Biochemical monitoring of the treatment in paediatric patients with mitochondrial disease

STUDY OBJECTIVES: In this study, we test the hypothesis that when REM-state activation (which impinges upon all lateral geniculate nucleus laminae irrespective of stimulating eye) is deprived, the monocular segment (MS) that is cut off from visual input and also deprived of REM-state activation will exhibit smaller cells, owing to the loss of extrinsic as well as intrinsic activation. DESIGN: We carried out a study comparing soma sizes in the MSs of kittens subjected to monocular deprivation (MD) + REM deprivation (RD) to two age-matched nonRD groups, MD ONLYs and MD MOMS (MD kittens living in their home cages). MEASUREMENTS AND RESULTS: Perikaryal outlines of 100 cells in each of the bilateral MSs were measured. As predicted, mean cell size in the MS connected to the patched eye of MD + RD kittens, but in neither of the control groups, was significantly smaller than in the MS afferented by the nonpatched eye. One-way ANOVAs comparing MS cell-size means from the same sides across groups were also significant, but the two MSs showed different results on post hoc tests. The ordering of MS cell-size means correlated significantly with a measure that aggregates the sources of activation reaching a particular MS and their durations. CONCLUSIONS: These results reveal that removal of REM-state activation during CNS development amplifies the plasticity processes generated when normal visual afferentation to central visual areas is interrupted. Our findings in the MS of the LGN indicate that during the usual operation of REM sleep, central visual-sensory sites receive intrinsic activation that, in the visual system, is additive and complementary to the stimulation obtained from extrinsic sources. In the course of early development, normative symmetrical activation of central visual areas during REM sleep may counterbalance plasticity changes caused either by absent or aberrant sensory stimulation.     

Monotremes and the evolution of rapid eye movement sleep

Early studies of the echidna led to the conclusion that this monotreme did not have rapid eye movement (REM) sleep. Because the monotremes had diverged from the placental and marsupial lines very early in mammalian evolution, this finding was used to support the hypothesis that REM sleep evolved after the start of the mammalian line. The current paper summarizes our recent work on sleep in the echidna and platypus and leads to a very different interpretation. By using neuronal recording from mesopontine regions in the echidna, we found that despite the presence of a high-voltage cortical electroencephalogram (EEG), brainstem units fire in irregular bursts intermediate in intensity between the regular non-REM sleep pattern and the highly irregular REM sleep pattern seen in placentals. Thus the echidna displays brainstem activation during sleep with high-voltage cortical EEG. This work encouraged us to do the first study of sleep, to our knowledge, in the platypus. In the platypus we saw sleep with vigorous rapid eye, bill and head twitching, identical in behaviour to that which defines REM sleep in placental mammals. Recording of the EEG in the platypus during natural sleep and waking states revealed that it had moderate and high-voltage cortical EEGs during this REM sleep state. The platypus not only has REM sleep, but it had more of it than any other animal. The lack of EEG voltage reduction during REM sleep in the platypus, and during the REM sleep-like state of the echidna, has some similarity to the sleep seen in neonatal sleep in placentals. The very high amounts of REM sleep seen in the platypus also fit with the increased REM sleep duration seen in altricial mammals. Our findings suggest that REM sleep originated earlier in mammalian evolution than had previously been thought and is consistent with the hypothesis that REM sleep, or a precursor state with aspects of REM sleep, may have had its origin in reptilian species.     

The effect of age on the reversibility of cellular atrophy in the LGN of the cat following monocular deprivation: a test of two hypotheses about cell growth

Monocular closure soon after birth is known to reduce the growth of the deprived cells in the LGN provided that there are competing cells with normal input. When the closed eye was opened and the open eye closed after three of six weeks of monocular closure, the originally deprived cells in the LGN were able to recover their normal size. However, it was found that after 14 weeks of monocular closure there was no recovery. The ability of the initially closed eye to excite cells in the visual cortex is known to depend on the age when eye closure is reversed in a similar manner. Thus the growth of cells in the LGN is correlated with the possession of effective synapses upon cortical cells. This result is compatible with the possession of effective synapses upon cortical cells. This result is compatible with the hypothesis that competition occurs at the cortical level. It is argued that the alternative hypothesis of competition within the LGN predicts reversibility at any age. In some kittens, the closed eye was opened and the opposite optic nerve crushed. Some evidence was then found of structural recovery even after 14 weeks of deprivation. The hypothesis of cortical competition predicts functional recovery in such kittens, but this remains to be tested.     

Changes in EEG power density during sleep laboratory adaptation

First- and second-night effects on the electroencephalogram (EEG) were investigated by means of polygraphic sleep recordings and all-night spectral analysis. Eighteen normal subjects were studied for three consecutive nights in a hospital sleep laboratory. Visual sleep scoring showed that there was a first-night effect in normal subjects similar to that reported previously [increased wakefulness; decreased total sleep time, sleep efficiency, and rapid eye movement (REM) sleep]. Spectral analysis of the sleep EEG revealed important changes, most of which occurred in REM sleep. Increased delta, theta, and beta1 power densities accompanied by decreased mean frequency were seen in REM sleep in the second night. On the basis of REM sleep deprivation results previously published, our data suggest that the second night could be affected by partial REM sleep deprivation that occurred in the first night. Delta and theta power density values decreased in the first non-rapid eye movement episode of nights 1 and 2; this could result from increased REM sleep pressure. The overall consistency of spectral data in the first and second night with REM sleep findings derived from visual scoring in the first night lends further support to this hypothesis. The sleep disturbance experienced during the first night in a sleep laboratory may be a useful and valid model of transient insomnia. Therefore, we conclude that data from all nights recorded should be included in assessing a subject's sleep.     

Differences in sleep variables, blood adenosine, and body temperature between hypothyroid and euthyroid rats before and after REM sleep deprivation

Sleep deprivation causes an increase in energy expenditure in animals. Thyroid gland function has been related to metabolic function, and this may be compromised in sleep manipulations. The objectives of the present study were the following: 1) to develop a model of hypothyroid rats by surgical removal of thyroid glands without extirpation of the parathyroid; 2) to observe the sleep architecture in euthyroid (Etx) and hypothyroid (Htx) rats, both before and after rapid eye movement (REM) sleep deprivation (96 hours); 3) to challenge both groups (i.e. Etx and Htx) with REM sleep deprivation (96 hours) and then evaluate the effects on temperature; and 4) to measure the levels of adenosine and thyroid hormones in blood. One-month-old Wistar male rats (weight 90-100 g) were studied. The thyroid gland was removed, and the parathyroid glands were reimplanted within the neck muscle (Htx) under halothane anesthesia. A sham-operated group was also included (Etx). Four months later, the animals were studied according to the following protocols. Protocol 1: Animals of both groups (i.e. Etx and Htx) were implanted for sleep recordings. After a baseline polysomnography, these animals were REM sleep deprived by the platform method (96 hours). Protocol 2. An intraperitoneal temperature transducer was placed into animals of both groups under deep halothane anesthesia. They were studied at baseline, during 96 hours of REM sleep deprivation, and on the rebound period. Protocol 3: Plasma thyroid hormones [T3, T4, and thyroid-stimulating hormone (TSH)] and plasma adenosine were determined in both groups. Results of protocol 1 indicated that the main difference observed in Htx rats during the baseline sleep was an increase in delta sleep (slow-wave sleep 2) and a reduction in waking time compared with Etx animals. REM sleep rebound after 96 hours of REM sleep deprivation was similar in both groups. In protocol 2, the main finding was that Htx animals had reduced body temperature. A significant difference in body temperature between Etx and Htx animals was found mainly during lights-on period. REM sleep deprivation in the Etx group produced an increase in body temperature. Htx animals showed the opposite effect, with a reduction in body temperature during and after REM sleep deprivation. In protocol 3, the main findings were that Htx animals exhibited a significant reduction in blood thyroid hormones (T3, T4), and that they also had high levels of plasma adenosine. REM sleep deprivation produces changes in temperature regulation. The increase in body temperature during REM sleep deprivation may require thyroid integrity. Absence of the thyroid gland does not seem to influence REM sleep recovery after its deprivation. The high plasma adenosine levels found in the Htx group may explain the increase in delta sleep in this group.     

Localization of pontine PGO wave generation sites and their anatomical projections in the rat

A number of experimental and theoretical reports have suggested that the ponto-geniculo-occipital (PGO) wave-generating cells are involved in the generation of rapid eye movement (REM) sleep and REM sleep dependent cognitive functions. No studies to date have examined anatomical projections from PGO-generating cells to those brain structures involved in REM sleep generation and cognitive functions. In the present study, pontine PGO wave-generating sites were mapped by microinjecting carbachol in 74 sites of the rat brainstem. Those microinjections elicited PGO waves only when made in the dorsal part of the nucleus subcoeruleus of the pons. In six rats, the anterograde tracer biotinylated dextran amine (BDA) was microinjected into the physiologically identified cholinoceptive pontine PGO-generating site to identify brain structures receiving efferent projections from those PGO-generating sites. In all cases, small volume injections of BDA in the cholinoceptive pontine PGO-generating sites resulted in anterograde labeling of fibers and terminals in many regions of the brain. The most important output structures of those PGO-generating cells were the occipital cortex, entorhinal cortex, piriform cortex, amygdala, hippocampus, and many other thalamic, hypothalamic, and brainstem nuclei that participate in the generation of REM sleep. These findings provide anatomical evidence for the hypothesis that the PGO-generating cells in the pons could be involved in the generation of REM sleep. Since PGO-generating cells project to the entorhinal cortex, piriform cortex, amygdala, and hippocampus, these PGO-generating cells could also be involved in the modulation of cognitive functions.     

The development of falling asleep during the first months of life in man (author's transl)

Ten normal infants were studied at 2, 6, 12 and 20 weeks of age. EEG, respiratory rhythm, eye movements and chin EMG were recorded after the evening meal. Recording was continued during the stages of sleep. During the period of falling asleep the periods of REM sleep have been analyzed and compared with the periods of REM sleep occurring after non-REM sleep. REM sleep occurring on falling asleep and that occurring after non-REM sleep differed. Some of the following criteria were different at the earliest time of examination; absence of chin EMG activity, number of apnoeic episodes; other criteria (eye movements, respiration) differed during the first 5 months. The large number of eye movements at 2 and 6 weeks and the high respiratory rate, corresponding to that occurring during waking, could indicate that during REM sleep occurring on falling asleep, one is observing manifestations connected with the waking state.     

Acute von Willebrand factor secretion from the endothelium in vivo: assessment through plasma propeptide (vWf:AgII) Levels

STUDY OBJECTIVES: Patients with coronary heart disease (CHD) and obstructive sleep apnea may have an increased cardiac risk due to nocturnal myocardial ischemia triggered by apnea-associated oxygen desaturation. Sleep structure in patients with obstructive sleep apnea is fragmented by activation of the central nervous system (CNS) (arousal) due to obstructive apneas. Nocturnal myocardial ischemia may lead to activation of the CNS as well. PATIENTS: Fourteen patients with obstructive sleep apnea and CHD disease and seven patients suffering from obstructive sleep apnea without CHD were studied. Overnight sleep studies and simultaneous six-lead ECG recordings were performed. In addition, sleep studies and ECG recordings were performed with administration of a sustained-release nitrate in these patients in a double-blinded crossover design. RESULTS: Analysis of three nights' recordings revealed 144 episodes of nocturnal myocardial ischemia in six subjects. Five patients had underlying CHD and one patient exhibited diffuse wall defects of the coronary arteries; also, 85.4% of ischemic episodes were concomitant with apneas and oxygen desaturation > 3%, and 77.8% of ischemic episodes occurred during rapid eye movement (REM) sleep, although total amount of REM sleep was only 18% of total sleep time. Mean oxygen saturation was significantly lower (p < 0.05) during apnea-associated ischemic episodes than during nonapnea-associated ischemia (77.3% vs 93.1%). Nitrate administration did not reduce ischemic episodes. Sleep architecture (macrostructure) exhibited a reduction in sleep stages non-REM 3 and 4 and REM sleep. Comparing the microstructure of sleep (arousals) within episodes with and without ischemia but similar criteria like sleep stage, apnea activity, and oxygen saturation, we found significantly more (p < 0.01) and severe (p < 0.001) arousals during periods with myocardial ischemia than during control episodes. In addition, microstructure of sleep was disturbed by myocardial ischemia itself in absence of apneas. CONCLUSION: It is concluded that patients with CHD and obstructive sleep apnea are endangered by apnea-associated ischemia and that these ischemic episodes lead to activation of the CNS and additional fragmentation of sleep. Patients with nocturnal ischemia should be screened for underlying sleep apnea even if nitrate therapy fails.     

Prevalence of Listeria sp. in droppings from urban rooks (Corvus frugilegus)

Rapid eye movement (REM) sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase) controls acetylcholine (Ach) availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12). Two additional groups, a home-cage control (N = 6) and a large platform control (N = 6), were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant), membrane-bound (100,000 g pellet) and soluble (100,000 g supernatant) Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet) enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) in the 100,000 g pellet enzyme preparation (home-cage group 152.1 +/- 5.7, large platform group 152.7 +/- 24.9 and REM sleep-deprived group 127.9 +/- 13.8). There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 +/- 21.5, large platform group 127.8 +/- 20.4, REM sleep-deprived group 102.8 +/- 14.2). Our results suggest that REM sleep deprivation changes Ach availability at the level of its receptors through a decrease in Achase activity.     

A dynamic and quantitative study of pattern visual evoked potentials and gamma-aminobutyric acid neurones in the lateral geniculate nucleus and the visual cortex of monocular deprivation cats

PURPOSE: To assess the effects of monocular lid closure during critical period on cortical activity. METHOD: Pattern visual evoked potentials (PVEP) of the normal and the monocular deprivation (MD) cats were dynamically measured and the number of gammaaminobutyric acid immunopositive (GABA-IP) neurones of the area 17 of the visual cortex and the lateral geniculate nucleus (LGN) was quantitatively compared by using immunohistochemical method (ABC). RESULTS: The amplitude of the N1-P1 attenuated in deprived eyes (DE), NE/DE at postnatal week (PNW) 7-8 (P < 0.05), NE/DE at PNW 15-16 (P < 0.01); while P1 latency delayed, NE/DE at PNW 7-8 (P > 0.05), NE/DE at PNW 15-16 (P< 0.05). The numbers of GABA-IP neurones in layer A1 of the ipsilateral LGN and in layer A of the contralateral LGN, compared to those in the corresponding normal laminae, were not significant at PNW 7-8 and PNW 11-12 (P > 0.05), while in the same cats a reduction in the number of GABA-IP neurones was found in layer IV of area 17 at PNW 11-12 (P < 0.05). However, with longer survival of 3-4 weeks in duration, the numbers of GABA-IP neurones in the deprived laminae of LGN were remarkably reduced (P < 0.05). CONCLUSIONS: The amplitude of N1-P1 components is sensitive to the effects of monocular deprivation. Monocular deprivation in cats during critical period leads to dramatic changes of the number of GABA-IP neurones in the LGN and cortical layer IV receiving inputs from the deprived eye in cats. The deprivation-induced reduction in GABA-IP neurones is delayed in the LGN compared with the visual cortex. PVEP of the MD cats is consistent with the damage of its GABA system in visual cortex.     

Arousal responses to inspiratory resistive loading during REM and non-REM sleep in normal men after short-term fragmentation/deprivation

The arousal response to inspiratory resistive loading in normal men is known to be high during REM sleep compared to non-REM sleep. We investigated whether we could observe the same pattern, i.e. brisk arousal from REM sleep compared to non-REM sleep, in normal subjects who had undergone short-term sleep fragmentation/deprivation prior to the investigation. The arousal response to the repeated application of an external inspiratory resistance of 25 cm H2O/l/s was determined during REM and non-REM sleep in 10 healthy men after a single night with 4 hours of acoustically fragmented sleep. The percentage of arousals to non-arousals occurring within 2 minutes of the load application was significantly higher during REM sleep than during either of the non-REM sleep stages 2 and 3/4 and decreased significantly from stage REM to stage 2 and from stage 2 to stage 3/4. The mean time to arousal in REM was significantly shorter than in non-REM stage 3/4. The duration of sleep (comparing the results of the first with the second half of the sleep period time) did not modify the arousal response in stages 2 and 3/4. Despite short-term sleep fragmentation/deprivation the night before the study, the arousal response to external inspiratory resistive loading was brisker during REM than non-REM sleep in the healthy subjects studied. The responses were of the same magnitude as those induced in prior studies without pretest sleep disturbance. This is different from what is seen in patients with sleep apnea, where breathing disorders are worst during REM sleep and sleep fragmentation/deprivation leads to rapid deterioration of arousal responses to the spontaneously occurring airway occlusions.     

Bilateral periventricular nodular heterotopia with mental retardation and frontonasal malformation

So far, sleep researches have been improved by tight collaborations between behavioral and modeling studies. From the novel point of view, we developed the thermoregulatory model of sleep control, which reproduces the well-known features of human sleep-waking cycles. The biphasic daily pattern of sleepiness and the resulting behavior during sleep deprivation are mechanistically interpreted by reducing them into the behavior of the model elements. In addition, a physiological mechanism underlying REM (rapid eye movement sleep) regulation is modelled based on the recent physiological knowledge, which could be a novel explanation instead of the reciprocally interacting model of REM generation (McCarley et al, 1975). Our model successfully produces the limit cycle of REM-related neuronal activities.     

Sleep architecture in a canine model of obstructive sleep apnea

Obstructive sleep apnea (OSA) causes recurrent sleep disruption that is thought to contribute to excessive daytime sleepiness in patients with this disorder. The purpose of this study was to determine the specific effects of OSA on overall sleep architecture in a canine model of OSA. The advantage of this model is that sleep during long-term OSA can be compared to both normal sleep before OSA and recovery sleep after OSA. Studies were performed in four dogs in which sleep-wake state was monitored continuously by a computer that received telemetered EEG and EMG signals. Whenever sleep was detected, the computer sent a signal to close a valve through which the dog breathed; when the dog awoke the occlusion was released. In each dog, data were analyzed from 4 consecutive nights in three phases: a control phase before induction of OSA, a phase during long-term OSA (mean = 85 days, apnea index = 59/hour), and a recovery phase after cessation of OSA. During recovery there was a significant increase in the amount of rapid-eye-movement (REM) sleep compared to the OSA phase (p < 0.01), as well as significant increases in sleep efficiency and decreases in wakefulness (p < 0.01), similar to that reported in OSA patients. The REM rebound during recovery, however, could not be attributed to overall REM deprivation since the amount of REM sleep during the OSA phase was not different from the control phase (p = 0.708). This finding suggests that REM rebound during recovery from OSA is not the result of an overall REM sleep deficit per se. Rather, repeated sleep disruption due to the effects of repetitive apneas and hypoxia may lead to an increased REM sleep drive that manifests itself as a REM sleep rebound during recovery sleep after OSA.     

Rapid eye movement sleep correlates with the overall activities of the hypothalamic-pituitary-adrenal axis and sympathetic system in healthy humans

To assess the association of the overall amount of rapid eye movement (REM) sleep and the activities of the hypothalamic-pituitary-adrenal axis and sympathetic system, we performed polysomnography and measured 24-h urinary free cortisol and catecholamine excretion in 21 healthy adults. After an adaptation night, each subject was recorded in the sleep laboratory for 3 consecutive nights while 24-h urine specimens were collected. Urinary free cortisol, epinephrine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid levels were significantly and positively correlated with the average values of percent REM sleep (P < 0.05). There were no correlations between hormone values and REM latency, other variables of REM distribution, or REM density, an index of phasic activity during REM sleep. The positive correlations between stress system activity and REM sleep are consistent with hormonal and sleep alterations in melancholic depression, a state characterized by increased cortisol and catecholamine secretion.     

The influence of a heavy thermal load on REM sleep in the rat

This study was carried out in order to further test the hypothesis that the occurrence of REM sleep in the rat in the form of episodes separated by long intervals (single REM sleep episodes) and by short intervals (sequential REM sleep episodes) is differently influenced by changes in both sleep and ambient related processes. Rats were studied during the exposure to Ta -10 degrees C for 24 or 48 h and during a 12 h recovery period at laboratory Ta (23 degrees C) following either the first or the second 24 h of cold exposure. The exposure to such a low Ta induced an almost complete abolition of REM sleep which was followed, during recovery, by a marked REM sleep rebound. However, in spite of the larger REM sleep deprivation, the REM sleep rebound was weaker following the 48 h-exposure than that following the exposure for 24 h. The increase in the amount of REM sleep during the recovery period was due to an increase in the amount of that occurring in the form of sequential episodes, whilst that in the form of single episodes did not change with respect to control levels. However, the occurrence of REM sleep in the form of sequential episodes was partially impaired during the REM sleep rebound observed in the recovery period following the 48 h-exposure. These results would suggest that the homeostatic regulation of physiological variables may conflict with that of REM sleep occurrence and that the degree of such a contrast is indicated, at low Ta, by the amount of REM sleep in the form of single episodes and, during the following recovery, by the amount of REM sleep in the form of sequential episodes.     

Respiratory and body movements as indicators of sleep stage and wakefulness in infants and young children

Conventional polysomnographic (PSG) sleep staging to sleep staging based on a static-charge-sensitive bed (SCSB) recording in infants and young children was compared. The study consisted of whole-night clinical sleep studies in 22 children at 24 weeks (SD 24, range 1-79 weeks) of age. Most of the children presented with respiratory disturbances during sleep. From the SCSB record, sleep stages were differentiated according to regularity of breathing, presence of body movements, and most important, presence of high-frequency components of breathing (SCSB spikes). With both methods, three sleep/wake stages were distinguished: rapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep and wakefulness. The average interscorer reliability of the PSG sleep staging controlled in nine subjects was 88%. The average concordance between the two methods ranged from 82 to 85%, depending on the criteria used for scoring the SCSB. The mean sensitivity of the SCSB to detect NREM sleep ranged from 77 to 90% and the mean sensitivity to detect REM sleep ranged from 61 to 86%. The mean positive predictive value was 89-96% for NREM sleep and 54-67% for REM sleep. In conclusion, REM sleep is characterized by irregular breathing with superimposed fast respiratory movements. These changes are specific enough to allow distinction between episodes of NREM sleep, REM sleep and wakefulness with the non-invasive SCSB method in infants and young children. Incomplete concordance between PSG and SCSB score was most frequently observed during sleep stage transition periods, where the behavioural state and electrophysiological criteria disagreed. When combined with the PSG, the SCSB provides complementary information about the behavioural state of child.     

Interhemispheric asymmetry of human sleep EEG in response to selective slow-wave sleep deprivation.

Recent evidence suggests that the human sleep electroencephalogram (EEG) shows regional differences over both the sagittal and coronal planes. In the present study, in a group of 10 right-handers, the authors investigated the presence of hemispheric asymmetries in the homeostatic regulation of human sleep EEG power during and after selective slow-wave sleep (SWS) deprivation. The SWS deprivation was slightly more effective over the right hemisphere, but the left hemisphere showed a markedly larger increase of EEG power in the 1.00-24.75 Hz range during recovery-night non-REM sleep, and a larger increase of EEG power during both deprivation-night and recovery-night REM sleep. These results support the greater need for sleep recuperative processes of the left hemisphere, suggesting that local sleep regulation processes may also act during REM sleep. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contributions of the pedunculopontine region to normal and altered REM sleep

The pedunculopontine (PPN) region of the upper brainstem is recognized as a critical modulator of activated behavioral states such as wakefulness and rapid eye movement (REM) sleep. The expression of REM sleep-related physiology (e.g. thalamocortical arousal, ponto-geniculate-occipital (PGO) waves, and atonia) depends upon a subpopulation of PPN neurons that release acetylcholine (ACh) to act upon muscarinic receptors (mAChRs). Serotonin's potent hyperpolarization of cholinergic PPN neurons is central to present working models of REM sleep control. A growing body of experimental evidence and clinical experience suggests that the responsiveness of the PPN region, and thereby modulation of REM sleep, involves closely adjacent glutamatergic neurons and alternate afferent neurotransmitters. Although many of these afferents are yet to be defined, dopamine-sensitive GABAergic pathways exiting the main output nuclei of the basal ganglia and adjacent forebrain nuclei appear to be the most conspicuous and the most likely to be clinically relevant. These GABAergic pathways are ideally sited to modulate the physiologic hallmarks of REM sleep differentially (e.g. atonia versus cortical activation), because each originates from a functionally unique forebrain circuit and terminates in a unique pattern upon brain stem neurons with unique membrane characteristics. Evidence is reviewed that changes in the quality, timing, and quantity of REM sleep that characterize narcolepsy, REM sleep behavior disorder, and neurodegenerative and affective disorders (depression and schizophrenia) reflect 1) changes in responsiveness of cells in the PPN region governed by these afferents; 2) increase or decrease in PPN cell number; or 3) mAChRs mediating increased responsiveness to ACh derived from the PPN. Auditory evoked potentials and acoustic startle responses provide means independent from recording sleep to assess pathophysiologies affecting the PPN and its connections and thereby complement investigations of their role in affecting daytime functions (e.g. arousal and attention).     

PAG-microinjected dipyrone (metamizol) inhibits responses of spinal dorsal horn neurons to natural noxious stimulation in rats

Recently, we have shown that rapid eye movement sleep deprivation (REM-SD) in animals with lesions of the nigro-striatal pathway facilitates turning behavior and such increase still occurred even in the presence of dopaminergic grafts. The objective of this work was to determine which DA receptors are preferentially involved. The results showed that the D2 receptor antagonist sulpiride decreases significantly turning behavior of lesioned animals, with no effect whatsoever of the D1 antagonist SCH 23390. When lesioned animals were REM sleep deprived, the D1 but not the D2 receptor antagonist prevented the increase of turning induced by REM-SD. This work suggests that the increase of post-synaptic supersensitivity induced by REM-SD in nigro-striatal lesioned animals is mediated by D1 receptors.     

REM motivation induced by brief REM deprivation: The influence of cognition, gender, and personality.

Prominence of the brain's right-hemisphere information processing and intensity of dream experience have been proposed as important psychological aspects of REM sleep. Either view is consistent with the prediction that the effect of REM deprivation will depend in part on the nature of cognitive activity that is initiated at the onset of each REM period and that "substitutes" for the interrupted REM process. In the present study with 84 female and 73 male undergraduates, the effect of REM deprivation was more striking for females given a digits task than for females given a fantasy-reporting task during awakenings used to induce REM deprivation for the 1st 6 hrs of the night. High neuroticism (Maudsley Personality Inventory) appeared to exaggerate the effect. No corresponding pattern was observed for males. These preliminary findings are in part consistent with the view that the "motive" for REM sleep and dreaming may be exaggerated by cognitive activity that is functionally incongruent with those processes. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)