Effects of the selective alpha 1-adrenoceptor blocker prazosin on EEG sleep and waking stages in the rat

In order to gain a better understanding of the role of the noradrenergic system in the control of the EEG sleep-waking stages, the effects of the selective alpha 1-antagonist prazosin was investigated in the rat. Oral doses of prazosin (0.1-10 mg/kg) were administered that have been shown to enter the brain. EEG sleep and waking stages were recorded either during 8 h after drug administration at 8.00 in the morning or during 48 h after drug administration at 16.00 in the afternoon. It was found that prazosin at doses of 0.1-10 mg/kg shortened quiet waking. Starting at 1 mg/kg paradoxical sleep (PS) was shortened and, most interestingly, active waking and slow wave sleep (SWS) were prolonged. PS spindles and dozing were shortened after a latency of some hours during the 48-hour experiment. However, during the 8-hour experiment PS spindles were prolonged at 0.32 and 1 mg/kg. These data suggest that in the rat alpha 1-adrenoceptor inhibition in the brain allows the occurrence of active waking and SWS and suppresses PS.     

Acute and long-term effects of the 5-HT2 receptor antagonist ritanserin on EEG power spectra,motor activity,and sleep: changes at the light-dark phase shift

Parallel effects of a single injection of the 5-HT(2) receptor antagonist ritanserin on EEG power spectra, sleep and motor activity were measured for a 20-h period in freely moving Sprague-Dawley rats. Ritanserin (0.3 mg/kg, i.p.), administered at light onset (passive phase), caused an immediate transient increase in the EEG power density in the low frequency range (0.25-6 Hz, mainly delta activity) and a depression in the high frequency range (27-30 Hz) accompanied by a decrease in vigilance and light slow wave sleep (SWS-1), intermediate stage of sleep and increase in deep slow wave sleep (SWS-2) compared to control treatment. All these effects were over 8 h after the injection. Twelve hours after the injection, at dark onset (active phase), there was a marked increase in vigilance and motor activity and decrease in SWS-1 and spindle frequency activity in the control animals, but all these changes were diminished by ritanserin treatment. These effects resulted in a significant relative increase in the intermediate band (peak: 12-15 Hz) of the EEG power spectra and thus, a relative increase in thalamo-cortical synchronization caused by ritanserin at dark onset. Because ritanserin is a selective 5-HT(2) receptor antagonist, we conclude that under physiological conditions serotonin increases EEG desynchronization and produces an increase in vigilance level and motor activity by tonic activation of 5-HT(2) receptors. This regulatory mechanism plays an important role in the waking process, and the appearances of its effects in the light and dark phase are markedly different.     

A large scale, high resolution, automated system for rat sleep staging. I. Methodology and technical aspects

An automatic rat sleep classification system is described which records and analyses bioelectrical signals from 32 rats over extended periods of time. At present this system is used routinely for the screening of drug effects on sleep. The analysis is based on 3 signals, the parieto-occipital EEG, nuchal EMG and a movement indicator signal. The on-line analysis is done per epoch of 2 sec and involves power spectral analysis of the EEG and rectification and integration of the EMG and movement signals. The automatic sleep staging into 6 stages (active and quiet waking; quiet, deep, pre-REM and REM sleep) is performed off-line. Parameters derived from a discriminant analysis of visually scored tracings of individual rats constitute the basis for the automatic scoring procedure. The movement index is used to discriminate between active and quiet waking, while the use of the EMG level improves the separation of waking and REM sleep. After the construction of hypnograms from these computer scorings a set of parameters can be extracted which characterizes the sleep-waking behavior of each individual rat. These parameters are then used to compare statistically the 2-4 treatment groups which make up each experiment of 32 rats. Experimental validation of the system is reported in an accompanying paper.     

Age-related changes in sleep-wake rhythm in dog

To investigate a sleep-wake rhythm in aged dogs, a radio-telemetry monitoring was carried out for 24 h. Electrodes and telemetry device were surgically implanted in four aged dogs (16-18 years old) and four young dogs (3-4 years old). Electroencephalogram (EEG), electromyogram (EMG) and electrocardiogram (ECG) were recorded simultaneously as parameters to determine vigilance states and an autonomic nervous function. Wakefulness, slow wave sleep (SWS) and paradoxical sleep (PS) were identified according to the EEG and EMG pattern. We also examined whether absolute powers and the low frequency-to-high frequency ratio (LF/HF) derived from the heart rate variability power spectrum could detect shifts in autonomic balance correlated with aging. The aged dogs showed a marked reduction of PS and a fragmentation of wakefulness in the daytime and a sleep disruption in the night. The pattern of 24 h sleep and waking was dramatically altered in the aged dog. It was characterized by an increase in the total amount of time spent in SWS during the daytime followed by an increasing of time spent in wakefulness during the night. Furthermore, LF/HF ratio showed a very low amplitude of variance throughout the day in the aged dog. These results suggest that the aged dog is a useful model to investigate sleep disorders in human such as daytime drowsiness, difficulties in sleep maintenance. The abnormality in sleep-wake cycle might be reflected by the altered autonomic balance in the aged dogs.     

Differential c-Fos expression in cholinergic, monoaminergic, and GABAergic cell groups of the pontomesencephalic tegmentum after paradoxical sleep deprivation and recovery.

Multiple lines of evidence indicate that neurons within the pontomesencephalic tegmentum are critically involved in the generation of paradoxical sleep (PS). From single-unit recording studies, evidence suggests that unidentified but "possibly" cholinergic tegmental neurons discharge at higher rates during PS than during slow wave sleep or even waking and would thus play an active role, whereas "presumed" monoaminergic neurons cease firing during PS and would thus play a permissive role in PS generation. In the present study performed on rats, c-Fos immunostaining was used as a reflection of neuronal activity and combined with immunostaining for choline acetyltransferase (ChAT), serotonin (Ser), tyrosine hydroxylase (TH), or glutamic acid decarboxylase (GAD) for immunohistochemical identification of active neurons during PS recovery ( approximately 28% of recording time) as compared with PS deprivation (0%) and PS control (approximately 15%) conditions. With PS recovery, there was a significant increase in ChAT+/c-Fos+ cells, a significant decrease in Ser+/c-Fos+ and TH+/c-Fos+ cells, and a significant increase in GAD+/c-Fos+ cells. Across conditions, the percent PS was correlated positively with tegmental cholinergic c-Fos+ cells, negatively with raphe serotonergic and locus coeruleus noradrenergic c-Fos+ cells, and positively with codistributed and neighboring GABAergic c-Fos+ cells. These results support the hypothesis that cholinergic neurons are active, whereas monoaminergic neurons are inactive during PS. They moreover indicate that GABAergic neurons are active during PS and could thus be responsible for inhibiting neighboring monoaminergic neurons that may be essential in the generation of PS.     

Angiotensin II protects cultured midbrain dopaminergic neurons against rotenone-induced cell death

In humans, EEG power in the theta frequency band (5-8 Hz) during quiet waking increases during sleep deprivation (SD), and predicts the subsequent homeostatic increase of sleep slow-wave activity (SWA; EEG power between 0.5 and 4.0 Hz). These findings indicate that theta power in waking is an EEG variable, which reflects the rise in sleep propensity. In rodents, a number of short sleep attempts, as well as SWA in the waking EEG increase in the course of SD, but neither variable predicts the subsequent homeostatic increase of EEG SWA during recovery sleep. To investigate whether there is an EEG marker for sleep propensity also in rodents, the EEG of the rat was recorded during 6 h SD in the first half of the light period (SDL, n = 7). During SDL, power of the waking EEG showed an increase in the delta (1.5-4 Hz) and low theta (5-6.5 Hz) band. Based on the neck muscle EMG, wakefulness was subdivided into active (high EMG activity) and quiet (low EMG activity) waking. During quiet waking, the theta peak occurred at 5.5 Hz, the frequency at which the increase of EEG power during SD was most pronounced. This increase was due to higher amplitude of theta waves, while wave incidence (frequency) was unchanged. Correlation analysis showed that the rise in EEG power in the 5-7 Hz band during SD predicted the subsequent enhancement of SWA in non-rapid eye movement sleep. The analysis of data of a further batch of rats which were sleep deprived for 6 h after dark onset (SDD, n = 7) revealed a significant increase in theta-wave amplitude during the SD and a tendency for a similar, positive correlation between the increase of theta power (5-7 Hz) and subsequent SWA. The results indicate that in rats, as in humans, a specific waking EEG frequency, i.e., theta power in quiet waking is a marker of sleep propensity.     

Increased waking as well as increased synchronization following administration of selective 5-HT uptake inhibitors to rats

Sleep and waking stages and EEG power spectra were investigated in rats following saline injections and injection of 10 and 20 mg/kg zimeldine or 10 and 20 mg/kg alaproclate, both selective 5-HT reuptake inhibitors. Following zimeldine there was a biphasic effect on sleep and waking, waking being increased during the first 2 1/2 h of recording, while slow wave sleep (SWS), in particular highly synchronized SWS-2 with high slow wave activity, was increased during the second 2 1/2 h recording period. Analysis of EEG power spectra indicated that the amount of synchronized slow wave activity was also increased within the sleep that occurred during the waking-dominated initial 2 1/2 h period. These data suggest simultaneous appearance of increased waking and increased synchronization following general serotonergic stimulation. They are interpreted as due to effects on different regions of the serotonergic system or on different serotonergic receptors. Consistent with earlier findings, zimeldine also suppressed rapid eye movement (REM) sleep. Following alaproclate, a clear waking effect was present, but only a weak synchronizing effect was seen. This is consistent with data on regional differences in uptake inhibition for zimeldine and alaproclate. Alaproclate also reduced REM sleep. Zimeldine or alaproclate was also administered to rats that had reduced sleep following pretreatment with a moderate dose of parachlorophenylalanine (PCPA). None of the drugs increased waking any further, but the PCPA-pretreated animals that received zimeldine had increased SWS-2, indicating that the SWS-2 increase following zimeldine alone was not a rebound effect.     

Hypoprolactinemic rats under conditions of constant darkness or constant light. Effects on the sleep-wake cycle, cerebral temperature and sulfatoxymelatonin levels.

In genetic hypoprolactinemic rats under light-dark (LD) conditions, the circadian rhythms of slow-wave (SWS) and paradoxical (PS) sleep display an alteration of their phase relationship. The aim of our study was to investigate the effects of constant darkness (DD) or constant light (LL) on the daily distribution and amounts of sleep-wake stages, cerebral temperature and concentrations of the urinary melatonin metabolite, 6-sulfatoxymelatonin, in prolactin-deficient rats. After 3 weeks of DD, the SWS period was 24 h 8+/-6 min and the acrophase occurred at 15:44+/-1:35, while for PS, the period was more stable than during LD (24 h 10+/-8 min vs. 24 h 55+/-43 min) and the acrophase occurred at 16:44+/-1:54. Under LL conditions, circadian sleep rhythms persisted during the first 3 days, then completely disappeared during the third week, to be replaced by ultradian rhythms (period of 4-6 h). Time-series analysis showed that the two sleep states became synchronous as early as the second day under constant conditions. The total amount of PS was increased under both conditions (LL and DD) at the expense of duration of waking. Under LD and constant conditions, the pattern of changes in cerebral temperature was similar to that for wakefulness (W). Sulfatoxymelatonin was rhythmically secreted under both LD and DD conditions, whereas, under LL conditions, its rhythm was abolished. The results show that, in IPL rats in the absence of a zeitgeber, the PS and SWS rhythms recover a synchronous phase relationship and PS amounts are increased.     

Extracellular serotonin variations during vigilance states in the preoptic area of rats: a microdialysis study

Numerous studies have shown that serotonergic transmission decreases from waking (W) to slow wave sleep (SWS) to paradoxical sleep (PS), suggesting an active role of serotonin (5-HT) in W but not in sleep. Conversely, the inhibition of 5-HT activity produces insomnia. This insomnia can be reversed by injections of 5-hydroxytryptophan in the preoptic area (POA), suggesting that 5-HT is necessary in this cerebral structure for sleep. Using microdialysis, we studied, 5-HT variations in the POA of rats in relation to vigilance states. 5-HT levels were higher during W than during during SWS and PS. 5-HT increased just before the rats fell asleep and then decreased during sleep. A decreased 5-HT transmission was also observed from SWS to PS. These data document a positive correlation between 5-HT levels in POA and wakefulness. Moreover, these observations are in favour of a permissive role of 5-HT in the POA during PS. A comparison between the POA and the prefrontal cortex in the sleep–wake cycle is discussed.     

Value of the sleep diary in the study of vigilance dis

This study presents an easy and practical subjective method for evaluating vigilance disorders: the sleep diary. We used it in hypersomnia and deficits of waking. Sleep diaries were filled in by 10 control and 22 hypersomniac subjects. Twenty-four hour polyhypnographic recording allowed the classification of hypersomnia as 13 narcolepsies, 9 hypersomnias with a prevalence of PS, 2 'harmonious' hypersomnias and 1 waking deficit. The sleep diary data (amount of nocturnal sleep and diurnal sleep onset and vigilance decrease) were compared with polygraphic results. According to the diary data, 3 groups of hypersomnia appeared with regard to the time at which sleep onset occurred. The first group presented an increase of sleep onsets at 2 p.m. In the second group, almost exclusively composed of narcoleptic subjects, sleep onsets occurred every 2 h and in the third group they were distributed throughout the day. These results suggest different physiological mechanisms for these 3 groups of hypersomnia. Finally, the sleep diary seems to be an easy and cheap method of evaluating vigilance disorders in hypersomniac subjects during their everyday life.     

GABAergic neurons intermingled with orexin and MCH neurons in the lateral hypothalamus discharge maximally during sleep

The lateral hypothalamus (LH), where wake‐active orexin (Orx)‐containing neurons are located, has been considered a waking center. Yet, melanin‐concentrating hormone (MCH)‐containing neurons are codistributed therein with Orx neurons and, in contrast to them, are active during sleep, not waking. In the present study employing juxtacellular recording and labeling of neurons with Neurobiotin (Nb) in naturally sleeping–waking head‐fixed rats, we identified another population of intermingled sleep‐active cells, which do not contain MCH (or Orx), but utilize γ‐aminobutyric acid (GABA) as a neurotransmitter. The ‘sleep‐max’ active neurons represented 53% of Nb‐labeled MCH‐(and Orx) immunonegative (?) cells recorded in the LH. For identification of their neurotransmitter, Nb‐labeled varicosities of the Nb‐labeled/MCH? neurons were sought within sections adjacent to the Nb‐labeled soma and immunostained for the vesicular transporter for GABA (VGAT) or for glutamate. A small proportion of sleep‐max Nb+/MCH? neurons (19%) discharged maximally during slow‐wave sleep (called ‘S‐max’) in positive correlation with delta electroencephalogram activity, and from VGAT staining of Nb‐labeled varicosities appeared to be GABAergic. The vast proportion of sleep‐max Nb+/MCH? neurons (81%) discharged maximally during paradoxical sleep (PS, called ‘P‐max’) in negative correlation with electromyogram amplitude, and from Nb‐labeled varicosities also appeared to be predominantly GABAergic. Given their discharge profiles across the sleep–wake cycle, P‐max together with S‐max GABAergic neurons could thus serve to inhibit other neurons of the arousal systems, including local Orx neurons in the LH. They could accordingly dampen arousal with muscle tone and promote sleep, including PS with muscle atonia.     

Classical sleep stages and the spectral content of the EEG signal

Polygraphic sleep recordings during 12 nights in 5 healthy volunteers were classified manually into waking and the various sleep stages. The smoothed power spectra of EEG signal segments defined as waking or one of the sleep stages were calculated via segmentation of the EEG signal, using the autoregressive model, and time-dependent fuzzy clustering. The spectra were derived from the prediction coefficients of the segments. The relative power in the delta frequency band was found to increase monotonically with increasing depth of sleep, together with a parallel decrease in the alpha relative power. In most cases alpha relative power had a small peak during REM sleep, and on average the relative power in the sigma frequency band during REM sleep was smaller than the beta relative power. The power spectra from subjects with no waking alpha differed from those of subjects with abundant waking alpha mostly in the relative spectral content of stages 1 and REM. The significance of these findings is discussed in relation to future standardisation of automatic analysis of sleep recordings.     

Activity of serotonin-containing neurons in nucleus raphe magnus in freely moving cats

Serotonergic neurons were recorded in the nucleus raphe magnus in freely moving cats and were initially identified on-line by their characteristic slow and regular spontaneous activity during quiet waking (3.42 +/- 0.33 spikes/s; mean +/- SE). Discharge rates of these serotonergic neurons were highest during active waking (4.49 +/- 0.40 spikes/s), intermediate during slow-wave sleep (middle: 2.14 +/- 0.23 spikes/s), and lowest during REM sleep (0.20 +/- 0.03 spikes/s). Although these cells fired at a rate 31.3% higher during active waking than during quiet waking, their activity displayed no correlation with phasic elevations of the nuchal EMG or overt body movements. In addition, no relationship was observed between the activity of these neurons during slow-wave sleep and the occurrence of sleep spindles in the cortical EEG or pontogeniculooccipital waves recorded from the lateral geniculate nucleus. Serotonergic neurons of nucleus raphe magnus were also relatively unresponsive to phasic auditory and visual stimuli, with about half of the cells examined showing weak excitatory responses. These neurons did respond, however, to the administration of a small dose of the serotonin specific agonist, 5-methoxy-N,N-dimethyltryptamine (250 micrograms/kg, i.m.) with a mean decrease in unit activity of 73.6 +/- 4.5%. The results of this study are compared with those previously reported for serotonergic neurons in the dorsal raphe nucleus, nucleus centralis superior, and nucleus raphe pallidus of freely moving cats.     

Sleep/waking effects following intrathecal administration of the 5-HT1A agonist 8-OH-DPAT alone and in combination with the putative 5-HT1A antagonist NAN-190 in rats

Sleep, waking, and EEG power spectra were investigated in rats after intrathecal (IT) administration of a 5-HT_1A agonist and a 5-HT_1A antagonist. Total slow wave sleep (TSWS) was increased and waking was decreased over the 8-h recording period after the 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (38 nmol). Within TSWS, SWS1 was unchanged while SWS-2 tended to be increased. The 5-HT_1A antagonist 1-[2-Methoxyphenyl)-4-(4-(2-phthalimido)-butyl]piperazine hydrobomide (NAN-190) did not change and sleep/waking stages. Combined treatment with 8-OH-DPAT and NAN-190 increased variance. Following the combination, sleep and waking were not significantly different from control. SWS-2 tended to be reduced compared to the effect of 8-OH-DPAT alone. There were no systematic changes in neither waking nor TSWS fronto-frontal or fronto-parietal EEG power spectrum after any of the treatments, indicating that sleep quality was not changed. The results confirm earlier data suggesting that in the spinal cord, stimulation of 5-HT1A receptors have a dampening effect on transmission of sensory information, leading to deactivation and thereby increased sleep tendency. The reason why the 8-OH-DPAT effect was not clearly antagonized by the putative 5-HT1A antagonist NAN-190, may be due to the generally weak antagonistic and also partial agonistic effect of NAN-190 as reported in the literature.     

Spike-wave discharges and sleep-wake states in rats with absence epilepsy.

The occurrence of spike-wave discharges was studied in relation to the daily fluctuations of vigilance level in rats. Eight rats of the WAG/Rij strain, an animal model for idiopathic generalized epilepsy of the absence type, which were equipped with cortical EEG and nuchal EMG electrodes, served as subjects. It was found that spike-wave discharges predominantly occur during light slow wave sleep and passive wakefulness. REM sleep, active wakefulness, and deep slow wave sleep are less susceptible to the occurrence of spike-wave discharges. Finally, spike-wave discharges tend to prevail in transitional states. A crucial role for the degree of stability of the level of vigilance in the genesis of absence seizures is suggested.     

Sleep effects following intrathecal administration of the 5-HT1A agonist 8-OH-DPAT and the NMDA antagonist AP-5 in rats

The modulating effect of an intrathecally (i.t.) administered 5-HT_1A agonist and an NMDA antagonist on sleep, waking and EEG power spectra was investigated in rats. The 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (38 nmol) increased total slow wave sleep (TSWS) and decreased waking over the 8 h recording period. The TSWS increase was mostly due to an increase in SWS1. Sleep latency to SWS1 was also reduced. The NMDA antagonist dl-2-amino 5-phosphonovaleric acid (AP-5) (31.5 nmol) reduced waking. SWS1 was increased, but TSWS was not changed. An increase in REM sleep was seen during the last part of the recording. Combined treatment with 8-OH-DPAT and AP-5 reduced waking and increasd TSWSS. No change in REM sleep was seen. There were no systematic changes in either waking, TSWS or REM fronto-frontal or fronto-parietal EEG power spectrum after any of the treatments. The results suggest that in the spinal cord stimulation of 5-HT_1A receptors have a dampening effect on transmission of sensory information, leading to deactivation and thereby increased possibilities for sleep induction. Blockade of the NMDA receptors may also lead to a small dampening of sensory transmission with similar consequences.     

Waking EEG power spectra in the rat: correlations with training performance

Adult rats chronically implanted with supradural electrodes were telemetrically EEG recorded during a baseline session, a training session for a two-way active avoidance task, and a retention session. Rats were assigned to a fast learning (FL), slow learning (SL) and non learning (NL) group if they achieved criterion during the training session, the retention session, or in neither session. High-resolution EEG analyses indicated that intergroup differences were present in the low frequency range of waking baseline power spectra. Moreover, baseline delta emissions directly correlated with freezings, and inversely correlated with avoidances, while emissions at 7-10 Hz directly correlated with avoidances and inversely correlated with freezings. Interestingly, during the first training period, waking delta emission selectively increased in FL rats in concomitance with a marked performance improvement; instead, SL and NL rats displayed increments at 7-9 Hz. In addition, freezings scored during the first two training periods directly correlated with post-training waking emission at 2 Hz, and inversely correlated with emission at 7-10 Hz. Conversely, escapes and avoidances directly correlated with waking emission at 7-10 Hz. The data indicate that (i) waking baseline power spectra differ among behavioral groups, and correlate with behavioral performance the following day; (ii) selective modifications of waking power spectra occur in each behavioral group during training; and (iii) behavioral responses during training correlate with post-training waking power spectra. Notably, the delta increment selectively occurring in training FL rats is assumed to reflect online memory processing leading to better performance. The latter observation supports the primary involvement of delta waves in learning.     

Sleep and wakefulness in the southern sea lion

We recorded an electroencephalogram from the two hemispheres, a neck musculature electromyogram, an electrooculogram, and respiratory acts during sleep and wakefulness on land in three 1-year-old sea lion females for 3 or 4 consecutive days. On average active wakefulness (AW) occupied 20.4+/-2.0% of the 24-h period; quiet wakefulness (QW) 54.9+/-2.5%; slow wave sleep (SWS) 15.0+/-2.5% and paradoxical sleep (PS) 9.7+/-2.0%. Between 30 and 50% (average 39.1+/-3.4%) of total sleep time was spent in PS. From 8 to 31 episodes of PS were recorded per day (average 17+/-6 per day), with the longest episode lasting 20 min (average 5.6+/-0.5 min). Episodes of interhemispheric EEG asymmetry accounted for 5.5+/-1.3% of total SWS time. Respiratory pauses in these animals varied in QW between 4 and 36 s (average 15.7+/-0.4 s), in SWS between 11 and 37 s (20.9+/-0.6 s) and in PS between 2 and 69 s (15.0+/-1.5 s). AW, QW, SWS and PS were approximately equally distributed between light (07:00-19:00) and dark time (19:00-07:00). The low amount of SWS with interhemispheric EEG asymmetry, the high proportion of PS in total sleep time and the nearly even distribution of sleep and wakefulness over the 24-h period could be both species-specific features and/or ontogenetic characteristics of the animals studied.     

Brain extracellular glucose assessed by voltammetry throughout the rat sleep-wake cycle

In the present study, cortical extracellular levels of glucose were monitored for the first time throughout the sleep-wake states of the freely moving rat. For this purpose, polygraphic recordings (electroencephalogram of the fronto-occipital cortices and electromyogram of the neck muscles) were achieved in combination with differential normal pulse voltammetry (DNPV) using a specific glucose sensor. Data obtained reveal that the basal extracellular glucose concentration in the conscious rat is 0.59 +/- 0.3 m M while under chloral hydrate anaesthesia (0.4 g/kg, i.p.) it increases up to 180% of its basal concentration. Regarding the sleep-wake cycle, the existence of spontaneous significant variations in the mean glucose level during slow-wave sleep (SWS = +13%) and paradoxical sleep (PS = -11%) compared with the waking state (100%) is also reported. It is to be noticed that during long periods of active waking, glucose level tends towards a decrease that becomes significant after 15 min (active waking = -32%). On the contrary, during long episodes of slow-wave sleep, it tends towards an increase which becomes significant after 12 min (SWS = +28%). It is suggested that voltammetric techniques using enzymatic biosensors are useful tools allowing direct glucose measurements in the freely moving animal. On the whole, paradoxical sleep is pointed out as a state highly dependent on the availability of energy and slow-wave sleep as a period of energy saving.     

Lateral geniculate spikes, muscle atonia and startle response elicited by auditory stimuli as a function of stimulus parameters and arousal state

We have investigated the motor and ponto-geniculo-occipital (PGO) wave response to startle eliciting stimuli in the unanesthetized cat. We found that the amplitude of the PGO spike recorded in the lateral geniculate nucleus (LGN) increases monotonically with increasing intensities of auditory stimuli. In contrast, the motor response to low intensity (less than 75 dB) stimuli is characterized by electromyographic (EMG) suppression, while at higher intensities an EMG excitation is superimposed on this suppression. Thus PGO elicitation is accompanied by EMG suppression at low intensities and by a net EMG excitation at high intensities. While the amplitude of the auditory elicited PGO response is a graded function of stimulus intensity, somatic stimuli tend to elicit the PGO response in all-or-none fashion. Both the motor and PGO responses to sensory stimulation change with behavioral state. The EMG suppression by auditory stimulation increases in duration during the transition to rapid eye movement (REM) sleep. Elicited PGO amplitude is highest in transitional sleep, lower in quiet waking and REM sleep and lowest in active waking. Prepulse inhibition of PGO spikes is greatly attenuated during transitional and REM sleep. We hypothesize the existence of 3 phasic response systems, a motor suppression system, a motor excitation (startle) system and a PGO elicitation system. While these systems are triggered concurrently by intense phasic stimuli in waking, they are modulated independently by stimulus intensity and behavioral state, and have different rates of habituation. These systems act in concert to produce behavioral responses to sudden onset stimuli.