Learning and sleep: the sequential hypothesis

During the last 30 years, paradoxical sleep (PS) has been generally considered as the only type of sleep involved in memory processing, mainly for the consistent increase of PS episodes in laboratory animals learning a relatively complex task, and for the retention deficits induced by post-training PS deprivation. The vicissitudes of this idea, examined in detail by several laboratories, have been critically presented in a number of review articles However, according to a more comprehensive unitary proposal (the sequential hypothesis), memory processing during sleep does require the initial participation of slow-wave sleep (SS) in addition to the subsequent involvement of PS. The evidence supporting this hypothesis, largely derived from experiments concerning rats trained for a two-way active avoidance task, is reviewed here in some detail. Recent studies of human sleep are in full agreement with this view. In the rat, the main effect of learning on post-training SS consists in the selective increment in the average duration of SS episodes initiating different types of sleep sequences. Notably, following training for a two-way active avoidance task, the occurrence of this effect in sleep sequences including transition sleep (TS), such as SS→TS→W and SS→TS→PS, appears related to the processing of memories of the novel avoidance response. Conversely, the occurrence of the same effect in sleep sequences lacking TS may reflect the processing of memories of innate responses (escapes and freezings). Memories of innate and novel responses are assumed to engage in a dynamic competitive interaction to attain control of waking behaviour. Interestingly, in baseline sleep, variables of SS→TS→W and SS→TS→PS sequences, such as the average duration of SS, TS, and PS episodes, have proved to be good indices of the capacity to learn, as shown by their strong correlations with the number of avoidances scored by rats the following day. Comparable correlations have not been displayed by variables of baseline SS→W and SS→PS sequences.     

A Quantitative Study of Electroencephalography, Eye Movements and Neck Electromyography Characterizing the Sleep—Wake Cycle of the Guinea-pig

The qualitative and quantitative characteristics of cerebral cortex electrical activity, ocular motility and muscular activity were studied in six head-restrained guinea-pigs during wakefulness, slow-wave and paradoxical sleep. Animals were chronically implanted with bipolar electrodes in the obliquus capitis muscle for electromyographic recordings and epidurally through the parietal bones for electroencephalographic (EEG) recordings. Eye movements were recorded using the scleral search-coil technique. After postoperative recovery and a short period of habituation to immobilization, head-restrained animals exhibited a polyphasic sleep–wake cycle similar to what has already been described in the unrestrained guinea-pig. Paradoxical sleep periods of mean duration 110 ± 42 s occurred at a mean interval of 32.2 ± 7.2 min. Amplitude and frequency components of EEG activity were different for each state of vigilance. EEG amplitude was highest and frequency range lowest—with two well-defined peaks at 4 and 10 Hz—during slow-wave sleep. During paradoxical sleep, frequencies were higher and amplitudes lower than during wakefulness. Three types of eye movement intermingled with periods of ocular fixation were recorded: saccadic movements during wakefulness and paradoxical sleep, slow drifts during slow-wave sleep and paradoxical sleep, and a new type of eye movement—bursts of high-velocity eye oscillations during paradoxical sleep. Saccadic eye movements during paradoxical sleep were more frequent and showed higher velocities and amplitudes than during wakefulness. During paradoxical sleep the episodes of eye oscillation (8–14 Hz) occurred quite regularly every 1.6 s and had a mean duration of 1.4 s. During wakefulness, the obliquus muscle activity displayed a burst-tonic pattern. Bursting components were closely related to saccadic eye movements directed to the side of the recorded muscle. The muscle activity was predominantly tonic during slow-wave sleep and was completely absent during paradoxical sleep except for small bursts or twitches. These twitches were tightly synchronized with the occurrence of the rapid eye movements oriented towards the side of the recorded obliquus muscle, as during wakefulness. These results strongly suggest that paradoxical sleep is characterized by the oscillatory discharge of at least two neuronal populations: the brainstem saccadic generators and the tecto-reticular spinal network which underlies gaze-orienting behaviour during wakefulness. The occurrence of rhythmic discharges at ?11 Hz may explain the spinal motoneurons’ inhibition during paradoxical sleep in order to avoid anarchic motor behaviour. Whether these neuronal oscillations are simply an epiphenomenon or have functional implications remains to be determined.     

Identification of trains of sleep sequences in adult rats

In previous studies based on high resolution EEG analyses of the 7 h baseline session of 18 adult male Wistar rats [6,14], we have identified four sleep sequences initiating with slow wave sleep (SS) and terminating with waking (W) or paradoxical sleep (PS). Two of these sequences contained an intervening episode of transition sleep (TS). Several variables of these sequences (SS-->W, SS-->TS-->W, SS-->TS-->PS, and SS-->PS) were selectively correlated with the capacity of rats to learn a two-way active avoidance task the following day, and were differently distributed in fast learning, slow learning and non learning rats [21]. The temporal organization of different sleep components in sequences suggested that a comparable temporal organization might concern the different sleep sequences, albeit on a longer time scale. We have now used waking periods longer than 60 s to separate clusters of baseline sleep sequences (trains) in the same rats. Trains containing the same sleep sequence (homogeneous trains) have been distinguished from trains containing different sleep sequences (mixed trains). In addition, mixed trains including the SS-->TS-->W sequence (+TSW trains) have been separated from mixed trains lacking that sequence (-TSW trains). Mixed trains of the +TSW type were longest and most numerous, while homogeneous trains were shortest and least abundant. Mixed trains of the -TSW type displayed intermediate values. Several variables of sleep sequences and sleep components differed within mixed trains and among mixed and homogeneous trains. The data indicate that baseline sleep sequences aggregate in relatively long strings in a non random fashion. The mechanism of this association is discussed.     

Post-trial sleep sequences including transition sleep are involved in avoidance learning of adult rats

High resolution computerized EEG analyses, and behavioral observations were used to identify slow wave sleep (SS), paradoxical sleep (PS) and transition sleep (TS) in adult male Wistar rats exposed to a session of two-way active avoidance training. Of the four sleep sequences that could be identified, two included TS (SS-->TS-->W and SS-->TS-->PS), while the other two did not (SS-->W and SS-->PS). Comparison of post-trial sleep variables between fast learning rats (FL, reaching criterion in the training session), slow learning rats (SL, reaching criterion in the retention session the following day), and non learning rats (NL, failing to reach criterion) indicated that the total amounts of SS, TS and PS of the SS-->TS-->PS sequence was markedly higher in FL rats than in SL rats. In addition, in comparison with the corresponding baseline period, the average duration and total amount of SS and TS episodes of the SS-->TS-->PS sequence increased in FL rats, while the number of SS-->TS-->W sequences decreased. On the other hand, the average duration of SS episodes increased in the SS-->TS-->W and SS-->W sequences of SL rats, and in the SS-->W and SS-->TS-->PS sequences of NL rats. Correlative analyses between number of avoidances and post-trial sleep variables demonstrated that avoidances were directly correlated with the duration of SS episodes of the SS-->TS-->PS sequence and with the duration of TS episodes of the SS-->TS-->W sequence, but inversely correlated with the number and amount of SS episodes of the SS-->W sequence and with the duration and amount of SS episodes of the SS-->PS sequence. On the whole, the data supported the view that TS-containing sleep sequences are involved in long-term storage of novel adaptive behavior, while sleep sequences lacking TS are involved in the maintenance of innate behavioral responses.     

Activation of the phasic pontine-wave generator enhances improvement of learning performance: a mechanism for sleep-dependent plasticity

The aim of this study was to test the hypothesis that supplementary activation of the phasic pontine wave (P-wave) generator during rapid eye movement (REM) sleep enhances consolidation and integration of memories, resulting in improved learning. To test this hypothesis, two groups of rats were trained on a two-way active avoidance learning task in the morning. Immediately after training, one group of rats received a carbachol microinjection into the P-wave generator and the other group was microinjected with control saline into the same target area. After training trials and microinjections, rats were allowed a 6-h period of undisturbed sleep in the polygraphic recording chamber. At the end of 6 h of undisturbed sleep-wake recordings, rats were retested in a session of avoidance learning trials. After learning trials, the total percentage of time spent in REM sleep was significantly increased in both saline (15.36%)- and carbachol (17.70%)-microinjected rats. After learning trials, REM sleep P-wave density was significantly greater throughout the 6-h period of recordings in carbachol treated rats than in the saline treated rats. In the retrial session, the improvement in learning task performance was 22.75% higher in the carbachol-microinjected rats than in the saline-microinjected rats. These findings show that the consolidation and integration of memories create a homeostatic demand for P-waves. In addition, these findings provide experimental evidence, for the first time, that activation of the P-wave generator may enhance consolidation and integration of memories, resulting in improved performance on a recently learned task.     

Improvement of learning by cueing during postlearning paradoxical sleep

Rats were submitted to an active avoidance conditioning in a shuttle box with slight ear shocks used as conditioned stimulus (CS) preceding a foot shock. Three conditioning sessions were performed with a 24 h intersession interval. Animals were divided into 3 groups. After each session, the first group received the CS as cue during the first 6 phases of paradoxical sleep (PS) following learning. The second group received the CS as cue during 6 periods of wakefulness. The third group received no cue. Animals cued during PS showed a significant improvement in performances. The effect of cueing during the awake state appeared to be marginal compared to the clear-cut effects when the cue was presented during PS. A control experiment showed that the same ear shocks presented during PS were ineffective when they were not associated with the learning task (in this experiment a tone was used as CS during conditioning). These results are discussed in terms of memory reactivation during postlearning paradoxical sleep.     

Activation of phasic pontine-wave generator in the rat: a mechanism for expression of plasticity-related genes and proteins in the dorsal hippocampus and amygdala

A number of behavioral studies have emphasized the importance of interactions between the pontine-wave (P-wave) generator and the dorsal hippocampus (DH) in two-way active avoidance (TWAA) memory processing; however, the direct involvement of the P-wave generator in the TWAA training trial-induced molecular events in the DH and amygdala has not been systematically evaluated. Here we demonstrate that the TWAA learning training trials activate P-wave generator, and increase phosphorylation of CREB (pCREB) and expression of activity-regulated cytoskeletal-associated (Arc) protein, as well as messenger ribonucleic acid (mRNAs) of Arc, brain-derived nerve growth factor (BDNF) and early growth response-1 (Egr-1) in the DH and amygdala. Selective elimination of P-wave-generating cells abolished P-wave activity and suppressed TWAA learning training trial-induced expression of pCREB and Arc proteins and Arc, BDNF and Egr-1 mRNAs in the DH and amygdala. Following a session of TWAA training, all rats were equal in terms of time spent in wakefulness, slow-wave sleep and rapid eye movement (REM) sleep irrespective of P-wave lesions. The second set of experiments demonstrated that localized cholinergic stimulation of the P-wave generator increased expression of Arc, BDNF and Egr-1 mRNAs in the DH. Together, these findings provide the first direct evidence that activation of P-wave-generating cells is critically involved in the TWAA training trial-induced expression of plasticity-related genes in the DH and amygdala. These findings are discussed in relation to the role of P-wave generator activation for the REM sleep-dependent development and cognitive functions of the brain.     

Recording of electroencephalograms and electrocardiograms during daytime sleep in trained canines: Preparation of the sleeping dogs

Abstract  Although respiration in trained canines is well investigated, the process of preparing dogs has not been described in any great detail. Moreover, their daytime patterns of sleep and wakefulness during 1 or 2 h of electroencephalogram (EEG) and electrocardiogram (ECG) recordings are not clear. Therefore, we describe the process of selecting and training dogs, in which we recorded EEG and ECG in the laboratory. First, 14 of 1242 dogs dealt with over a 1 year period were chosen. They were trained for 2 h to lie quietly and to sleep in the laboratory; this training procedure was repeated 152 times. Three dogs were then selected and a permanent tracheostomy was performed in one. Finally, EEG and ECG were recorded with the bipolar fine needle electrodes; respiration was recorded simultaneously through a tube inserted to a tracheostomy in one dog. Wakefulness, slow wave sleep (SWS) and rapid eye movement (REM) sleep (REMS) were identified according to the EEG pattern and on the basis of the behavioral criteria. Recordings were performed 12 or 13 times in each dog. Complete sleep cycles, including wakefulness, SWS and REMS in this sequence, were observed 3.9–4.1 times. The mean duration of SWS was 2.2–4.4 min and that of REMS was 3.5–4.6 min. The REMS latency was 33.9–41.8 min. Fluctuation of heart rate with respiration, termed respiratory sinus arrhythmia, was noted in the ECG. Heart beat increased with inspiration and decreased with expiration. The present study demonstrates how to select and train sleeping dogs and shows their undisturbed daytime sleep and wakefulness patterns.     

Total calorimetric measurements in the rat: influences of the sleep-wakefulness cycle and of the environmental temperature

Rates of production as well as dry and evaporative heat loss during the sleep-wakefulness cycle were studied in 11 male, adult albino rats with chronically implanted electrodes and thermocouple re-entrant tubes. Two groups of animals chronically acclimated to 6 or 23 degrees C were acutely studied at 15, 20, 25, 30 and 35 degrees C. Statistical analysis of the data shows that rates of heat production and dry heat loss differ with respect to acclimation and acute environmental temperatures, and show significant differences depending on the states of the sleep-wakefulness cycle. Rate of heat production was highest during wakefulness, intermediate during synchronized sleep and lowest during paradoxical sleep. Rate of dry heat loss of 15 degrees C was maximal during paradoxical sleep. Rate of evaporative heat loss apparently did not change with the states of the sleep-wakefulness cycle. Heat storage estimated from difference in rates of heat production and heat loss was positive during wakefulness, slightly negative during synchronized sleep and markedly negative during paradoxical sleep. The data presented suggest a clear although partial suppression of thermoregulatory mechanisms during paradoxical sleep in the white rat.     

Sleep-wake states and cortical synchronization control by pregnenolone sulfate into the pedunculopontine nucleus

Cholinergic neurons of the pedunculopontine tegmentum nucleus (PPT) are crucial for initiation and maintenance of electroencephalographic (EEG) desynchronization states like paradoxical sleep and wakefulness. These neurons are regulated by classical neurotransmitter systems from the pontomesencephalic reticular formation and basal ganglia. In addition to this regulation, PPT neuron activity could be modulated by endogenous neurosteroids and particularly by pregnenolone sulfate (PREG-S) because synthesis enzymes of this neurosteroid are present in this area and peripheral administrations of PREG-S affect sleep-wakefulness states. To test this hypothesis, we studied the effects of different doses of PREG-S infusion into the PPT on sleep-wakefulness states in rats. Our results show dose-dependent effects of PREG-S on sleep-wakefulness states. Low concentration of PREG-S (5 ng) increased the amount of paradoxical sleep without any modification of slow wave sleep and wakefulness. High level of PREG-S (10 and 20 ng) increased paradoxical sleep and slow wave sleep together with an increase of delta power and a decrease of theta power during wakefulness. Dependent on the doses used, PREG-S thus can promote paradoxical sleep alone or the global propensity to fall asleep, impairing the quality of wakefulness. These results unveil a new regulation pathway for PPT neurons and strengthen the role of PREG-S in sleep-wakefulness regulation.     

Effects on sleep and wakefulness of the injection of hypocretin-1 (orexin-A) into the laterodorsal tegmental nucleus of the cat

Anatomical data demonstrate a dense projection, in the cat, from hypocretin (orexin) neurons in the hypothalamus to the laterodorsal tegmental nucleus (LDT), which is a critical pontine site that is involved in the regulation of the behavioral states of sleep and wakefulness. The present study was therefore undertaken to explore the hypocretinergic control of neurons in the LDT vis-à-vis these behavioral states. Accordingly, hypocretin-1 was microinjected into the LDT of chronic, unanesthetized cats and its effects on the percentage, latency, frequency and duration of wakefulness, quiet (non-REM) sleep and active (REM) sleep were determined. There was a significant increase in the time spent in wakefulness following the microinjection of hypocretin-1 into the LDT and a significant decrease in the time spent in active sleep. The increase in the percentage of wakefulness was due to an increase in the duration of episodes of wakefulness; the reduction in active sleep was due to a decrease in the frequency of active sleep episodes, but not in their duration. These data indicate that hypocretinergic processes in the LDT play an important role in both of the promotion of wakefulness and the suppression of active sleep.     

Pontine-wave generator activation-dependent memory processing of avoidance learning involves the dorsal hippocampus in the rat

The aim of this study was to test the hypothesis that the dorsal hippocampus plays a critical role in pontine-wave (P-wave) generator activation-dependent memory processing of two-way active avoidance (TWAA) learning. To achieve this objective, rats were given small bilateral lesions in the CA1, dentate gyrus (DG), or CA3 region of the dorsal hippocampus by microinjecting ibotenic acid. After recovery, lesioned and sham-lesioned rats were trained on a TWAA learning paradigm, allowed a 6-hr period of undisturbed sleep, and then were tested on the same TWAA paradigm. It was found that lesions in the CA3 region impaired retention of avoidance learning. Conversely, lesions in the CA1 and DG regions had no effect on TWAA learning retention. None of the groups showed any changes in the baseline sleep-wake cycle or in the acquisition of TWAA learning. All rats showed increased rapid eye movement (REM) sleep and increased REM sleep P-wave density during the subsequent 6-hr recording period. Impaired retention in the CA3 group occurred despite an increase in REM sleep and P-wave density, suggesting that during REM sleep, the P-wave generator interacts with the CA3 region of the dorsal hippocampus to aid in consolidation of TWAA learning. The results of the present study thus demonstrate that P-wave generator activation-dependent consolidation of memory requires an intact CA3 subfield of the dorsal hippocampus. The results also provide evidence that under mnemonic pressure, the dorsal hippocampus may not be involved directly in regulating the sleep-wake cycle.     

Y-maze learning in two strains of mice. Effects of instrumental and pharmacologic sleep deprivation]

Effects of instrumental and pharmacological deprivation of sleep on Y-maze learning have been studied in two inbred strains of mice (C57BR/cd/Orl and C57BL/6/Orl), having identical sleep rhythms, but mainly differing in their ability to learn. Administration of alpha-methyl-DOPA (100 mg/kg) provokes complete suppression of paradoxical sleep (PS) for 9-11 h. Injection immediately after each training session over the first 5 days caused a delay in acquisition of an active avoidance task in C57BR mice. Treated C57BL/6 mice exhibited a significant facilitation of acquisition. Similar results were obtained by instrumental deprivation of sleep for 10 h.     

Comparison of the sleep pattern throughout a protocol of chronic sleep restriction induced by two methods of paradoxical sleep deprivation

The purpose of the present study was to evaluate the sleep homeostasis of rats submitted to a protocol of chronic sleep restriction by two methods and to evaluate the sleep characteristics during the recovery period. The sleep restriction protocol was accomplished by sleep depriving rats for 18 h everyday for 21 days, using the single platform method (SPM) or the modified multiple platform method (MMPM) of paradoxical sleep (PS) deprivation. Rats were allowed to sleep for 6 h (from 10:00 to 16:00; starting 3 h after lights on) in their individual home-cages, during which their sleep was recorded. At the end of the sleep restriction protocol, rats were recorded in their home-cages for 4 days, where they could sleep freely. Both methods used to induce chronic sleep restriction were effective, in sofar as they resulted in augmented sleep time during the 6h-sleep period, with very few bouts of wakening. Although comparison between the methods did not reveal differences, sleep restriction under MMPM produced a more consistent daily rebound, mainly of paradoxical sleep, with longer episodes. These results showed distinct sleep recovery patterns, suggesting a possible role of the waking experiences (i.e. immobilization stress, social interaction) acting on sleep consolidation.     

Effect of stimulation of the nucleus reticularis gigantocellularis on the membrane potential of cat lumbar motoneurons during sleep and wakefulness

The present study was performed in order to determine the effect of electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on the membrane potential of spinal cord motoneurons during sleep and wakefulness. Accordingly, intracellular recordings were obtained from lumbar motoneurons in unanesthetized normally respiring cats during naturally occurring states of wakefulness, quiet sleep and active sleep. Electrical stimuli applied to the NRGc evoked synaptic potentials which occurred at short latency (<10ms) and did not exhibit consistent changes in their waveforms during any states of sleep or wakefulness. During wakefulness and quiet sleep, longer latency (20ms) low-amplitude hyperpolarizing potentials occasionally followed NRGc stimulation. However, during active sleep, NRGc stimulation produced,in all motoneurons, relatively large hyperpolarizing potentials that were characterized by a mean amplitude of3.5±0.4mV(mean±S.E.M.), a mean latency-to-peak of43.0±0.8ms, and an average duration of34.4±1.7ms. These potentials were capable of blocking the generation of orthodromic spikes elicited by sciatic nerve stimulation. When anodal current or chloride was passed through the recording electrode, the hyperpolarizing potentials decreased in amplitude, and in some cases their polarity was reversed. These results indicate that the active sleep-specific hyperpolarizing potentials were inhibitory postsynaptic potentials. Thus, the NRGc possesses the capability of providing a postsynaptic inhibitory drive that is directed toward lumbar motoneurons which is dependent on the occurrence of the behavioral state of active sleep. These data suggest that the NRGc may be an important link in the brainstem-spinal cord system that is responsible, during active sleep, for the postsynaptic inhibition of lumbar motoneurons.     

Effects of locus coeruleus lesions upon sleeping and waking in the rabbit

The effects of radiofrequency lesions in the region of the locus coeruleus (LC) upon sleep-waking states and behaviors were investigated in chrolically implanted New Zealand White rabbits. Polygraphic recordings were taken prior to and at 5- and 14-day intervals following lesioning. In animals exhibiting absence of paradoxical sleep and the presence of bizarre motor behavior, additional recordings were taken 30 days postlesion.

Prelesion sleep-wakefulness pattern data were comparable to those previously observed in intact rabbits, including the recently reported absence of sustained PS-related nuchal muscle atonia. Lesions histologically localized to the area of the locus coeruleus were of two types, i.e., those effecting bilateral destruction of≥ 80% (n= 11)or30–50% (n= 11) of the LC. A transient period of inactivity was present immediately following lesioning, but by two weeks postlesion animals had generally regained normal waking behavioral and physiological functioning, e.g., eating, drinking and grooming behaviors had returned and respiration, micturition and general urological functioning were normal. The more extensive LC lesions were followed by increases in the proportion of total recording time spent in wakefulness, but primarily in quiet rather than active wakefulness.

Sleep was fragmented by phasic muscular activation in proportion to the amount of LC destroyed. In animals with the most extensive lesions, slow wave sleep was interrupted by brief, abrupt episodes of twitching, and eposides of marked phasic muscular activation, often violent in nature, occurred following periods of slow wave sleep. The postlesion occurrence of PS was inversely related to the degree of LC destruction and, accordingly, to the presence of episodes of phasic motor activation.

These results did not confirm earlier in other species imlicating the LC in urogenital functioning and respiration, but do corroborate previous findings indicating that neural elements in the LC regions are essential to the integrity of sleep and are especially important to the control of motor mechanisms during sleep.     

Vigilance states in a parkinsonian model, the MPTP mouse

Sleep disturbances and vigilance disorders are frequently observed in Parkinson's disease. Despite the fact that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse is one of the best-known animal models of Parkinson's disease, sleep analysis has never previously been performed in this system. In the present study, we explored sleep-wakefulness cycles in MPTP-treated mice and compared the results to data from untreated mice. MPTP (25 mg/kg) was injected daily for 5 days. After recovery, polysomnography was recorded over 48 h. Dopaminergic lesions of the substantia nigra and striata were evaluated using immunohistochemical markers. Immunohistochemical analysis showed a loss of dopaminergic neurons in MPTP mice. Compared with controls, MPTP-treated mice presented changes in sleep architecture throughout the nycthemeral period, with longer wakefulness and paradoxical sleep episodes and an increase in the amount of paradoxical sleep. We observed changes in sleep architecture in MPTP-treated mice, compared with saline-treated mice. MPTP mice show more consolidated vigilance states with higher amount of paradoxical sleep than controls. Although the MPTP-treated mouse is not a good model of sleep disturbances in PD, our results suggest that it could be a good pharmacological model for studying the effects of dopaminergic treatments on animal sleep-wakefulness cycles.     

Behavior-dependent modulation of hippocampal EEG activity by the selective norepinephrine reuptake inhibitor reboxetine in rats

Both active wakefulness and rapid eye movement sleep (REM) give rise to rhythmic synchronized hippocampal field oscillations, known as theta activity. Antidepressant drugs, including norepinephrine re-uptake inhibitors are proven to diminish REM sleep, and REM sleep-related hippocampal theta oscillation. Since reboxetine, a highly selective norepinephrine re-uptake inhibitor has been shown to block REM sleep, but induce or facilitate hippocampal theta activity in anesthetized rats, the current study investigated the effects of reboxetine on stage- and behavior dependent theta activity. Polysomnographic recordings, which included hippocampal field potentials at the hippocampal fissure, were carried out in rats for 8 h during the light phase of the circadian cycle. Theta rhythm was analyzed during three different behavioral conditions: REM sleep, during motor activity in a familiar environment, and during exploration in a novel environment. We found that, compared with REM sleep, theta power was relatively low during periods of active wakefulness when the animal was in the familiar home cage, but considerably increased during exploration in a novel environment. Reboxetine suppressed sleep and thus abolished REM sleep-related hippocampal theta rhythm, attenuated theta in the familiar environment, and significantly enhanced theta oscillations associated with exploratory behavior. Our findings demonstrate a state- and behavior-dependent modulation of hippocampal theta activity by reboxetine, providing further evidence for a prominent role of norepinephrine in arousal and focused or selective attention.     

Computer graphics analysis of sleep-wakefulness state changes after pontine lesions

The average EEG amplitude, average EMG amplitude and PGO spike rate per one minute epoch were measured for 3 days before and 21 days after pontine lesions in the cat. A trivariate computer graphics display of one baseline day's data (of 1350 epochs) revealed three major clusters of points that were automatically sorted by cluster analysis and corresponded to wakefulness, slow wave sleep and paradoxical sleep. Following combined medial-lateral caudal pontine lesions, the cluster of points that corresponded to the state of paradoxical sleep was absent. Two clusters were still evident and corresponded to wakefulness and slow wave sleep, which was characterized by higher than normal EMG amplitude and PGO spike rate. Whereas medial caudal pontine lesions alone did not reproduce these effects, lateral caudal pontine lesions did. These results suggest that cells and/or fibers located within the lateral tegmental field rather than those within the medial gigantocellular tegmental field of the pons are most important for the generation of the cluster of events that characterize paradoxical sleep.     

Effect of lighting on maturation of neural elements controlling biorhythm of sleep, wakefulness and paradoxical sleep in rats

Biorhythm of sleep, wakefulness and paradoxical sleep was studied in unanesthetized, freely moving, female rats. A concentric bipolar stainless steel electrode for EEG recording was placed in the dorsal hippocampus and monopolar EEG recording electrodes were placed in the formal cortex. One week after surgery, and the resumption of consecutive 4 days estrous cycles, EEG patterns were recorded for 7 consecutive days.Female rats subjected to light and dark schedule (LD) during the period of gestation and through puberty exhibited a diurnal rhythm of sleep, and paradoxical sleep; a circadian rhythm with peaks of sleep during the light phase. When these rats were transferred from LD to continous illumination (CI), circadian rhythm was annihilated and indeed all rhythms disappeared. It seems likely that light serves as synchronizer or oscillator for regulation of circadian rhythm of sleep, wakefulness and paradoxical sleep. However, in female rats subjected to CI during the period of gestation and puberty, light apparently does not serve as synchronizer or oscillator for the regulation of circadian rhythm. Further, these rats exhibit a nocturnal rhythm (12 h shift of acrophase of circadian rhythm of sleep and parodoxical sleep from rats born and reared in LD) of sleep, and paradoxical sleep; a circadian rhythm with peaks of sleep during midnight.The evidence illustrates the nature of oscillatory phenomena controlling circadian rhythm of sleep, wakefulness and paradoxical sleep in rats.