenomena of REM sleep, in the BLA, A-CG, P-CG, DH, and AVTN. The latencies of the potentials of these regions were always greater than those of the geniculate PGO activities. We propose that the recorded limbic potentials resulted from propagation of PGO activity and that this phenomenon may reflect the limbic structure of the hallucinatory, vegetative, and emotional components of REM sleep.     

Intrinsic dreams are not produced without REM sleep mechanisms: evidence through elicitation of sleep onset REM periods

The hypothesis that there is a strict relationship between dreams and a specific rapid eye movement (REM) sleep mechanism is controversial. Many researchers have recently denied this relationship, yet none of their studies have simultaneously controlled both sleep length and depth prior to non-REM (NREM) and REM sleep awakenings, due to the natural rigid order of the NREM--REM sleep cycle. The failure to control sleep length and depth prior to arousal has confounded interpretations of the REM-dreams relationship. We have hypothesised that different physiological mechanisms underlie dreaming during REM and NREM sleep, based on recent findings concerning the specificity of REM sleep for cognitive function. Using the Sleep Interruption Technique, we elicited sleep onset REM periods (SOREMP) from 13 normal subjects to collect SOREMP and sleep onset NREM (NREMP) dreams without the confounds described above. Regression analyses showed that SOREMP dream occurrences were significantly related to the amount of REM sleep, while NREMP dream occurrences were related to arousals from NREM sleep. Dream properties evaluated using the Dream Property Scale showed qualitative differences between SOREMP and NREMP dream reports. These results support our hypothesis and we have concluded that although 'dreaming' may occur during both REM and NREM periods as previous researchers have suggested, the dreams obtained from these distinct periods differ significantly in their quantitative and qualitative aspects and are likely to be produced by different mechanisms.     

Cholinoceptive pontine reticular mechanisms cause state-dependent respiratory changes in the cat

This study tested the hypothesis that cholinoceptive regions of the medial pontine reticular formation (mPRF), long known to play a role in regulating the sleep cycle, can also causally alter the respiratory cycle. In 4 cats, sleep and wakefulness were polygraphically recorded while simultaneous measures were taken of rate of breathing, tidal volume, minute ventilation, respiratory cycle timing, and end-tidal CO2 concentration. Respiration during naturally occurring rapid eye movement (REM) sleep was compared to breathing during wakefulness and during the REM sleep-like state (D Carb) caused by mPRF microinjections of the cholinergic agonist carbachol. The results demonstrate for the first time that non-respiratory regions of the cholinoceptive mPRF can cause statistically significant state-dependent alterations in respiration.     

REM sleep predicts subsequent food intake.

REM sleep time in a 12 hr period was found to predict accurately food intake in the subsequent 12 hr period in undisturbed cats fed ad lib. In all but one of the cats, the correlation between REM sleep and subsequent food intake was negative. REM sleep was a better predictor of food intake than either waking, slow wave sleep or previous food intake. Cats were then fed only during the 12 hr day period. It was found that REM sleep at night, during which no food was available, no longer predicted food intake.     

Reduced sleep in cats after intraperitoneal injection of delta-sleep-inducing peptide (DSIP)

The effect of intraperitoneally injected delta-sleep-inducing peptide (DSIP) on sleep-wakefulness in cats was studied using EEG, EMG and EOG recording for 10 h following 30 nmol/kg DSIP or control saline i.p. injections. DSIP reduced the amount of sleep, specifically light slow-wave sleep and REM sleep, and REM sleep latency was increased. The results suggest that in cats with redundancy sleep DSIP increases wakefulness at the cost of light slow-wave sleep, and in addition it has a specific REM-reducing effect.     

Studies on sleep/wake effects of serotonin reuptake inhibitors and receptor subtype involvement

SUMMARY  Studies with the serotonin uptake inhibitors zimeldine and alaproclate show biphasic effects on the sleep/wake axis in rats and cats. Zimeldine induced an initial waking response succeeded by a small SWS-2 increase in rats. The waking increase was not blocked by the 5-HT₂ antagonist ritanserin nor by the putative 5-HT_1A antagonist (-)-alprenolol. In cats, zimeldine induced initial behavioural changes which were succeeded by a large SWS-2 increase. Alaproclate gave similar initial responses as zimeldine in both species, and was succeeded by a moderate sleep increase in cats but not in rats. The complex sleep/wake effects following the serotonin uptake inhibitors may result from simultaneous induction of incompatible serotonergic effects.     

Membrane potential of spinal motoneurons during natural sleep in cats.

The membrane potential of spinal motoneurons was recorded during wakefulness, NREM sleep, and REM sleep in minimally restrained, behaving cats. At the onset of sleep, the membrane potential generally increased in polarization in rough proportion to time spent asleep. During the postural atonia of REM sleep, the membrane potential of all motoneurons was tonically hyperpolarized. Antecedents of NREM sleep electromyographic suppressions, and REM sleep myoclonic twitches were seen as transient hyperpolarizations and depolarizations, respectively.     

Microinjections of nicotine in the medial pontine reticular formation elicits REM sleep

Microinfusion of non-specific cholinergic muscarinic-nicotinic agonists, such as carbachol, into the medial pontine reticular formation readily elicits REM sleep. It has generally been assumed that muscarinic receptors mediate the action of cholinergic agonists in triggering rapid eye movement (REM) sleep. Very little is known, however, about the role of nicotinic mechanisms in REM sleep generation. In this study, we administered nicotine and Ringer's solution into the medial pontine reticular formation of freely moving cats. Compared to control Ringer's injections, nicotine increased REM sleep and decreased wake and slow wave sleep (SWS) I percentage. Nicotine also shortened the time to REM sleep onset. These findings suggest a role of nicotinic mechanisms in REM sleep generation.     

Tonic and phasic phenomena underlying eye movements during sleep in the cat

Mammalian sleep is not a homogenous state, and different variables have traditionally been used to distinguish different periods during sleep. Of these variables, eye movement is one of the most paradigmatic, and has been used to differentiate between the so-called rapid eye movement (REM) and non-REM (NREM) sleep periods. Despite this, eye movements during sleep are poorly understood, and the behaviour of the oculomotor system remains almost unknown. In the present work, we recorded binocular eye movements during the sleep–wake cycle of adult cats by the scleral search-coil technique. During alertness, eye movements consisted of conjugated saccades and eye fixations. During NREM sleep, eye movements were slow and mostly unconjugated. The two eyes moved upwardly and in the abducting direction, producing a tonic divergence and elevation of the visual axis. During the transition period between NREM and REM sleep, rapid monocular eye movements of low amplitude in the abducting direction occurred in coincidence with ponto-geniculo-occipital waves. Along REM sleep, the eyes tended to maintain a tonic convergence and depression, broken by high-frequency bursts of complex rapid eye movements. In the horizontal plane, each eye movement in the burst comprised two consecutive movements in opposite directions, which were more evident in the eye that performed the abducting movements. In the vertical plane, rapid eye movements were always upward. Comparisons of the characteristics of eye movements during the sleep–wake cycle reveal the uniqueness of eye movements during sleep, and the noteworthy existence of tonic and phasic phenomena in the oculomotor system, not observed until now.     

Sleep patterning and behaviour in cats with pontine lesions creating REM without atonia

SUMMARY  Lesions of the dorsal pontine tegmentum release muscle tone and motor behaviour, much of it similar to orienting during wakefulness, into rapid eye movement sleep (REM), a state normally characterized by paralysis. Sleep after pontine lesions may be altered, with more REM-A episodes of shorter duration compared to normal REM. We examined behaviour, ponto-geniculo-occipital (PGO) waves (which may be central markers of orienting) and sleep in lesioned cats: (i) to characterize the relationship of PGO waves to behaviour in REM-A; (ii) to determine whether post-lesion changes in the timing and duration of REM-A episodes were due to activity-related awakenings; and (iii) to determine whether alterations in sleep changed the circadian sleep/wake cycle in cats. Behavioural release in REM-A was generally related to episode length, but episode length was not necessarily shorter than normal REM in cats capable of full locomotion in REM-A. PGO wave frequency was reduced overall during REM-A, but was higher during REM-A with behaviour than during quiet REM-A without overt behaviour. Pontine lesions did not significantly alter the circadian sleep/wake cycle; REM-A had approximately the same Light/Dark distribution as normal REM. Differences in the patterning of normal REM and REM-A within sleep involve more than mere movement-induced awakenings. Brainstem lesions that eliminate the atonia of REM may damage neural circuitry involved in REM initiation and maintenance; this circuitry is separate from circadian control mechanisms.     

Differential Effect of Sleep Deprivation on the Two Slow Wave Sleep Stages in the Gat

The effect of total sleep deprivation on the sleep stages and their interrelations was studied in 10 cats. EEG, EMG and eye movements were recorded for 24 h after 12 h and 24 h sleep deprivation and after no sleep deprivation. Sleep was divided into three stages: Light slow wave sleep (LSWS), deep slow wave sleep (DSWS) and rapid eye movement (REM) sleep. The total quantities of DSWS and REM sleep in the 24 h recordings increased with deprivation, as did the relative proportion (per cent of total sleep) of these sleep stages. The total quantity of LSWS did not change with sleep deprivation, and the LSWS per cent of total sleep decreased. The changes were most pronounced after 24 h deprivation and in the first hours of recovery sleep. Sleep deprivation reduced LSWS episode length and tended to increase DSWS and REM sleep episode length. The number of sleep cycles was increased, but the length of each cycle was not altered. The results support earlier findings of a functional dissociation between LSWS and DSWS and a functional relationship between DSWS and REM sleep.     

Nasal and sleep cycle--possible synchronization during night sleep

Regular cyclic changes in nostril airflow due to a nasal congestion and decongestion are known in literature as nasal cycle. Registration of breathing from each nostril separately gives possibility to registrate moments of alternative change of airflow of nostrils and periods of nasal cycle. This registration during night sleep shows that the length of these periods are about 1.5h, 3.0 h and 4.5h. The length of these periods are multiple of mean length of sleep cycle--about 1.5h. The alternative change of airflow through nostrils occurs through some of REM stages of the sleep. This shows, that during the night sleep becomes synchronization of nasal and sleep cycles in some of the REM phases of sleep. As a result--length of periods of the nasal cycle are one or more length of sleep cycle.     

Evidence that wakefulness and REM sleep are controlled by a GABAergic pontine mechanism.

The pontine microinjection of the inhibitory neurotransmitter GABA and its agonist induced prolonged periods of wakefulness in unanesthetized, chronic cats. Conversely, the application of bicuculline, a GABA(A) antagonist, resulted in the occurrence of episodes of rapid eye movement (REM) sleep of long duration. Furthermore, administration of antisense oligonucleotides against glutamic acid decarboxylase (GAD) mRNA into the same area produced a significant decrease in wakefulness and an increase in REM sleep. Microinjections of glycine, another major inhibitory neurotransmitter in the CNS, and its antagonist, strychnine, did not have any effect on the behavioral states of sleep and wakefulness. These data argue forcibly that 1) GABAergic neurons play a pivotal role in determining the occurrence of both wakefulness and REM sleep and 2) the functional sequelea of inhibitory GABA actions within the pontine reticular formation are excitatory directives and/or behaviors.