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Sample records for idiopathic rem sleep

  1. Sleepiness in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease

    PubMed Central

    Arnulf, Isabelle; Neutel, Dulce; Herlin, Bastien; Golmard, Jean-Louis; Leu-Semenescu, Smaranda; Cochen de Cock, Valérie; Vidailhet, Marie

    2015-01-01

    Objective: To determine whether patients with idiopathic and symptomatic RBD were sleepier than controls, and if sleepiness in idiopathic RBD predicted earlier conversion to Parkinson disease. Methods: The Epworth Sleepiness Scale (ESS) and its determinants were compared at the time of a video-polysomnography for an RBD diagnosis in patients with idiopathic RBD, in patients with Parkinson disease, and in controls. Whether sleepiness at time of RBD diagnosis predicted an earlier conversion to neurodegenerative diseases was retrospectively analyzed in the followed-up patients. Results: The 75 patients with idiopathic RBD were sleepier (ESS: 7.8 ± 4.6) at the time of RBD diagnosis than 74 age- and sex-matched controls (ESS: 5.0 ± 3.6, P < 0.0001). They reached the levels of 114 patients with Parkinson disease (ESS: 8.7 ± 4.8), whether they had (n = 78) or did not have (n = 36) concomitant RBD. The severity of sleepiness in idiopathic RBD correlated with younger age, but not with sleep measures. Among the 69 patients with idiopathic RBD who were followed up for a median 3 years (1–15 years), 16 (23.2%) developed parkinsonism (n = 6), dementia (n = 6), dementia plus parkinsonism (n = 2), and multiple system atrophy (n = 2). An ESS greater than 8 at time of RBD diagnosis predicted a shorter time to phenoconversion to parkinsonism and dementia, from RBD onset, and from RBD diagnosis (when adjusted for age and time between RBD onset and diagnosis). Conclusions: Sleepiness is associated with idiopathic REM sleep behavior disorder and predicts more rapid conversion to parkinsonism and dementia, suggesting it is an early marker of neuronal loss in brainstem arousal systems. Citation: Arnulf I, Neutel D, Herlin B, Golmard JL, Leu-Semenescu S, Cochen de Cock V, Vidailhet M. Sleepiness in idiopathic REM sleep behavior disorder and Parkinson disease. SLEEP 2015;38(10):1529–1535. PMID:26085299

  2. Cardiac Autonomic Regulation During Sleep in Idiopathic REM Sleep Behavior Disorder

    PubMed Central

    Lanfranchi, Paola A.; Fradette, Lorraine; Gagnon, Jean-François; Colombo, Roberto; Montplaisir, Jacques

    2007-01-01

    Objective: To assess cardiac autonomic and respiratory changes from stage 2 non-rapid eye movement sleep (NREM) to rapid eye movement (REM) sleep in subjects with idiopathic REM sleep behavior disorder (RBD) and controls. We tested the hypothesis that REM-related cardiorespiratory activation is altered in subjects with RBD. Design: Retrospective case-control study. Setting: University hospital-based sleep research laboratory. Patients: Ten subjects with idiopathic RBD (2 women, mean age 63.4 ± 6.2 years) and 10 sex- and age-matched controls (mean age 63.9 ± 6.3 years). Intervention: One-night polysomnography was used to assess R-R variability during NREM and REM sleep. Measurements and Results: Spectral analysis of R-R interval and respiration were performed. Mean R-R interval, low-frequency (LF) and high-frequency (HF) components in both absolute and normalized units (LFnu and HFnu), and the LF/HF ratio were obtained from 5-minute electrocardiogram segments selected during NREM and REM sleep under stable conditions (stable breathing pattern, no microarousals or leg movements). Respiratory frequency was also assessed. Values obtained were then averaged for each stage and analyzed by 2 × 2 analysis of variance with group (RBD subjects and controls) as factor and state (NREM and REM) as repeated measures. RR interval, HF, and HFnu components decreased from NREM to REM in controls but did not change in RBD subjects (Interaction P < 0.05). LFnu (interaction P < 0. 001), LF/HF (interaction P < 0. 001), and respiratory frequency (interaction P < 0. 05) increased from NREM to REM sleep in controls but remained stable in RBD subjects. Conclusion: REM-related cardiac and respiratory responses are absent in subjects with idiopathic RBD. Citation: Lanfranchi PA; Fradette L; Gagnon JF; Colombo R; Montplaisir J. Cardiac autonomic regulation during sleep in idiopathic REM sleep behavior disorder. SLEEP 2007;30(8):1019–1025. PMID:17702272

  3. Idiopathic REM Sleep Behavior Disorder: A Report on Two Cases with Contrasting Features.

    PubMed

    Gupta, Sriniwas; Raju, M S V K; Pawar, Alka

    2015-01-01

    REM sleep behavior disorder (RBD) is a rare parasomnia in which persons exhibit uncharacteristic violent behavior, while dreaming. Secondary RBD occurs due to some neurological conditions, psychoactive substance or psychotropic drug use. There are no case reports on idiopathic RBD in India. We report here two cases to underscore the importance of identifying the disease as behavior associated with RBD may be quite serious in nature and might lead to catastrophic consequences. PMID:26664088

  4. Idiopathic REM Sleep Behavior Disorder: A Report on Two Cases with Contrasting Features

    PubMed Central

    Gupta, Sriniwas; Raju, M. S. V. K.; Pawar, Alka

    2015-01-01

    REM sleep behavior disorder (RBD) is a rare parasomnia in which persons exhibit uncharacteristic violent behavior, while dreaming. Secondary RBD occurs due to some neurological conditions, psychoactive substance or psychotropic drug use. There are no case reports on idiopathic RBD in India. We report here two cases to underscore the importance of identifying the disease as behavior associated with RBD may be quite serious in nature and might lead to catastrophic consequences. PMID:26664088

  5. Alexithymia Associated with Nightmare Distress in Idiopathic REM Sleep Behavior Disorder

    PubMed Central

    Godin, Isabelle; Montplaisir, Jaques; Gagnon, Jean-François; Nielsen, Tore

    2013-01-01

    Study Objectives: Idiopathic REM sleep behavior disorder (iRBD) is characterized by atypical REM sleep motor activity, vivid dreams and nightmares, and dream-enacting behaviors that can result in injuries to the patient and bed partner. It is also a known predictor of Parkinson disease (PD). Alexithymia has been associated with disturbances in sleep and dreaming (e.g., nightmares) and is a non-motor symptom of PD. We assessed alexithymia and disturbed dreaming in iRBD patients with the aim of determining if these two factors are elevated and interrelated among this population. Design: Questionnaire study of clinically diagnosed patients. Setting: Clinical sleep disorders center. Patients or participants: Thirty-two iRBD patients and 30 healthy age- and sex-matched control participants. Measurements and Results: Participants completed the 20-item Toronto Alexithymia Scale (TAS-20), the Dream Questionnaire, and the Beck Depression Inventory. iRBD patients obtained higher TAS-20 total scores (62.16 ± 13.90) than did controls (52.84 ± 7.62; F1,59 = 10.44, P < 0.01), even when controlling for depressive symptoms, and more frequently attained the suggested cutoff for alexithymia than did controls (P < 0.01). iRBD patients obtained higher scores on the Difficulty Identifying Feelings alexithymia subscale. For both iRBD and control groups, the Difficulty Indentifying Feelings subscale correlated positively with the Nightmare Distress scale of the Dream Questionnaire. Conclusions: Elevated alexithymia scores among idiopathic rapid eye movement sleep behavior disorder patients, and especially a difficulty in identifying feelings, parallels evidence of dysautonomia in this population. The higher incidence of distressing nightmares and the association of nightmares with alexithymia further extend similar findings for both clinical and non-clinical samples and suggest that an affect regulation disturbance may be common to the two sets of symptoms. Citation: Godin I

  6. [REM sleep behavior disorder (RBD) and dissociated REM sleep].

    PubMed

    Watanabe, T; Sugita, Y

    1998-02-01

    REM sleep behavior disorder (RBD) is characterized by the appearance of somnambulism-like behavior associated with dream mentation, and the intermittent loss of muscle atonia during REM sleep (stage 1-REM with tonic EMG; stage 1-REM). RBD is caused symptomatically or idiopathically, and its manifestation of symptoms sometimes associated with psychosocial stress. Muscle tone is often augmented during impared REM sleep observed in RBD patients. Animal experimental studies suggest that dysfunction or lesions of muscle inhibitory system in brain stem is rerated with pathogenesis of RBD. Clonazepam is effective for organic behavior and nightmare, but not remarkable for dissociated REM sleep. Other benzodiazepines and tricyclic antidepressants can be one of the choices of medications. Directions for safe-bedroom and psychotherapy is sometimes necessary. PMID:9503847

  7. REM sleep Behaviour Disorder.

    PubMed

    Ferini-Strambi, Luigi; Rinaldi, Fabrizio; Giora, Enrico; Marelli, Sara; Galbiati, Andrea

    2016-01-01

    Rapid Eye Movement (REM) sleep Behaviour Disorder (RBD) is a REM sleep parasomnia characterized by loss of the muscle atonia that typically occurs during REM sleep, therefore allowing patients to act out their dreams. RBD manifests itself clinically as a violent behaviour occurring during the night, and is detected at the polysomnography by phasic and/or tonic muscle activity on the electromyography channel. In absence of neurological signs or central nervous system lesions, RBD is defined as idiopathic. Nevertheless, in a large number of cases the development of neurodegenerative diseases in RBD patients has been described, with the duration of the follow-up representing a fundamental aspect. A growing number of clinical, neurophysiologic and neuropsychological studies aimed to detect early markers of neurodegenerative dysfunction in RBD patients. Anyway, the evidence of impaired cortical activity, subtle neurocognitive dysfunction, olfactory and autonomic impairment and neuroimaging brain changes in RBD patients is challenging the concept of an idiopathic form of RBD, supporting the idea of RBD as an early manifestation of a more complex neurodegenerative process. PMID:26427638

  8. REM sleep Behaviour Disorder.

    PubMed

    Ferini-Strambi, Luigi; Rinaldi, Fabrizio; Giora, Enrico; Marelli, Sara; Galbiati, Andrea

    2016-01-01

    Rapid Eye Movement (REM) sleep Behaviour Disorder (RBD) is a REM sleep parasomnia characterized by loss of the muscle atonia that typically occurs during REM sleep, therefore allowing patients to act out their dreams. RBD manifests itself clinically as a violent behaviour occurring during the night, and is detected at the polysomnography by phasic and/or tonic muscle activity on the electromyography channel. In absence of neurological signs or central nervous system lesions, RBD is defined as idiopathic. Nevertheless, in a large number of cases the development of neurodegenerative diseases in RBD patients has been described, with the duration of the follow-up representing a fundamental aspect. A growing number of clinical, neurophysiologic and neuropsychological studies aimed to detect early markers of neurodegenerative dysfunction in RBD patients. Anyway, the evidence of impaired cortical activity, subtle neurocognitive dysfunction, olfactory and autonomic impairment and neuroimaging brain changes in RBD patients is challenging the concept of an idiopathic form of RBD, supporting the idea of RBD as an early manifestation of a more complex neurodegenerative process.

  9. Enteric nervous system α-synuclein immunoreactivity in idiopathic REM sleep behavior disorder

    PubMed Central

    Sprenger, Fabienne S.; Stefanova, Nadia; Gelpi, Ellen; Seppi, Klaus; Navarro-Otano, Judith; Offner, Felix; Vilas, Dolores; Valldeoriola, Francesc; Pont-Sunyer, Claustre; Aldecoa, Iban; Gaig, Carles; Gines, Angels; Cuatrecasas, Miriam; Högl, Birgit; Frauscher, Birgit; Iranzo, Alex; Wenning, Gregor K.; Vogel, Wolfgang; Tolosa, Eduardo

    2015-01-01

    Objective: To investigate the expression of α-synuclein in colonic biopsies of patients with idiopathic REM sleep behavior disorder (iRBD) and address if α-synuclein immunostaining of tissue obtained via colonic biopsies holds promise as a diagnostic biomarker for prodromal Parkinson disease (PD). Methods: Patients with iRBD, patients with PD, and healthy controls were prospectively recruited to undergo colonic biopsies for comparison of α-synuclein immunoreactivity patterns between the groups by using 2 different antibodies. Results: There was no difference in colonic mucosal and submucosal immunostaining between groups using the 15G7 α-synuclein antibody, which was found in almost all participants enrolled in this study. By contrast, immunostaining for serine 129-phosphorylated α-synuclein (pSyn) in submucosal nerve fibers or ganglia was found in none of 14 controls but was observed in 4 of 17 participants with iRBD and 1 out of 19 patients with PD. Conclusions: The present findings of pSyn immunostaining of colonic biopsies in a substantial proportion of iRBD participants raise the possibility that this tissue marker may be a suitable candidate to study further as a prodromal PD marker in at-risk cohorts. PMID:26475692

  10. Dreaming without REM sleep.

    PubMed

    Oudiette, Delphine; Dealberto, Marie-José; Uguccioni, Ginevra; Golmard, Jean-Louis; Merino-Andreu, Milagros; Tafti, Mehdi; Garma, Lucile; Schwartz, Sophie; Arnulf, Isabelle

    2012-09-01

    To test whether mental activities collected from non-REM sleep are influenced by REM sleep, we suppressed REM sleep using clomipramine 50mg (an antidepressant) or placebo in the evening, in a double blind cross-over design, in 11 healthy young men. Subjects were awakened every hour and asked about their mental activity. The marked (81%, range 39-98%) REM-sleep suppression induced by clomipramine did not substantially affect any aspects of dream recall (report length, complexity, bizarreness, pleasantness and self-perception of dream or thought-like mentation). Since long, complex and bizarre dreams persist even after suppressing REM sleep either partially or totally, it suggests that the generation of mental activity during sleep is independent of sleep stage.

  11. REM sleep - by default?

    PubMed

    Horne, J A

    2000-12-01

    Elements of three old, overlapping theories of REM sleep (REM) function, the Ontogenetic, Homeostatic and Phylogenetic hypotheses, together still provide a plausible framework - that REM (i) is directed towards early cortical development, (ii) "tones up" the sleeping cortex, (iii) can substitute for wakefulness, (iv) has a calming effect. This framework is developed in the light of recent findings. It is argued that the "primitiveness" of REM and its similarity to wakefulness liken it to a default state of "non-wakefulness" or a waking antagonist, anteceding "true" (non-REM) sleep. The "toning up" is reflected by inhibition of motor, sensory and (importantly) emotional systems, together pointing to integrated "flight or fight" activity, that preoccupies/distracts the organism when non-REM is absent and wakefulness unnecessary. Dreaming facilitates this distraction. In rodents, REM can provide stress coping and calming, but REM deprivation procedures incorporating immobility may further enhance stress and confound outcomes. REM "pressure" (e.g. REM rebounds) may be a default from a loss of inhibition of REM by non-REM. REM can be reduced and/or replaced by wakefulness, without adverse effects. REM has little advantage over wakefulness in providing positive cerebral recovery or memory consolidation. PMID:11118606

  12. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease.

    PubMed

    Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C; Mackay, Clare E; Hu, Michele T M

    2016-08-01

    SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson's disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson's disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson's disease and 10 control subjects received (123)I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep

  13. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson's disease.

    PubMed

    Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C; Mackay, Clare E; Hu, Michele T M

    2016-08-01

    SEE POSTUMA DOI101093/AWW131 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson's disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson's disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson's disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson's disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson's disease and 10 control subjects received (123)I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement sleep

  14. Is the nonREM-REM sleep cycle reset by forced awakenings from REM sleep?

    PubMed

    Grözinger, Michael; Beersma, Domien G M; Fell, Jürgen; Röschke, Joachim

    2002-11-01

    In selective REM sleep deprivation (SRSD), the occurrence of stage REM is repeatedly interrupted by short awakenings. Typically, the interventions aggregate in clusters resembling the REM episodes in undisturbed sleep. This salient phenomenon can easily be explained if the nonREM-REM sleep process is continued during the periods of forced wakefulness. However, earlier studies have alternatively suggested that awakenings from sleep might rather discontinue and reset the ultradian process. Theoretically, the two explanations predict a different distribution of REM episode duration. We evaluated 117 SRSD treatment nights recorded from 14 depressive inpatients receiving low dosages of Trimipramine. The alarms were triggered by an automatic mechanism for the detection of REM sleep and had to be canceled by the subjects themselves. The REM episodes were determined as in undisturbed sleep-they had to include the remaining REM activity and were separated by 30 min without REM epochs. The frequency histogram of REM episodes declined exponentially with episode duration for each of the first four sleep cycles. The duration of nonREM intervals revealed bimodal distributions. These results were found consistent with the model assuming a reset of the ultradian cycle upon awakening. Whether REM or nonREM activity is resumed on return to sleep can be modeled by a random decision whereby the probability for REM sleep might depend on the momentary REM pressure.

  15. REM sleep and neural nets.

    PubMed

    Crick, F; Mitchison, G

    1995-01-01

    The broad features of rapid eye movement (REM) sleep are reviewed. Memory storage in the brain is probably quite unlike that in a digital computer, being distributed, superimposed and robust. Such memory systems are easily overloaded. If the stored memories share common features, random stimulation often produces mixed outputs. Simulations show that such overloading can be reduced by a process we call 'reverse learning'. We propose that this process is what is happening in REM sleep and that it explains in an unforced manner the condensation commonly found in dreams. Evidence for and against the proposed theory is discussed and several alternative theories are briefly described. The absence of REM sleep in the Enchidna and in two species of dolphins (that have relatively large brains) suggests that REM may allow the brain to be smaller than if REM were lacking.

  16. Dissociative symptoms and REM sleep.

    PubMed

    van Heugten-van der Kloet, Dalena; Merckelbach, Harald; Lynn, Steven Jay

    2013-12-01

    Llewellyn has written a fascinating article about rapid eye movement (REM) dreams and how they promote the elaborative encoding of recent memories. The main message of her article is that hyperassociative and fluid cognitive processes during REM dreaming facilitate consolidation. We consider one potential implication of this analysis: the possibility that excessive or out-of-phase REM sleep fuels dissociative symptomatology. Further research is warranted to explore the psychopathological ramifications of Llewellyn's theory. PMID:24304772

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

    PubMed

    Hornung, Orla P; Regen, Francesca; Schredl, Michael; Heuser, Isabella; Danker-Hopfe, Heidi

    2006-02-01

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

  18. REM sleep homeostasis in the absence of REM sleep: Effects of antidepressants.

    PubMed

    McCarthy, Andrew; Wafford, Keith; Shanks, Elaine; Ligocki, Marcin; Edgar, Dale M; Dijk, Derk-Jan

    2016-09-01

    Most antidepressants suppress rapid eye movement (REM) sleep, which is thought to be important to brain function, yet the resulting REM sleep restriction is well tolerated. This study investigated the impact of antidepressants with different mechanisms of action, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCA), on the regulation of REM sleep in rats. REM sleep was first demonstrated to be homeostatically regulated using 5, 8 and 10 h of REM-sleep specific restriction through EEG-triggered arousals, with an average of 91 ± 10% of lost REM sleep recovered following a 26-29 -hour recovery period. Acute treatment with the antidepressants paroxetine, citalopram and imipramine inhibited REM sleep by 84 ± 8, 84 ± 8 and 69 ± 9% respectively relative to vehicle control. The pharmacologically-induced REM sleep deficits by paroxetine and citalopram were not fully recovered, whereas, after imipramine the REM sleep deficit was fully compensated. Given the marked difference between REM sleep recovery following the administration of paroxetine, citalopram, imipramine and REM sleep restriction, the homeostatic response was further examined by pairing REM sleep specific restriction with the three antidepressants. Surprisingly, the physiologically-induced REM sleep deficits incurred prior to suppression of REM sleep by all antidepressants was consistently recovered. The data indicate that REM sleep homeostasis remains operative following subsequent treatment with antidepressants and is unaffected by additional pharmacological inhibition of REM sleep. PMID:27150557

  19. REM sleep homeostasis in the absence of REM sleep: Effects of antidepressants.

    PubMed

    McCarthy, Andrew; Wafford, Keith; Shanks, Elaine; Ligocki, Marcin; Edgar, Dale M; Dijk, Derk-Jan

    2016-09-01

    Most antidepressants suppress rapid eye movement (REM) sleep, which is thought to be important to brain function, yet the resulting REM sleep restriction is well tolerated. This study investigated the impact of antidepressants with different mechanisms of action, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCA), on the regulation of REM sleep in rats. REM sleep was first demonstrated to be homeostatically regulated using 5, 8 and 10 h of REM-sleep specific restriction through EEG-triggered arousals, with an average of 91 ± 10% of lost REM sleep recovered following a 26-29 -hour recovery period. Acute treatment with the antidepressants paroxetine, citalopram and imipramine inhibited REM sleep by 84 ± 8, 84 ± 8 and 69 ± 9% respectively relative to vehicle control. The pharmacologically-induced REM sleep deficits by paroxetine and citalopram were not fully recovered, whereas, after imipramine the REM sleep deficit was fully compensated. Given the marked difference between REM sleep recovery following the administration of paroxetine, citalopram, imipramine and REM sleep restriction, the homeostatic response was further examined by pairing REM sleep specific restriction with the three antidepressants. Surprisingly, the physiologically-induced REM sleep deficits incurred prior to suppression of REM sleep by all antidepressants was consistently recovered. The data indicate that REM sleep homeostasis remains operative following subsequent treatment with antidepressants and is unaffected by additional pharmacological inhibition of REM sleep.

  20. Selective REM sleep deprivation in narcolepsy.

    PubMed

    Vu, Manh Hoang; Hurni, Christoph; Mathis, Johannes; Roth, Corinne; Bassetti, Claudio L

    2011-03-01

    Narcolepsy is characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, including cataplexy. The aim of this study was to assess REM sleep pressure and homeostasis in narcolepsy. Six patients with narcolepsy and six healthy controls underwent a REM sleep deprivation protocol, including one habituation, one baseline, two deprivation nights (D1, D2) and one recovery night. Multiple sleep latency tests (MSLTs) were performed during the day after baseline and after D2. During D1 and D2 REM sleep was prevented by awakening the subjects at the first polysomnographic signs of REM sleep for 2 min. Mean sleep latency and number of sleep-onset REM periods (SOREMs) were determined on all MSLT. More interventions were required to prevent REM sleep in narcoleptics compared with control subjects during D1 (57 ± 16 versus 24 ± 10) and D2 (87 ± 22 versus 35 ± 8, P = 0.004). Interventions increased from D1 to D2 by 46% in controls and by 53% in narcoleptics (P < 0.03). Selective REM sleep deprivation was successful in both controls (mean reduction of REM to 6% of baseline) and narcoleptics (11%). Both groups had a reduction of total sleep time during the deprivation nights (P = 0.03). Neither group had REM sleep rebound in the recovery night. Narcoleptics had, however, an increase in the number of SOREMs on MSLT (P = 0.005). There was no increase in the number of cataplexies after selective REM sleep deprivation. We conclude that: (i) REM sleep pressure is higher in narcoleptics; (ii) REM sleep homeostasis is similar in narcoleptics and controls; (iii) in narcoleptics selective REM sleep deprivation may have an effect on sleep propensity but not on cataplexy.

  1. Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease

    PubMed Central

    Rolinski, Michal; Griffanti, Ludovica; Piccini, Paola; Roussakis, Andreas A.; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.; Quinnell, Timothy; Zaiwalla, Zenobia; Klein, Johannes C.; Mackay, Clare E.

    2016-01-01

    See Postuma (doi:10.1093/aww131) for a scientific commentary on this article. Resting state functional magnetic resonance imaging dysfunction within the basal ganglia network is a feature of early Parkinson’s disease and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder, a condition associated with a high rate of future conversion to Parkinson’s disease. In this study, we explore the utility of resting state functional magnetic resonance imaging to detect basal ganglia network dysfunction in rapid eye movement sleep behaviour disorder. We compare these data to a set of healthy control subjects, and to a set of patients with established early Parkinson’s disease. Furthermore, we explore the relationship between resting state functional magnetic resonance imaging basal ganglia network dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerized tomography, and perform morphometric analyses to assess grey matter loss. Twenty-six patients with polysomnographically-established rapid eye movement sleep behaviour disorder, 48 patients with Parkinson’s disease and 23 healthy control subjects were included in this study. Resting state networks were isolated from task-free functional magnetic resonance imaging data using dual regression with a template derived from a separate cohort of 80 elderly healthy control participants. Resting state functional magnetic resonance imaging parameter estimates were extracted from the study subjects in the basal ganglia network. In addition, eight patients with rapid eye movement sleep behaviour disorder, 10 with Parkinson’s disease and 10 control subjects received 123I-ioflupane single photon emission computerized tomography. We tested for reduction of basal ganglia network connectivity, and for loss of tracer uptake in rapid eye movement

  2. Biperiden administration during REM sleep deprivation diminished the frequency of REM sleep attempts.

    PubMed

    Salin-Pascual, R J; Grandos-Fuentes, D; Galicia-Polo, L; Nieves, E; Roehrs, T A; Roth, T

    1992-06-01

    Sixteen subjects were assigned to a group using either placebo or biperiden, with eight subjects in each group. Both groups were studied for one acclimatization night, one baseline night, four nights of rapid eye movement (REM) sleep deprivation and two recovery nights. All the subjects received either placebo or 4 mg biperiden 1 hour before sleep during the four nights of REM sleep deprivation. During the baseline and the recovery nights both groups received placebo capsules. The results showed that REM sleep time during the REM sleep deprivation was reduced by 70-75% below the baseline night in both groups. The number of attempts to enter REM sleep was significantly reduced by biperiden as compared to placebo for each of the four REM sleep deprivation nights. Because the total sleep time in the biperiden group was reduced, the number of REM sleep attempts was corrected by the total sleep time. The adjusted number of REM sleep attempts was also significantly reduced in the biperiden group. REM sleep latency showed a reduction in the placebo group, whereas in the biperiden group REM sleep latency was unchanged throughout the deprivation nights. In the recovery night REM sleep time was increased in both groups, with no differences between the groups. The REM sleep latency showed a reduction in the first recovery night in both groups that persisted through the second recovery night. The above findings support the role of biperiden as a REM sleep suppressive drug.

  3. REM sleep predicts subsequent food intake.

    PubMed

    Siegel, J M

    1975-10-01

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

  4. Clinical Considerations of Obstructive Sleep Apnea with Little REM Sleep

    PubMed Central

    Koo, Dae Lim

    2016-01-01

    Background and Purpose Obstructive sleep apnea (OSA) is more severe during rapid eye movement (REM) sleep than during non-REM sleep. We aimed to determine the features of patients with OSA who experience little REM sleep. Methods Patients with a chief complaint of sleep-disordered breathing were enrolled. All subjects underwent overnight polysomnography (PSG) and completed questionnaires on sleep quality. Patients were divided into the following three groups according to the proportion of REM sleep detected in overnight PSG: little REM sleep [REM sleep <20% of total sleep time (TST)], normal REM sleep (20–25% of TST), and excessive REM sleep (>25% of TST). Multiple logistic regression analyses were applied to the data. The success rate of continuous positive airway pressure (CPAP) titration was estimated in these groups. Results The age and body mass index of the patients were 47.9±15.9 years (mean±SD) and 25.2±4.1 kg/m2, respectively. The 902 patients comprised 684 (76%) men and 218 (24%) women. The apnea-hypopnea index (AHI) in the little-REM-sleep group was 22.1±24.4 events/hour, which was significantly higher than those in the other two groups (p<0.05). Multiple logistic regression showed that a higher AHI (p<0.001; odds ratio, 1.512; 95% confidence interval, 1.020–1.812) was independently predictive of little REM sleep. The titration success rate was lower in the little-REM-sleep group than in the normal-REM-sleep group (p=0.038). Conclusions The AHI is higher and the success rate of CPAP titration is lower in OSA patients with little REM sleep than those with normal REM sleep.

  5. Short-term homeostasis of REM sleep assessed in an intermittent REM sleep deprivation protocol in the rat.

    PubMed

    Ocampo-Garcés, Adrián; Vivaldi, Ennio A

    2002-03-01

    An intermittent rapid eye movement (REM) sleep deprivation protocol was applied to determine whether an increase in REM sleep propensity occurs throughout an interval without REM sleep comparable with the spontaneous sleep cycle of the rat. Seven chronically implanted rats under a 12 : 12 light-dark schedule were subjected to an intermittent REM sleep deprivation protocol that started at hour 6 after lights-on and lasted for 3 h. It consisted of six instances of a 10-min REM sleep permission window alternating with a 20-min REM sleep deprivation window. REM sleep increased throughout the protocol, so that total REM sleep in the two REM sleep permission windows of the third hour became comparable with that expected in the corresponding baseline hour. Attempted REM sleep transitions were already increased in the second deprivation window. Attempted transitions to REM sleep were more frequent in the second than in the first half of any 20-min deprivation window. From one deprivation window to the next, transitions to REM sleep changed in correspondence to the amount of REM sleep in the permission window in-between. Our results suggest that: (i) REM sleep pressure increases throughout a time segment similar in duration to a spontaneous interval without REM sleep; (ii) it diminishes during REM sleep occurrence; and (iii) that drop is proportional to the intervening amount of REM sleep. These results are consistent with a homeostatic REM sleep regulatory mechanism that operates in the time scale of spontaneous sleep cycle.

  6. Does obstructive sleep apnea worsen during REM sleep?

    PubMed

    Peregrim, I; Grešová, S; Pallayová, M; Fulton, B L; Štimmelová, J; Bačová, I; Mikuľaková, A; Tomori, Z; Donič, V

    2013-01-01

    Although it is thought that obstructive sleep apnea (OSA) is worse during rapid eye movement (REM) sleep than in non-REM (NREM) sleep there are some uncertainties, especially about apnoe-hypopnoe-index (AHI). Several studies found no significant difference in AHI between both sleep stages. However, REM sleep is associated more with side sleeping compared to NREM sleep, which suggests that body position is a possible confounding factor. The main purpose of this study was to compare the AHI in REM and NREM sleep in both supine and lateral body position. A retrospective study was performed on 422 consecutive patients who underwent an overnight polysomnography. Women had higher AHI in REM sleep than NREM sleep in both supine (46.05+/-26.26 vs. 23.91+/-30.96, P<0.01) and lateral (18.16+/-27.68 vs. 11.30+/-21.09, P<0.01) body position. Men had higher AHI in REM sleep than NREM sleep in lateral body position (28.94+/-28.44 vs. 23.58+/-27.31, P<0.01), however, they did not reach statistical significance in supine position (49.12+/-32.03 in REM sleep vs. 45.78+/-34.02 in NREM sleep, P=0.50). In conclusion, our data suggest that REM sleep is a contributing factor for OSA in women as well as in men, at least in lateral position. PMID:24020811

  7. REM sleep behavior disorder: from dreams to neurodegeneration.

    PubMed

    Postuma, Ronald B; Gagnon, Jean-Francois; Montplaisir, Jacques Y

    2012-06-01

    REM sleep behavior disorder is a unique parasomnia characterized by dream enactment behavior during REM sleep. Unless triggered by pharmacologic agents such as antidepressants, it is generally related to damage of pontomedullary brainstem structures. Idiopathic REM sleep behavior disorder (RBD) is a well-established risk factor for neurodegenerative disease. Prospective studies have estimated that at least 40-65% of patients with idiopathic RBD will eventually develop a defined neurodegenerative phenotype, almost always a 'synucleinopathy' (Parkinson's disease, Lewy Body dementia or multiple system atrophy). In most cases, patients appear to develop a syndrome with overlapping features of both Parkinson's disease and Lewy body dementia. The interval between RBD onset and disease onset averages 10-15 years, suggesting a promisingly large window for intervention into preclinical disease stages. The ability of RBD to predict disease has major implications for design and development of neuroprotective therapy, and testing of other predictive markers of synuclein-mediated neurodegeneration. Recent studies in idiopathic RBD patients have demonstrated that olfaction, color vision, severity of REM atonia loss, transcranial ultrasound of the substantia nigra, and dopaminergic neuroimaging can predict development of neurodegenerative disease.

  8. Physiology of REM sleep, cataplexy, and sleep paralysis.

    PubMed

    Hishikawa, Y; Shimizu, T

    1995-01-01

    The main neural structures generating muscle atonia and other phenomena characteristic of REM sleep are present in dorsolateral portions of the pons in the brainstem. Occurrence of REM sleep and the NREM-REM sleep cycle are probably determined by a balance or interaction between the cholinergic and cholinoceptive REM sleep-on neuronal populations and the monoaminergic REM sleep-off neuronal population. Neural activities producing generalized muscle atonia in REM sleep originate mainly in dorsolateral portions of the pontine reticular formation, descend through the medulla and spinal cord, and inhibit the motoneurons in the brainstem and spinal cord, bringing about postural atonia. Cataplexy and sleep paralysis are pathological, dissociated manifestations of the generalized muscle atonia characteristic REM sleep. Cataplexy is triggered by emotional stimuli, probably through activation of the neural structure generating the muscle atonia of REM sleep. During long-lasting cataplectic attacks, narcoleptic humans often experience sleep paralysis and vivid hypnagogic hallucinations in the latter sleep state. Sleep paralysis is caused by the marked dissociation between level of alertness and muscle atonia that often occurs in SOREM sleep episodes. Frequent SOREM sleep episodes in narcoleptic humans and dogs may occur when some of the neural mechanisms producing wakefulness and/or NREM sleep that normally inhibit the occurrence of REM sleep are abnormally weak, or when neural mechanisms facilitating the occurrence of REM sleep are hypersensitive or hyperactive, or both. Both abnormalities may contribute to the occurrence of SOREM sleep episodes and sleep paralysis, and also to the emotional triggering of cataplexy. Frequent occurrence of SOREM sleep episodes seems to be prerequisite but not sufficient for the occurrence of cataplexy. Some additional neural activities induced by emotion also contribute by inhibiting and/or activating the disturbed neural mechanisms related

  9. REM sleep, energy balance and 'optimal foraging'.

    PubMed

    Horne, Jim

    2009-03-01

    Mechanisms underlying mammalian REM sleep (REM) indicate commonality with feeding and energy balance. REM 'epiphenomena' may facilitate this, in providing heat conservation and appetite modulation, with the atonia reflecting search (foraging?) behaviour, and the lost neck muscle tonus a suppressed ingestion. In rodents, REM deprivation severely undermines energy balance. It is argued that REM may also facilitate 'optimal foraging' in wakefulness by updating 'decisions' about: appropriate food, where to find it, allocation of time in obtaining it, the locomotion/energy expenditure required to do so, vs. risk of predation. Whereas REM in the early sleep period is oriented to this updating, later REM can put feeding 'on hold'. PGO intensity changes over successive REM periods may reflect this shift. Humans, pets, zoo and laboratory mammals, and neonates have easy food accessibility, without need to forage, leading to a potential excess of REM in the later sleep period; loss of which has different outcomes to total REM deprivation. A more ecological approach in understanding REM function is desirable.

  10. An experimental antidepressant increases REM sleep.

    PubMed

    Soldatos, C R; Stefanis, C N; Bergiannaki, J D; Christodoulou, C; Botsis, A; Sakkas, P N

    1988-01-01

    1. An experimental antidepressant was studied through sleep laboratory recordings, psychoendocrinological tests and clinical measurements in terms of its efficacy, side effects and effects on sleep. 2. The design included a four-week drug administration period, preceeded and followed by a one week placebo period. 3. In the presence of antidepressant efficacy, the drug did not disturb sleep induction and maintainance. 4. The only effect on sleep stages was an increase of REM sleep during the short-term drug administration period which is contrary to the REM supressant effect of most antidepressants. 5. This finding suggests that REM supression and antidepressant efficacy are not necessarily related. 6. Further, given that the only known action of the drug is its inhibitory effect on GABAergic transmission, one can speculate that GABA mechanisms may be involved in REM sleep modulation. PMID:3241873

  11. Retention over a Period of REM or non-REM Sleep.

    ERIC Educational Resources Information Center

    Tilley, Andrew J.

    1981-01-01

    Subjects, awaked, presented with a word list, and tested with arousal measures, were reawaked during REM or non-REM sleep and retested. Recall was facilitated by REM sleep. It was hypothesized that the high arousal level associated with REM sleep incidentally maintained the memory trace in a more retrievable form. (Author/SJL)

  12. REM Sleep Behavior Disorder and REM Sleep Without Atonia as an Early Manifestation of Degenerative Neurological Disease

    PubMed Central

    McCarter, Stuart J.; St Louis, Erik K.

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by repeated episodes of dream enactment behavior and REM sleep without atonia (RSWA) during polysomnography recording. RSWA is characterized by increased phasic or tonic muscle activity seen on polysomnographic electromyogram channels. RSWA is a requisite diagnostic feature of RBD, but may also be seen in patients without clinical symptoms or signs of dream enactment as an incidental finding in neurologically normal individuals, especially in patients receiving antidepressant therapy. RBD may be idiopathic or symptomatic. Patients with idiopathic RBD often later develop other neurological features including parkinsonism, orthostatic hypotension, anosmia, or cognitive impairment. RSWA without clinical symptoms as well as clinically overt RBD also often occurs concomitantly with the α-synucleinopathy family of neurodegenerative disorders, which includes idiopathic Parkinson disease, Lewy body dementia, and multiple system atrophy. This review article considers the epidemiology of RBD, clinical and polysomnographic diagnostic standards for both RBD and RSWA, previously reported associations of RSWA and RBD with neurodegenerative disorders and other potential causes, the pathophysiology of which brain structures and networks mediate dysregulation of REM sleep muscle atonia, and considerations for the effective and safe management of RBD. PMID:22328094

  13. REM sleep deprivation and food intake.

    PubMed

    Bhanot, J L; Chhina, G S; Singh, B; Sachdeva, U; Kumar, V M

    1989-01-01

    The effect of REM-sleep deprivation (REM-SD) on diet preference was studied in rats. REM-SD for a period of 72 hrs produced an increase in day, night and 24 hrs (day plus night) intakes of Carbohydrate Rich diet (CRD) and Total diet (TD). Body weight (BWt) was also increased. The maximum increase in the above parameters were recorded on the 2nd day of REM-SD. During recovery period the intakes of TD fully recovered, but the BWt and consumption of CRD remained high. Intakes of Balanced diet (BD) remained significantly on the lower side when compared to the pre REM-SD mean values. During REM-SD, the rats preferred CRD than BD. The body temperature did not show any change. The increase in TD intake and BWt could be the result of an increase in insulin level and the change appears to be mediated by the activation of hypothalamic feeding centre.

  14. REM sleep rescues learning from interference.

    PubMed

    McDevitt, Elizabeth A; Duggan, Katherine A; Mednick, Sara C

    2015-07-01

    Classical human memory studies investigating the acquisition of temporally-linked events have found that the memories for two events will interfere with each other and cause forgetting (i.e., interference; Wixted, 2004). Importantly, sleep helps consolidate memories and protect them from subsequent interference (Ellenbogen, Hulbert, Stickgold, Dinges, & Thompson-Schill, 2006). We asked whether sleep can also repair memories that have already been damaged by interference. Using a perceptual learning paradigm, we induced interference either before or after a consolidation period. We varied brain states during consolidation by comparing active wake, quiet wake, and naps with either non-rapid eye movement sleep (NREM), or both NREM and REM sleep. When interference occurred after consolidation, sleep and wake both produced learning. However, interference prior to consolidation impaired memory, with retroactive interference showing more disruption than proactive interference. Sleep rescued learning damaged by interference. Critically, only naps that contained REM sleep were able to rescue learning that was highly disrupted by retroactive interference. Furthermore, the magnitude of rescued learning was correlated with the amount of REM sleep. We demonstrate the first evidence of a process by which the brain can rescue and consolidate memories damaged by interference, and that this process requires REM sleep. We explain these results within a theoretical model that considers how interference during encoding interacts with consolidation processes to predict which memories are retained or lost. PMID:25498222

  15. REM sleep rescues learning from interference.

    PubMed

    McDevitt, Elizabeth A; Duggan, Katherine A; Mednick, Sara C

    2015-07-01

    Classical human memory studies investigating the acquisition of temporally-linked events have found that the memories for two events will interfere with each other and cause forgetting (i.e., interference; Wixted, 2004). Importantly, sleep helps consolidate memories and protect them from subsequent interference (Ellenbogen, Hulbert, Stickgold, Dinges, & Thompson-Schill, 2006). We asked whether sleep can also repair memories that have already been damaged by interference. Using a perceptual learning paradigm, we induced interference either before or after a consolidation period. We varied brain states during consolidation by comparing active wake, quiet wake, and naps with either non-rapid eye movement sleep (NREM), or both NREM and REM sleep. When interference occurred after consolidation, sleep and wake both produced learning. However, interference prior to consolidation impaired memory, with retroactive interference showing more disruption than proactive interference. Sleep rescued learning damaged by interference. Critically, only naps that contained REM sleep were able to rescue learning that was highly disrupted by retroactive interference. Furthermore, the magnitude of rescued learning was correlated with the amount of REM sleep. We demonstrate the first evidence of a process by which the brain can rescue and consolidate memories damaged by interference, and that this process requires REM sleep. We explain these results within a theoretical model that considers how interference during encoding interacts with consolidation processes to predict which memories are retained or lost.

  16. Cells of a common developmental origin regulate REM/non-REM sleep and wakefulness in mice.

    PubMed

    Hayashi, Yu; Kashiwagi, Mitsuaki; Yasuda, Kosuke; Ando, Reiko; Kanuka, Mika; Sakai, Kazuya; Itohara, Shigeyoshi

    2015-11-20

    Mammalian sleep comprises rapid eye movement (REM) sleep and non-REM (NREM) sleep. To functionally isolate from the complex mixture of neurons populating the brainstem pons those involved in switching between REM and NREM sleep, we chemogenetically manipulated neurons of a specific embryonic cell lineage in mice. We identified excitatory glutamatergic neurons that inhibit REM sleep and promote NREM sleep. These neurons shared a common developmental origin with neurons promoting wakefulness; both derived from a pool of proneural hindbrain cells expressing Atoh1 at embryonic day 10.5. We also identified inhibitory γ-aminobutyric acid-releasing neurons that act downstream to inhibit REM sleep. Artificial reduction or prolongation of REM sleep in turn affected slow-wave activity during subsequent NREM sleep, implicating REM sleep in the regulation of NREM sleep.

  17. Characteristics of REM Sleep Behavior Disorder in Childhood

    PubMed Central

    Lloyd, Robin; Tippmann-Peikert, Maja; Slocumb, Nancy; Kotagal, Suresh

    2012-01-01

    Study Objective: To describe our experience regarding the clinical and polysomnographic features of REM sleep behavior disorder (RBD) in childhood. Methods: This was a retrospective chart review of children and adolescents with RBD and REM sleep without atonia. Demographics, and clinical and polysomnographic information were tabulated. Our findings were compared with those in the existing literature. Results: The 15 subjects identified (13 RBD and 2 having REM sleep without atonia) had a mean age at diagnosis of 9.5 years (range 3-17 years); 11/15 (73%) were male. Nightmares were reported in 13/15 and excessive daytime sleepiness in 6/15. Two children had caused bodily harm to bedmate siblings. Comorbidities, which were multiple in some subjects, included anxiety (8/15), attention deficit disorder (10/15), nonspecific developmental delay (6/15), Smith-Magenis syndrome (1/15), pervasive developmental disorder (1/15), narcolepsy (1/15), idiopathic hypersomnia (1/15), and Moebius Syndrome (1/15). Abnormal MRI scans were seen in 5/8 evaluated subjects. Treatments consisted of clonazepam (10/15), melatonin (2/15), and discontinuation of a tricyclic agent (1/15), with a favorable response in 11 of 13. Two of 15 patients with REM sleep without atonia did not require pharmacotherapy. Conclusions: RBD in children may be associated with neurodevelopmental disabilities, narcolepsy, or medication use. It seems to be modestly responsive to benzodiazepines or melatonin. The etiology is distinct from that of common childhood arousal parasomnias and RBD in adults; congenital and neurodevelopmental disorders, medication effect, and narcolepsy coexisted in some, but none had an extrapyramidal neurodegenerative disorder. Citation: Lloyd R; Tippmann-Peikert M; Slocumb N; Kotagal S. Characteristics of REM sleep behavior disorder in childhood. J Clin Sleep Med 2012;8(2):127-131. PMID:22505856

  18. Mechanisms and models of REM sleep control.

    PubMed

    McCarley, R W

    2004-07-01

    The first sections of this paper survey the history and recent developments relevant to the major neurotransmitters and neuromodulators involved in REM sleep control. The last portion of this paper proposes a structural model of cellular interaction that produces the REM sleep cycle, and constitutes a further revision of the reciprocal interaction model This paper proposes seven criteria to define a causal role in REM sleep control for putative neuro-transmitters/modulators. The principal criteria are measurements during behavioral state changes of the extracellular concentrations of the putative substances, and electrophysiological recording of their neuronal source. A cautionary note is that, while pharmacological manipulations are suggestive, they alone do not provide definitive causal evidence. The extensive body of in vivo and in vitro evidence supporting cholinergic promotion of REM sleep via LDT/PPT neuronal activity is surveyed. An interesting question raised by some studies is whether cholinergic influences in rat are less puissant than in cat. At least some of the apparent lesser REM-inducing effect of carbachol in the rat may be due to incomplete control of circadian influences; almost all experiments have been run only in the daytime, inactive period, when REM sleep is more prominent, rather than in the REM-sparse nighttime inactive period. Monoaminergic inhibition of cholinergic neurons, once thought to be the most shaky proposal of the reciprocal interaction model, now enjoys considerable support from both in vivo and in vitro data. However, the observed time course of monoaminergic neurons, their "turning off" discharge activity as REM sleep is approached and entered would seem to be difficult to produce from feedback inhibition, as originally postulated by the reciprocal interaction model. New data suggest the possibility that GABAergic inhibition of Locus Coeruleus and Dorsal Raphe monoaminergic neurons may account for the "REM-off" neurons turning

  19. REM Sleep Behavioral Events and Dreaming

    PubMed Central

    Muntean, Maria-Lucia; Trenkwalder, Claudia; Walters, Arthur S.; Mollenhauer, Brit; Sixel-Döring, Friederike

    2015-01-01

    Study Objectives: To clarify whether motor behaviors and/ or vocalizations during REM sleep, which do not yet fulfill diagnostic criteria for REM sleep behavior disorder (RBD) and were defined as REM sleep behavioral events (RBEs), correspond to dream enactments. Methods: 13 subjects (10 patients with Parkinson disease [PD] and 3 healthy controls) originally identified with RBE in a prospective study (DeNoPa cohort) were reinvestigated 2 years later with 2 nights of video-supported polysomnography (vPSG). The first night was used for sleep parameter analysis. During the 2nd night, subjects were awakened and questioned for dream recall and dream content when purposeful motor behaviors and/or vocalizations became evident during REM sleep. REM sleep without atonia (RWA) was analyzed on chin EMG and the cutoff set at 18.2% as specific for RBD. Results: At the time of this investigation 9 of 13 subjects with previous RBE were identified with RBD based upon clinical and EMG criteria. All recalled vivid dreams, and 7 subjects were able to describe dream content in detail. Four of 13 subjects with RBE showed RWA values below cutoff values for RBD. Three of these 4 subjects recalled having non-threatening dreams, and 2 (of these 3) were able to describe these dreams in detail. Conclusion: RBE with RWA below the RBD defining criteria correlate to dreaming in this selected cohort. There is evidence that RBEs are a precursor to RBD. Citation: Muntean ML, Trenkwalder C, Walters AS, Mollenhauer B, Sixel-Döring F. REM sleep behavioral events and dreaming. J Clin Sleep Med 2015;11(5):537–541. PMID:25665694

  20. Intrahippocampal administration of anandamide increases REM sleep.

    PubMed

    Rueda-Orozco, Pavel Ernesto; Soria-Gómez, Edgar; Montes-Rodríguez, Corinne Jennifer; Pérez-Morales, Marcel; Prospéro-García, Oscar

    2010-04-01

    A nascent literature has postulated endocannabinoids (eCBs) as strong sleep-inducing lipids, particularly rapid-eye-movement sleep (REMs), nevertheless the exact mechanisms behind this effect remain to be determined. Anandamide and 2-arachidonyl glycerol, two of the most important eCBS, are synthesized in the hippocampus. This structure also expresses a high concentration of cannabinoid receptor 1 (CB1). Recent extensive literature supports eCBs as important regulators of hippocampal activity. It has also been shown that these molecules vary their expression on the hippocampus depending on the light-dark cycle. In this context we decided to analyze the effect of intrahippocampal administration of the eCB anandamide (ANA) on the sleep-waking cycle at two points of the light-dark cycle. Our data indicate that the administration of ANA directly into the hippocampus increases REMs in a dose dependent manner during the dark but not during the light phase of the cycle. The increase of REMs was blocked by the CB1 antagonist AM251. This effect was specific for the hippocampus since ANA administrations in the surrounding cortex did not elicit any change in REMs. These results support the idea of a direct relationship between hippocampal activity and sleep mechanisms by means of eCBs. The data presented here show, for the first time that eCBs administered into the hippocampus trigger REMs and support previous studies where chemical stimulation of limbic areas triggered sleep.

  1. [Nightmares and behavior during REM sleep].

    PubMed

    Barraquer I Bordas, L

    2001-05-01

    This study reports the current neurobiologic data on REM sleep including psychoanalysis, distinguishing between the "instincts of pleasure" and the "instincts of death" (Beyond the principles of pleasure, S. Freud, 1920). The award and punishment systems are also reported and current data related to nightmares and mainly dream behavior during REM sleep without atonia are presented underlining the frequency of parasomnia in ponto-cerebellous atrophy and Parkinson's disease. The author emphasizes the need for establishing discussions among the different neuroscientific fields related to these questions.

  2. Role of corticosterone on sleep homeostasis induced by REM sleep deprivation in rats.

    PubMed

    Machado, Ricardo Borges; Tufik, Sergio; Suchecki, Deborah

    2013-01-01

    Sleep is regulated by humoral and homeostatic processes. If on one hand chronic elevation of stress hormones impair sleep, on the other hand, rapid eye movement (REM) sleep deprivation induces elevation of glucocorticoids and time of REM sleep during the recovery period. In the present study we sought to examine whether manipulations of corticosterone levels during REM sleep deprivation would alter the subsequent sleep rebound. Adult male Wistar rats were fit with electrodes for sleep monitoring and submitted to four days of REM sleep deprivation under repeated corticosterone or metyrapone (an inhibitor of corticosterone synthesis) administration. Sleep parameters were continuously recorded throughout the sleep deprivation period and during 3 days of sleep recovery. Plasma levels of adrenocorticotropic hormone and corticosterone were also evaluated. Metyrapone treatment prevented the elevation of corticosterone plasma levels induced by REM sleep deprivation, whereas corticosterone administration to REM sleep-deprived rats resulted in lower corticosterone levels than in non-sleep deprived rats. Nonetheless, both corticosterone and metyrapone administration led to several alterations on sleep homeostasis, including reductions in the amount of non-REM and REM sleep during the recovery period, although corticosterone increased delta activity (1.0-4.0 Hz) during REM sleep deprivation. Metyrapone treatment of REM sleep-deprived rats reduced the number of REM sleep episodes. In conclusion, reduction of corticosterone levels during REM sleep deprivation resulted in impairment of sleep rebound, suggesting that physiological elevation of corticosterone levels resulting from REM sleep deprivation is necessary for plentiful recovery of sleep after this stressful event.

  3. Why does arterial blood pressure rise actively during REM sleep?

    PubMed

    Sei, H; Morita, Y

    1999-02-01

    A large fluctuation in autonomic function is one of the most important characteristics of REM sleep. Arterial blood pressure (AP) increases during the transition from non-REM to REM sleep, showing phasic surges during REM sleep. REM-associated AP changes involve 1) a long-term recovery process after surgery, 2) circadian rhythm, 3) relationships with ambient temperature. REM-associated AP changes are mediated by sympathetic nerves, buffered by baroreflex, abolished in decerebrated cats, and related to hippocampal theta activity in rats. Furthermore, the midbrain dopaminergic system has been recently found to be involved in increases in REM-associated AP. PMID:10408152

  4. Quantification of tonic and phasic muscle activity in REM sleep behavior disorder.

    PubMed

    Mayer, Geert; Kesper, Karl; Ploch, Thomas; Canisius, Sebastian; Penzel, Thomas; Oertel, Wolfgang; Stiasny-Kolster, Karin

    2008-02-01

    REM sleep behavior disorder (RBD) is characterized by excessive tone of the chin muscle and limb movement during sleep. In the past, quantification of increased muscle tone in REM sleep has been performed visually, using no stringent criteria. The aim of this study was to develop an automatic analysis, allowing the quantification of muscle activity and its amplitude for all sleep stages, with a focus on REM sleep in patients with RBD. Forty-eight patients (27 male, 21 female) with RBD were included in the analysis. Twenty-one had idiopathic RBD; 28 had narcolepsy plus RBD. Twenty-five patients without confirmed sleep disorder served as control subjects. The amplitude of the EMG was generated from the difference of the upper and lower envelope of the mentalis muscle recordings. By smoothing the amplitude curve, a threshold curve was defined. Any muscle activity beyond the threshold curve was defined as motor activity. The means of the motor activity per second were summarized statistically and calculated for each sleep stage. Due to variable distribution of REM sleep, the latter was assigned to respective quartiles of the recorded night. Muscle activity was defined according to a histogram as short-lasting (<0.5 second) and long-lasting (>0.5 second) activity. No difference in the distribution of REM sleep/quartile and mean muscle tone throughout the sleep cycle could be found within the RBD groups and control subjects. Muscle activity was in the range of 200 ms. No clusters or regular distribution of muscle activity were found. Long muscle activity in the group with manifest clinical RBD was significantly higher than in control subjects, whereas it was nonsignificantly higher in subclinical RBD. The correlation between the frequency of long muscle activity in REM sleep and age was highly significant only for patients with idiopathic RBD. Automatic analysis of muscle activity in sleep is a reliable, easy method that may easily be used in the evaluation for REM sleep

  5. Posttraining Increases in REM Sleep Intensity Implicate REM Sleep in Memory Processing and Provide a Biological Marker of Learning Potential

    ERIC Educational Resources Information Center

    Nader, Rebecca S.; Smith, Carlyle T.; Nixon, Margaret R.

    2004-01-01

    Posttraining rapid eye movement (REM) sleep has been reported to be important for efficient memory consolidation. The present results demonstrate increases in the intensity of REM sleep during the night of sleep following cognitive procedural/implicit task acquisition. These REM increases manifest as increases in total number of rapid eye…

  6. Analysis of automated quantification of motor activity in REM sleep behaviour disorder.

    PubMed

    Frandsen, Rune; Nikolic, Miki; Zoetmulder, Marielle; Kempfner, Lykke; Jennum, Poul

    2015-10-01

    Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by dream enactment and REM sleep without atonia. Atonia is evaluated on the basis of visual criteria, but there is a need for more objective, quantitative measurements. We aimed to define and optimize a method for establishing baseline and all other parameters in automatic quantifying submental motor activity during REM sleep. We analysed the electromyographic activity of the submental muscle in polysomnographs of 29 patients with idiopathic RBD (iRBD), 29 controls and 43 Parkinson's (PD) patients. Six adjustable parameters for motor activity were defined. Motor activity was detected and quantified automatically. The optimal parameters for separating RBD patients from controls were investigated by identifying the greatest area under the receiver operating curve from a total of 648 possible combinations. The optimal parameters were validated on PD patients. Automatic baseline estimation improved characterization of atonia during REM sleep, as it eliminates inter/intra-observer variability and can be standardized across diagnostic centres. We found an optimized method for quantifying motor activity during REM sleep. The method was stable and can be used to differentiate RBD from controls and to quantify motor activity during REM sleep in patients with neurodegeneration. No control had more than 30% of REM sleep with increased motor activity; patients with known RBD had as low activity as 4.5%. We developed and applied a sensitive, quantitative, automatic algorithm to evaluate loss of atonia in RBD patients. PMID:25923472

  7. Analysis of automated quantification of motor activity in REM sleep behaviour disorder.

    PubMed

    Frandsen, Rune; Nikolic, Miki; Zoetmulder, Marielle; Kempfner, Lykke; Jennum, Poul

    2015-10-01

    Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by dream enactment and REM sleep without atonia. Atonia is evaluated on the basis of visual criteria, but there is a need for more objective, quantitative measurements. We aimed to define and optimize a method for establishing baseline and all other parameters in automatic quantifying submental motor activity during REM sleep. We analysed the electromyographic activity of the submental muscle in polysomnographs of 29 patients with idiopathic RBD (iRBD), 29 controls and 43 Parkinson's (PD) patients. Six adjustable parameters for motor activity were defined. Motor activity was detected and quantified automatically. The optimal parameters for separating RBD patients from controls were investigated by identifying the greatest area under the receiver operating curve from a total of 648 possible combinations. The optimal parameters were validated on PD patients. Automatic baseline estimation improved characterization of atonia during REM sleep, as it eliminates inter/intra-observer variability and can be standardized across diagnostic centres. We found an optimized method for quantifying motor activity during REM sleep. The method was stable and can be used to differentiate RBD from controls and to quantify motor activity during REM sleep in patients with neurodegeneration. No control had more than 30% of REM sleep with increased motor activity; patients with known RBD had as low activity as 4.5%. We developed and applied a sensitive, quantitative, automatic algorithm to evaluate loss of atonia in RBD patients.

  8. Arousal responses to added inspiratory resistance during REM and non-REM sleep in normal subjects.

    PubMed Central

    Gugger, M; Bögershausen, S; Schäffler, L

    1993-01-01

    BACKGROUND: Arousal in response to increased airflow resistance during sleep, especially rapid eye movement sleep (REM), could be an important protective mechanism against asphyxia. METHODS: The arousal response to the application of an external inspiratory resistance of 25 cm H2O/l/s was determined during REM and non-REM sleep in ten healthy men. RESULTS: The number of arousals occurring within two 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 was similar to that during stage 1. The proportion of arousals to non-arousals decreased significantly from stage 1 to stage 4. The mean time to arousal in REM was significantly shorter than in non-REM stages 1, 2 or 3/4 and increased significantly from stage 1 to 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. CONCLUSIONS: The results show a significantly increased arousal response to an added inspiratory resistive load in REM sleep compared with non-REM sleep stages 2, 3 or 4 in normal men. In the context of previous studies these data could add support to the hypothesis that the decreased arousal response during REM sleep in patients with sleep apnoea might be due to an impairment of the normal "central processing" of this stimulus. PMID:8493624

  9. Control of REM sleep by ventral medulla GABAergic neurons.

    PubMed

    Weber, Franz; Chung, Shinjae; Beier, Kevin T; Xu, Min; Luo, Liqun; Dan, Yang

    2015-10-15

    Rapid eye movement (REM) sleep is a distinct brain state characterized by activated electroencephalogram and complete skeletal muscle paralysis, and is associated with vivid dreams. Transection studies by Jouvet first demonstrated that the brainstem is both necessary and sufficient for REM sleep generation, and the neural circuits in the pons have since been studied extensively. The medulla also contains neurons that are active during REM sleep, but whether they play a causal role in REM sleep generation remains unclear. Here we show that a GABAergic (γ-aminobutyric-acid-releasing) pathway originating from the ventral medulla powerfully promotes REM sleep in mice. Optogenetic activation of ventral medulla GABAergic neurons rapidly and reliably initiated REM sleep episodes and prolonged their durations, whereas inactivating these neurons had the opposite effects. Optrode recordings from channelrhodopsin-2-tagged ventral medulla GABAergic neurons showed that they were most active during REM sleep (REMmax), and during wakefulness they were preferentially active during eating and grooming. Furthermore, dual retrograde tracing showed that the rostral projections to the pons and midbrain and caudal projections to the spinal cord originate from separate ventral medulla neuron populations. Activating the rostral GABAergic projections was sufficient for both the induction and maintenance of REM sleep, which are probably mediated in part by inhibition of REM-suppressing GABAergic neurons in the ventrolateral periaqueductal grey. These results identify a key component of the pontomedullary network controlling REM sleep. The capability to induce REM sleep on command may offer a powerful tool for investigating its functions. PMID:26444238

  10. Control of REM sleep by ventral medulla GABAergic neurons.

    PubMed

    Weber, Franz; Chung, Shinjae; Beier, Kevin T; Xu, Min; Luo, Liqun; Dan, Yang

    2015-10-15

    Rapid eye movement (REM) sleep is a distinct brain state characterized by activated electroencephalogram and complete skeletal muscle paralysis, and is associated with vivid dreams. Transection studies by Jouvet first demonstrated that the brainstem is both necessary and sufficient for REM sleep generation, and the neural circuits in the pons have since been studied extensively. The medulla also contains neurons that are active during REM sleep, but whether they play a causal role in REM sleep generation remains unclear. Here we show that a GABAergic (γ-aminobutyric-acid-releasing) pathway originating from the ventral medulla powerfully promotes REM sleep in mice. Optogenetic activation of ventral medulla GABAergic neurons rapidly and reliably initiated REM sleep episodes and prolonged their durations, whereas inactivating these neurons had the opposite effects. Optrode recordings from channelrhodopsin-2-tagged ventral medulla GABAergic neurons showed that they were most active during REM sleep (REMmax), and during wakefulness they were preferentially active during eating and grooming. Furthermore, dual retrograde tracing showed that the rostral projections to the pons and midbrain and caudal projections to the spinal cord originate from separate ventral medulla neuron populations. Activating the rostral GABAergic projections was sufficient for both the induction and maintenance of REM sleep, which are probably mediated in part by inhibition of REM-suppressing GABAergic neurons in the ventrolateral periaqueductal grey. These results identify a key component of the pontomedullary network controlling REM sleep. The capability to induce REM sleep on command may offer a powerful tool for investigating its functions.

  11. REM sleep dysregulation in depression: state of the art.

    PubMed

    Palagini, Laura; Baglioni, Chiara; Ciapparelli, Antonio; Gemignani, Angelo; Riemann, Dieter

    2013-10-01

    Disturbances of sleep are typical for most depressed patients and belong to the core symptoms of the disorder. Since the 1960s polysomnographic sleep research has demonstrated that besides disturbances of sleep continuity, depression is associated with altered sleep architecture, i.e., a decrease in slow wave sleep (SWS) production and disturbed rapid eye movement (REM) sleep regulation. Shortened REM latency (i.e., the interval between sleep onset and the occurrence of the first REM period), increased REM sleep duration and increased REM density (i.e., the frequency of rapid eye movements per REM period) have been considered as biological markers of depression which might predict relapse and recurrence. High risk studies including healthy relatives of patients with depression demonstrate that REM sleep alterations may precede the clinical expression of depression and may thus be useful in identifying subjects at high risk for the illness. Several models have been developed to explain REM sleep abnormalities in depression, like the cholinergic-aminergic imbalance model or chronobiologically inspired theories, which are reviewed in this overview. Moreover, REM sleep alterations have been recently considered not only as biological "scars" but as true endophenotypes of depression. This review discusses the genetic, neurochemical and neurobiological factors that have been implicated to play a role in the complex relationships between REM sleep and depression. We hypothesize on the one hand that REM sleep dysregulation in depression may be linked to a genetic predisposition/vulnerability to develop the illness; on the other hand it is conceivable that REM sleep disinhibition in itself is a part of a maladaptive stress reaction with increased allostatic load. We also discuss whether the REM sleep changes in depression may contribute themselves to the development of central symptoms of depression such as cognitive distortions including negative self-esteem and the

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

    PubMed

    Takeuchi, T; Miyasita, A; Inugami, M; Yamamoto, Y

    2001-03-01

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

  13. Sleep- and circadian-dependent modulation of REM density.

    PubMed

    Khalsa, Sat Bir S; Conroy, Deirdre A; Duffy, Jeanne F; Czeisler, Charles A; Dijk, Derk-Jan

    2002-03-01

    Rapid eye movement (REM) density, a measure of the frequency of rapid eye movements during REM sleep, is known to increase over the course of the sleep episode. However, the circadian modulation of REM density has not been thoroughly evaluated. Data from a forced desynchrony protocol, in which 20 consecutive sleep opportunities were systematically scheduled over the entire circadian cycle, were analysed. The REM density was evaluated from polysomnographically recorded REM sleep episodes, and analyzed as a function of time in the sleep opportunity and as a function of phase in the circadian cycle. The REM density showed a robust increase over the course of the sleep episode. This sleep-dependent increase was observed regardless of circadian phase, because data analyzed from different thirds of the circadian cycle exhibited a similar pattern. The REM density did not show a significant circadian-dependent modulation for data from the entire sleep opportunity. However, analysis of circadian modulation from separate thirds of the sleep opportunity revealed a significant circadian modulation in the last third of the sleep episode. Maximum REM densities were observed when the last third of the sleep episode coincided with the wake-maintenance zone, i.e.;8-10 h before the crest of the circadian rhythm of REM sleep propensity. These results confirm the dominant sleep-dependent modulation of REM density, and indicate that the density of REMs is greatest when sleep pressure is low, such as in the latter part of the sleep episode, at which time the circadian modulation of REM density is also appreciable.

  14. Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia

    PubMed Central

    Chouchou, Florian; Chauny, Jean-Marc; Rainville, Pierre; Lavigne, Gilles J.

    2015-01-01

    The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated. PMID:26678391

  15. Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia.

    PubMed

    Chouchou, Florian; Chauny, Jean-Marc; Rainville, Pierre; Lavigne, Gilles J

    2015-01-01

    The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.

  16. Correlations using the NREM-REM sleep cycle frequency support distinct regulation mechanisms for REM and NREM sleep.

    PubMed

    Le Bon, O; Staner, L; Rivelli, S K; Hoffmann, G; Pelc, I; Linkowski, P

    2002-07-01

    Polysomnograms of most homeothermic species distinguish two states, rapid eye movement (REM) and non-REM (NREM) sleep. These alternate several times during the night for reasons and following rules that remain poorly understood. It is unknown whether each state has its own function and regulation or whether they represent two facets of the same process. The present study compared the mean REM/NREM sleep ratio and the mean number of NREM-REM sleep cycles across 3 consecutive nights. The rationale was that, if REM and NREM sleep are tightly associated, their ratio should be comparable whatever the cycle frequency in the night. Twenty-six healthy subjects of both sexes were recorded at their home for 4 consecutive nights. The correlation between the REM/NREM sleep ratio and the number of cycles was highly significant. Of the two sleep components, REM sleep was associated to the number of cycles, whereas NREM sleep was not. This suggests that the relationship between REM sleep and NREM sleep is rather weak within cycles, does not support the concept of NREM-REM sleep cycles as miniature units of the sleep process, and favors the concept of distinct mechanisms of regulation for the two components.

  17. Narcolepsy presenting as REM sleep behaviour disorder.

    PubMed

    Bonakis, Anastasios; Howard, Robin S; Williams, Adrian

    2008-05-01

    REM sleep behaviour disorder (RBD) is a neurological condition well known to be associated with the synucleinopathies in middle-aged patients. However, there is much less data concerning its development, evolution, and association with other disorders in younger patients. We report two patients aged less than 33 years who presented with clinical and polysomnographical features of RBD, both of whom proved to have previously undiagnosed narcolepsy. Whilst the association of narcolepsy with RBD has been previously recognised, this is the first report of narcoleptic patients presenting with RBD. Narcolepsy should be included in the differential diagnosis of young patients presenting with abnormal behaviour during sleep compatible with RBD. PMID:18343568

  18. Changes in REM-Sleep Percentage Over the Adult Lifespan

    PubMed Central

    Floyd, Judith A.; Janisse, James J.; Jenuwine, Elizabeth S.; Ager, Joel W.

    2007-01-01

    Study Objectives: To resolve inconsistencies in previously reported changes in percentage of rapid eye movement sleep (REM%) over the adult lifespan and to identify gaps in available information about adults' REM sleep. Design: A research synthesis approach specifically designed to detect nonlinear change. Cubic B smoothing splines were fitted to scatterplots generated from reported means and variance for REM%, REM minutes, and total sleep time. Participants: 382 English-language research reports provided REM% values for 4171 subjects; REM minutes values for 2722 subjects; and values of total sleep time for 5037 subjects. Samples were composed of subjects described by authors as normal or healthy. Mean ages of samples ranged from 18.0 to 91.7 years. Setting: University research center. Interventions: N/A. Measurements and Results: Two coders extracted information. Intercoder reliability was above cutoffs for excellent. Authors often failed to describe screening procedures used to determine subjects' health status. Few results were reported separately for women. The functional relationship between age and REM% was essentially linear over much of the adult lifespan, decreasing about 0.6% per decade. The best estimate of when REM% ceased its small linear decline was the mid-70s, after which time a small increase in REM% was observed due to REM minutes increasing while total sleep time declined. Conclusions: Ability to detect both linear and nonlinear change in REM%, REM minutes, and total sleep time over the lifespan was useful for resolving inconsistent findings about the existence of changes in REM% with aging. This approach to research synthesis also facilitated identification of ages for which little normative information about REM sleep was available. Citation: Floyd JA; Janisse JJ; Jenuwine ES et al. Changes in REM-sleep percentage over the adult lifespan. SLEEP 2007;30(7):829-836. PMID:17682652

  19. Control of REM Sleep by Ventral Medulla GABAergic Neurons

    PubMed Central

    Weber, Franz; Chung, Shinjae; Beier, Kevin T.; Luo, Liqun; Dan, Yang

    2015-01-01

    Rapid eye movement (REM) sleep is a distinct brain state characterized by activated electroencephalogram (EEG) and complete skeletal muscle paralysis, and it is associated with vivid dreams1-3. Transection studies by Jouvet first demonstrated that the brainstem is both necessary and sufficient for REM sleep generation2, and the neural circuits in the pons have since been studied extensively4-8. The medulla also contains neurons that are active during REM sleep9-13, but whether they play a causal role in REM sleep generation remains unclear. Here we show that a GABAergic pathway originating from the ventral medulla (vM) powerfully promotes REM sleep. Optogenetic activation of vM GABAergic neurons rapidly and reliably initiated REM sleep episodes and prolonged their durations, whereas inactivating these neurons had the opposite effects. Optrode recordings from channelrhodopsin 2 (ChR2)-tagged vM GABAergic neurons showed that they were most active during REM sleep (REM-max), and during wakefulness they were preferentially active during eating and grooming. Furthermore, dual retrograde tracing showed that the rostral projections to the pons and midbrain and caudal projections to the spinal cord originate from separate vM neuron populations. Activating the rostral GABAergic projections was sufficient for both the induction and maintenance of REM sleep, which are likely mediated in part by inhibition of REM-suppressing GABAergic neurons in the ventrolateral periaqueductal gray (vlPAG). These results identify a key component of the pontomedullary network controlling REM sleep. The capability to induce REM sleep on command may offer a powerful tool for investigating its functions. PMID:26444238

  20. Brainstem mechanisms of paradoxical (REM) sleep generation.

    PubMed

    Luppi, Pierre-Hervé; Clement, Olivier; Sapin, Emilie; Peyron, Christelle; Gervasoni, Damien; Léger, Lucienne; Fort, Patrice

    2012-01-01

    Paradoxical sleep (PS) is characterized by EEG activation with a disappearance of muscle tone and the occurrence of rapid eye movements (REM) in contrast to slow-wave sleep (SWS, also known as non-REM sleep) identified by the presence of delta waves. Soon after the discovery of PS, it was demonstrated that the structures necessary and sufficient for its genesis are restricted to the brainstem. We review here recent results indicating that brainstem glutamatergic and GABAergic, rather than cholinergic and monoaminergic, neurons play a key role in the genesis of PS. We hypothesize that the entrance to PS from SWS is due to the activation of PS-on glutamatergic neurons localized in the pontine sublaterodorsal tegmental nucleus. The activation of these neurons would be due to a permanent glutamatergic input arising from the lateral and ventrolateral periaqueductal gray (vlPAG) and the removal at the onset of PS of a GABAergic inhibition present during W and SWS. Such inhibition would be coming from PS-off GABAergic neurons localized in the vlPAG and the adjacent deep mesencephalic reticular nucleus. The cessation of activity of these PS-off GABAergic neurons at the onset and during PS would be due to direct projections from intermingled GABAergic PS-on neurons. Activation of PS would depend on the reciprocal interactions between the GABAergic PS-on and PS-off neurons, intrinsic cellular and molecular events, and integration of multiple physiological parameters.

  1. REM Sleep at its Core - Circuits, Neurotransmitters, and Pathophysiology.

    PubMed

    Fraigne, Jimmy J; Torontali, Zoltan A; Snow, Matthew B; Peever, John H

    2015-01-01

    Rapid eye movement (REM) sleep is generated and maintained by the interaction of a variety of neurotransmitter systems in the brainstem, forebrain, and hypothalamus. Within these circuits lies a core region that is active during REM sleep, known as the subcoeruleus nucleus (SubC) or sublaterodorsal nucleus. It is hypothesized that glutamatergic SubC neurons regulate REM sleep and its defining features such as muscle paralysis and cortical activation. REM sleep paralysis is initiated when glutamatergic SubC cells activate neurons in the ventral medial medulla, which causes release of GABA and glycine onto skeletal motoneurons. REM sleep timing is controlled by activity of GABAergic neurons in the ventrolateral periaqueductal gray and dorsal paragigantocellular reticular nucleus as well as melanin-concentrating hormone neurons in the hypothalamus and cholinergic cells in the laterodorsal and pedunculo-pontine tegmentum in the brainstem. Determining how these circuits interact with the SubC is important because breakdown in their communication is hypothesized to underlie narcolepsy/cataplexy and REM sleep behavior disorder (RBD). This review synthesizes our current understanding of mechanisms generating healthy REM sleep and how dysfunction of these circuits contributes to common REM sleep disorders such as cataplexy/narcolepsy and RBD.

  2. REM Sleep at its Core – Circuits, Neurotransmitters, and Pathophysiology

    PubMed Central

    Fraigne, Jimmy J.; Torontali, Zoltan A.; Snow, Matthew B.; Peever, John H.

    2015-01-01

    Rapid eye movement (REM) sleep is generated and maintained by the interaction of a variety of neurotransmitter systems in the brainstem, forebrain, and hypothalamus. Within these circuits lies a core region that is active during REM sleep, known as the subcoeruleus nucleus (SubC) or sublaterodorsal nucleus. It is hypothesized that glutamatergic SubC neurons regulate REM sleep and its defining features such as muscle paralysis and cortical activation. REM sleep paralysis is initiated when glutamatergic SubC cells activate neurons in the ventral medial medulla, which causes release of GABA and glycine onto skeletal motoneurons. REM sleep timing is controlled by activity of GABAergic neurons in the ventrolateral periaqueductal gray and dorsal paragigantocellular reticular nucleus as well as melanin-concentrating hormone neurons in the hypothalamus and cholinergic cells in the laterodorsal and pedunculo-pontine tegmentum in the brainstem. Determining how these circuits interact with the SubC is important because breakdown in their communication is hypothesized to underlie narcolepsy/cataplexy and REM sleep behavior disorder (RBD). This review synthesizes our current understanding of mechanisms generating healthy REM sleep and how dysfunction of these circuits contributes to common REM sleep disorders such as cataplexy/narcolepsy and RBD. PMID:26074874

  3. REM Sleep at its Core - Circuits, Neurotransmitters, and Pathophysiology.

    PubMed

    Fraigne, Jimmy J; Torontali, Zoltan A; Snow, Matthew B; Peever, John H

    2015-01-01

    Rapid eye movement (REM) sleep is generated and maintained by the interaction of a variety of neurotransmitter systems in the brainstem, forebrain, and hypothalamus. Within these circuits lies a core region that is active during REM sleep, known as the subcoeruleus nucleus (SubC) or sublaterodorsal nucleus. It is hypothesized that glutamatergic SubC neurons regulate REM sleep and its defining features such as muscle paralysis and cortical activation. REM sleep paralysis is initiated when glutamatergic SubC cells activate neurons in the ventral medial medulla, which causes release of GABA and glycine onto skeletal motoneurons. REM sleep timing is controlled by activity of GABAergic neurons in the ventrolateral periaqueductal gray and dorsal paragigantocellular reticular nucleus as well as melanin-concentrating hormone neurons in the hypothalamus and cholinergic cells in the laterodorsal and pedunculo-pontine tegmentum in the brainstem. Determining how these circuits interact with the SubC is important because breakdown in their communication is hypothesized to underlie narcolepsy/cataplexy and REM sleep behavior disorder (RBD). This review synthesizes our current understanding of mechanisms generating healthy REM sleep and how dysfunction of these circuits contributes to common REM sleep disorders such as cataplexy/narcolepsy and RBD. PMID:26074874

  4. Endogenous cholinergic input to the pontine REM sleep generator is not required for REM sleep to occur.

    PubMed

    Grace, Kevin P; Vanstone, Lindsay E; Horner, Richard L

    2014-10-22

    Initial theories of rapid eye movement (REM) sleep generation posited that induction of the state required activation of the pontine subceruleus (SubC) by cholinergic inputs. Although the capacity of cholinergic neurotransmission to contribute to REM sleep generation has been established, the role of cholinergic inputs in the generation of REM sleep is ultimately undetermined as the critical test of this hypothesis (local blockade of SubC acetylcholine receptors) has not been rigorously performed. We used bilateral microdialysis in freely behaving rats (n = 32), instrumented for electroencephalographic and electromyographic recording, to locally manipulate neurotransmission in the SubC with select drugs. As predicted, combined microperfusion of D-AP5 (glutamate receptor antagonist) and muscimol (GABAA receptor agonist) in the SubC virtually eliminated REM sleep. However, REM sleep was not reduced by scopolamine microperfusion in this same region, at a concentration capable of blocking the effects of cholinergic receptor stimulation. This result suggests that transmission of REM sleep drive to the SubC is acetylcholine-independent. Although SubC cholinergic inputs are not majorly involved in REM sleep generation, they may perform a minor function in the reinforcement of transitions into REM sleep, as evidenced by increases in non-REM-to-REM sleep transition duration and failure rate during cholinergic receptor blockade. Cholinergic receptor antagonism also attenuated the normal increase in hippocampal θ oscillations that characterize REM sleep. Using computational modeling, we show that our in vivo results are consistent with a mutually excitatory interaction between the SubC and cholinergic neurons where, importantly, cholinergic neuron activation is gated by SubC activity.

  5. Visual short-term memory deficits in REM sleep behaviour disorder mirror those in Parkinson's disease.

    PubMed

    Rolinski, Michal; Zokaei, Nahid; Baig, Fahd; Giehl, Kathrin; Quinnell, Timothy; Zaiwalla, Zenobia; Mackay, Clare E; Husain, Masud; Hu, Michele T M

    2016-01-01

    Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson's disease. Here we examined visual short-term memory deficits--long associated with Parkinson's disease--in patients with REM sleep behaviour disorder without Parkinson's disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson's disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson's disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson's disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson's disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of 'prodromal' Parkinson's disease that might be useful in tracking disease progression and for disease-modifying intervention trials.

  6. Functional Anatomy of Non-REM Sleep

    PubMed Central

    de Andrés, Isabel; Garzón, Miguel; Reinoso-Suárez, Fernando

    2011-01-01

    The state of non-REM sleep (NREM), or slow wave sleep, is associated with a synchronized EEG pattern in which sleep spindles and/or K complexes and high-voltage slow wave activity (SWA) can be recorded over the entire cortical surface. In humans, NREM is subdivided into stages 2 and 3–4 (presently named N3) depending on the proportions of each of these polygraphic events. NREM is necessary for normal physical and intellectual performance and behavior. An overview of the brain structures involved in NREM generation shows that the thalamus and the cerebral cortex are absolutely necessary for the most significant bioelectric and behavioral events of NREM to be expressed; other structures like the basal forebrain, anterior hypothalamus, cerebellum, caudal brain stem, spinal cord and peripheral nerves contribute to NREM regulation and modulation. In NREM stage 2, sustained hyperpolarized membrane potential levels resulting from interaction between thalamic reticular and projection neurons gives rise to spindle oscillations in the membrane potential; the initiation and termination of individual spindle sequences depends on corticothalamic activities. Cortical and thalamic mechanisms are also involved in the generation of EEG delta SWA that appears in deep stage 3–4 (N3) NREM; the cortex has classically been considered to be the structure that generates this activity, but delta oscillations can also be generated in thalamocortical neurons. NREM is probably necessary to normalize synapses to a sustainable basal condition that can ensure cellular homeostasis. Sleep homeostasis depends not only on the duration of prior wakefulness but also on its intensity, and sleep need increases when wakefulness is associated with learning. NREM seems to ensure cell homeostasis by reducing the number of synaptic connections to a basic level; based on simple energy demands, cerebral energy economizing during NREM sleep is one of the prevalent hypotheses to explain NREM homeostasis

  7. Breathing during REM and non-REM sleep: correlated versus uncorrelated behaviour

    NASA Astrophysics Data System (ADS)

    Kantelhardt, Jan W.; Penzel, Thomas; Rostig, Sven; Becker, Heinrich F.; Havlin, Shlomo; Bunde, Armin

    2003-03-01

    Healthy sleep can be characterized by several stages: deep sleep, light sleep, and REM sleep. Here we show that these sleep stages lead to different autonomic regulation of breathing. Using the detrended fluctuation analysis up to the fourth order we find that breath-to-breath intervals and breath volumes separated by several breaths are long-range correlated during the REM stages and during wake states. In contrast, in the non-REM stages (deep sleep and light sleep), long-range correlations are absent. This behaviour is very similar to the correlation behaviour of the heart rate during the night and may be related to the phase synchronization between heartbeat and breathing found recently. We speculate that the differences are caused by different cortically influenced control of the autonomic nervous system.

  8. The role of REM sleep theta activity in emotional memory

    PubMed Central

    Hutchison, Isabel C.; Rathore, Shailendra

    2015-01-01

    While non-REM (NREM) sleep has been strongly implicated in the reactivation and consolidation of memory traces, the role of rapid-eye movement (REM) sleep remains unclear. A growing body of research on humans and animals provide behavioral evidence for a role of REM sleep in the strengthening and modulation of emotional memories. Theta activity—which describes low frequency oscillations in the local field potential within the hippocampus, amygdala and neocortex—is a prominent feature of both wake and REM sleep in humans and rodents. Theta coherence between the hippocampus and amygdala drives large-scale pontine-geniculo-occipital (PGO) waves, the density of which predicts increases in plasticity-related gene expression. This could potentially facilitate the processing of emotional memory traces within the hippocampus during REM sleep. Further, the timing of hippocampal activity in relation to theta phase is vital in determining subsequent potentiation of neuronal activity. This could allow the emotionally modulated strengthening of novel and gradual weakening of consolidated hippocampal memory traces during REM sleep. Hippocampal theta activity is also correlated with REM sleep levels of achetylcholine - which is thought to reduce hippocampal inputs in the neocortex. The additional low levels of noradrenaline during REM sleep, which facilitate feedback within the neocortex, could allow the integration of novel memory traces previously consolidated during NREM sleep. We therefore propose that REM sleep mediates the prioritized processing of emotional memories within the hippocampus, the integration of previously consolidated memory traces within the neocortex, as well as the disengagement of consolidated neocortical memory traces from the hippocampus. PMID:26483709

  9. The role of REM sleep theta activity in emotional memory.

    PubMed

    Hutchison, Isabel C; Rathore, Shailendra

    2015-01-01

    While non-REM (NREM) sleep has been strongly implicated in the reactivation and consolidation of memory traces, the role of rapid-eye movement (REM) sleep remains unclear. A growing body of research on humans and animals provide behavioral evidence for a role of REM sleep in the strengthening and modulation of emotional memories. Theta activity-which describes low frequency oscillations in the local field potential within the hippocampus, amygdala and neocortex-is a prominent feature of both wake and REM sleep in humans and rodents. Theta coherence between the hippocampus and amygdala drives large-scale pontine-geniculo-occipital (PGO) waves, the density of which predicts increases in plasticity-related gene expression. This could potentially facilitate the processing of emotional memory traces within the hippocampus during REM sleep. Further, the timing of hippocampal activity in relation to theta phase is vital in determining subsequent potentiation of neuronal activity. This could allow the emotionally modulated strengthening of novel and gradual weakening of consolidated hippocampal memory traces during REM sleep. Hippocampal theta activity is also correlated with REM sleep levels of achetylcholine - which is thought to reduce hippocampal inputs in the neocortex. The additional low levels of noradrenaline during REM sleep, which facilitate feedback within the neocortex, could allow the integration of novel memory traces previously consolidated during NREM sleep. We therefore propose that REM sleep mediates the prioritized processing of emotional memories within the hippocampus, the integration of previously consolidated memory traces within the neocortex, as well as the disengagement of consolidated neocortical memory traces from the hippocampus. PMID:26483709

  10. The role of REM sleep theta activity in emotional memory.

    PubMed

    Hutchison, Isabel C; Rathore, Shailendra

    2015-01-01

    While non-REM (NREM) sleep has been strongly implicated in the reactivation and consolidation of memory traces, the role of rapid-eye movement (REM) sleep remains unclear. A growing body of research on humans and animals provide behavioral evidence for a role of REM sleep in the strengthening and modulation of emotional memories. Theta activity-which describes low frequency oscillations in the local field potential within the hippocampus, amygdala and neocortex-is a prominent feature of both wake and REM sleep in humans and rodents. Theta coherence between the hippocampus and amygdala drives large-scale pontine-geniculo-occipital (PGO) waves, the density of which predicts increases in plasticity-related gene expression. This could potentially facilitate the processing of emotional memory traces within the hippocampus during REM sleep. Further, the timing of hippocampal activity in relation to theta phase is vital in determining subsequent potentiation of neuronal activity. This could allow the emotionally modulated strengthening of novel and gradual weakening of consolidated hippocampal memory traces during REM sleep. Hippocampal theta activity is also correlated with REM sleep levels of achetylcholine - which is thought to reduce hippocampal inputs in the neocortex. The additional low levels of noradrenaline during REM sleep, which facilitate feedback within the neocortex, could allow the integration of novel memory traces previously consolidated during NREM sleep. We therefore propose that REM sleep mediates the prioritized processing of emotional memories within the hippocampus, the integration of previously consolidated memory traces within the neocortex, as well as the disengagement of consolidated neocortical memory traces from the hippocampus.

  11. Pontine regulation of REM sleep components in cats: integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep.

    PubMed

    Shouse, M N; Siegel, J M

    1992-01-31

    Transection, lesion and unit recording studies have localized rapid eye movement (REM) sleep mechanisms to the pons. Recent work has emphasized the role of pontine cholinergic cells, especially those of the pedunculopontine tegmentum (PPT). The present study differentiated REM sleep deficits associated with lesions of the PPT from other pontine regions implicated in REM sleep generation, including those with predominantly cholinergic vs non-cholinergic cells. Twelve hour polygraphic recordings were obtained in 18 cats before and 1-2 weeks after bilateral electrolytic or radio frequency lesions of either: (1) PPT, which contains the dorsolateral pontine cholinergic cell column; (2) laterodorsal tegmental nucleus (LDT), which contains the dorsomedial pontine cholinergic cell column; (3) locus ceruleus (LC), which contains mostly noradrenergic cells; or (4) subceruleus (LC alpha, peri-LC alpha and the lateral tegmental field), which also contains predominantly noncholinergic cells. There were three main findings: (i) Only lesions of PPT and subceruleus significantly affected REM sleep time. These lesions produced comparable reductions in REM sleep time but influenced REM sleep components quite differently: (ii) PPT lesions, estimated to damage 90 +/- 4% of cholinergic cells, reduced the number of REM sleep entrances and phasic events, including ponto-geniculooccipital (PGO) spikes and rapid eye movements (REMs), but did not prevent complete atonia during REM sleep: (iii) Subceruleus lesions eliminated atonia during REM sleep. Mobility appeared to arouse the cat prematurely from REM sleep and may explain the brief duration of REM sleep epochs seen exclusively in this group. Despite the reduced amount of REM sleep, the total number of PGO spikes and REM sleep entrances increased over baseline values. Collectively, the results distinguish pontine loci regulating phasic events vs atonia. PPT lesions reduced phasic events, whereas subceruleus lesions created REM sleep

  12. Carbachol models of REM sleep: recent developments and new directions.

    PubMed

    Kubin, L

    2001-02-01

    Since the early '60s, injections of a broad-spectrum muscarinic cholinergic agonist, carbachol, into the medial pontine reticular formation (mPRF) of cats have been extensively used as a tool with which to study the neural mechanisms of rapid eye movement (REM) sleep. During the last decade, new carbachol models of REM sleep were introduced, including chronically instrumented/behaving rats and "reduced" preparations such as decerebrate or anesthetized cats and rats. The combined results from these distinct models show interspecies similarities and differences. The dual nature, both REM sleep-promoting and wakefulness (or arousal)-promoting, of the cholinergic effects exerted within the mPRF is more strongly expressed in rats than in cats. This strengthens the possibility suggested by earlier central neuronal recordings that active wakefulness and REM sleep have extensive common neuronal substrates, and may have evolved from a common behavioral state. Carbachol studies using different intact and reduced models also suggest that powerful REM sleep episode-terminating effects originate in suprapontine structures. In contrast, the timing of REM sleep-like episodes in decerebrate models is determined by a pontomedullary neuronal network responsible for the generation of an ultradian cycle similar to the basic rest-activity cycle of N. Kleitman. Other presumed species differences, such as the more widespread distribution of carbachol-sensitive sites or the relative failure of carbachol to increase the duration of REM sleep episodes in rats when compared to cats, may be of a quantitative or technical nature. While carbachol and many other neurotransmitters and peptides microinjected into the mPRF evoke, enhance or suppress REM sleep, the most sensitive site(s) of their actions have not been fully mapped, and the nature of the cellular and neurochemical interactions taking place at the sites where carbachol triggers the REM sleep-like state remain largely unknown

  13. The Neurobiological Mechanisms and Treatments of REM Sleep Disturbances in Depression

    PubMed Central

    Wang, Yi-Qun; Li, Rui; Zhang, Meng-Qi; Zhang, Ze; Qu, Wei-Min; Huang, Zhi-Li

    2015-01-01

    Most depressed patients suffer from sleep abnormalities, which are one of the critical symptoms of depression. They are robust risk factors for the initiation and development of depression. Studies about sleep electroencephalograms have shown characteristic changes in depression such as reductions in non-rapid eye movement sleep production, disruptions of sleep continuity and disinhibition of rapid eye movement (REM) sleep. REM sleep alterations include a decrease in REM sleep latency, an increase in REM sleep duration and REM sleep density with respect to depressive episodes. Emotional brain processing dependent on the normal sleep-wake regulation seems to be failed in depression, which also promotes the development of clinical depression. Also, REM sleep alterations have been considered as biomarkers of depression. The disturbances of norepinephrine and serotonin systems may contribute to REM sleep abnormalities in depression. Lastly, this review also discusses the effects of different antidepressants on REM sleep disturbances in depression. PMID:26412074

  14. The Neurobiological Mechanisms and Treatments of REM Sleep Disturbances in Depression.

    PubMed

    Wang, Yi-Qun; Li, Rui; Zhang, Meng-Qi; Zhang, Ze; Qu, Wei-Min; Huang, Zhi-Li

    2015-01-01

    Most depressed patients suffer from sleep abnormalities, which are one of the critical symptoms of depression. They are robust risk factors for the initiation and development of depression. Studies about sleep electroencephalograms have shown characteristic changes in depression such as reductions in non-rapid eye movement sleep production, disruptions of sleep continuity and disinhibition of rapid eye movement (REM) sleep. REM sleep alterations include a decrease in REM sleep latency, an increase in REM sleep duration and REM sleep density with respect to depressive episodes. Emotional brain processing dependent on the normal sleep-wake regulation seems to be failed in depression, which also promotes the development of clinical depression. Also, REM sleep alterations have been considered as biomarkers of depression. The disturbances of norepinephrine and serotonin systems may contribute to REM sleep abnormalities in depression. Lastly, this review also discusses the effects of different antidepressants on REM sleep disturbances in depression.

  15. Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep.

    PubMed

    Van Dort, Christa J; Zachs, Daniel P; Kenny, Jonathan D; Zheng, Shu; Goldblum, Rebecca R; Gelwan, Noah A; Ramos, Daniel M; Nolan, Michael A; Wang, Karen; Weng, Feng-Ju; Lin, Yingxi; Wilson, Matthew A; Brown, Emery N

    2015-01-13

    Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.

  16. Slow waves, sharp waves, ripples, and REM in sleeping dragons.

    PubMed

    Shein-Idelson, Mark; Ondracek, Janie M; Liaw, Hua-Peng; Reiter, Sam; Laurent, Gilles

    2016-04-29

    Sleep has been described in animals ranging from worms to humans. Yet the electrophysiological characteristics of brain sleep, such as slow-wave (SW) and rapid eye movement (REM) activities, are thought to be restricted to mammals and birds. Recording from the brain of a lizard, the Australian dragon Pogona vitticeps, we identified SW and REM sleep patterns, thus pushing back the probable evolution of these dynamics at least to the emergence of amniotes. The SW and REM sleep patterns that we observed in lizards oscillated continuously for 6 to 10 hours with a period of ~80 seconds. The networks controlling SW-REM antagonism in amniotes may thus originate from a common, ancient oscillator circuit. Lizard SW dynamics closely resemble those observed in rodent hippocampal CA1, yet they originate from a brain area, the dorsal ventricular ridge, that has no obvious hodological similarity with the mammalian hippocampus. PMID:27126045

  17. Slow waves, sharp waves, ripples, and REM in sleeping dragons.

    PubMed

    Shein-Idelson, Mark; Ondracek, Janie M; Liaw, Hua-Peng; Reiter, Sam; Laurent, Gilles

    2016-04-29

    Sleep has been described in animals ranging from worms to humans. Yet the electrophysiological characteristics of brain sleep, such as slow-wave (SW) and rapid eye movement (REM) activities, are thought to be restricted to mammals and birds. Recording from the brain of a lizard, the Australian dragon Pogona vitticeps, we identified SW and REM sleep patterns, thus pushing back the probable evolution of these dynamics at least to the emergence of amniotes. The SW and REM sleep patterns that we observed in lizards oscillated continuously for 6 to 10 hours with a period of ~80 seconds. The networks controlling SW-REM antagonism in amniotes may thus originate from a common, ancient oscillator circuit. Lizard SW dynamics closely resemble those observed in rodent hippocampal CA1, yet they originate from a brain area, the dorsal ventricular ridge, that has no obvious hodological similarity with the mammalian hippocampus.

  18. Neuroscience: A Distributed Neural Network Controls REM Sleep.

    PubMed

    Peever, John; Fuller, Patrick M

    2016-01-11

    How does the brain control dreams? New science shows that a small node of cells in the medulla - the most primitive part of the brain - may function to control REM sleep, the brain state that underlies dreaming. PMID:26766231

  19. Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep.

    PubMed

    Cooper, Denise C; Ziegler, Michael G; Milic, Milos S; Ancoli-Israel, Sonia; Mills, Paul J; Loredo, José S; Von Känel, Roland; Dimsdale, Joel E

    2014-02-01

    Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain the following measures: slow wave sleep, percentage rapid eye movement (REM) sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and follow-up multiple regressions examined how FMD related to subjective (i.e., Pittsburgh Sleep Quality Index scores) and objective (i.e., polysomnography-derived) indicators of sleep quality. After FMD showed bivariate correlations with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency, further examination with separate regression models indicated that these associations remained significant after adjustments for sex, age, race, hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps < 0.05). Specifically, as FMD decreased, scores on the Pittsburgh Sleep Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps < 0.05). Poorer subjective sleep quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease.

  20. Overnight improvements in two REM sleep-sensitive tasks are associated with both REM and NREM sleep changes, sleep spindle features, and awakenings for dream recall.

    PubMed

    Nielsen, T; O'Reilly, C; Carr, M; Dumel, G; Godin, I; Solomonova, E; Lara-Carrasco, J; Blanchette-Carrière, C; Paquette, T

    2015-07-01

    Memory consolidation is associated with sleep physiology but the contribution of specific sleep stages remains controversial. To clarify the contribution of REM sleep, participants were administered two REM sleep-sensitive tasks to determine if associated changes occurred only in REM sleep. Twenty-two participants (7 men) were administered the Corsi Block Tapping and Tower of Hanoi tasks prior to and again after a night of sleep. Task improvers and non-improvers were compared for sleep structure, sleep spindles, and dream recall. Control participants (N = 15) completed the tasks twice during the day without intervening sleep. Overnight Corsi Block improvement was associated with more REM sleep whereas Tower of Hanoi improvement was associated with more N2 sleep. Corsi Block improvement correlated positively with %REM sleep and Tower of Hanoi improvement with %N2 sleep. Post-hoc analyses suggest Tower of Hanoi effects-but not Corsi Block effects-are due to trait differences. Sleep spindle density was associated with Tower of Hanoi improvement whereas spindle amplitude correlated with Corsi Block improvement. Number of REM awakenings for dream reporting (but not dream recall per se) was associated with Corsi Block, but not Tower of Hanoi, improvement but was confounded with REM sleep time. This non-replication of one of 2 REM-sensitive task effects challenges both 'dual-process' and 'sequential' or 'sleep organization' models of sleep-dependent learning and points rather to capacity limitations on REM sleep. Experimental awakenings for sampling dream mentation may not perturb sleep-dependent learning effects; they may even enhance them. PMID:25291630

  1. Overnight improvements in two REM sleep-sensitive tasks are associated with both REM and NREM sleep changes, sleep spindle features, and awakenings for dream recall.

    PubMed

    Nielsen, T; O'Reilly, C; Carr, M; Dumel, G; Godin, I; Solomonova, E; Lara-Carrasco, J; Blanchette-Carrière, C; Paquette, T

    2015-07-01

    Memory consolidation is associated with sleep physiology but the contribution of specific sleep stages remains controversial. To clarify the contribution of REM sleep, participants were administered two REM sleep-sensitive tasks to determine if associated changes occurred only in REM sleep. Twenty-two participants (7 men) were administered the Corsi Block Tapping and Tower of Hanoi tasks prior to and again after a night of sleep. Task improvers and non-improvers were compared for sleep structure, sleep spindles, and dream recall. Control participants (N = 15) completed the tasks twice during the day without intervening sleep. Overnight Corsi Block improvement was associated with more REM sleep whereas Tower of Hanoi improvement was associated with more N2 sleep. Corsi Block improvement correlated positively with %REM sleep and Tower of Hanoi improvement with %N2 sleep. Post-hoc analyses suggest Tower of Hanoi effects-but not Corsi Block effects-are due to trait differences. Sleep spindle density was associated with Tower of Hanoi improvement whereas spindle amplitude correlated with Corsi Block improvement. Number of REM awakenings for dream reporting (but not dream recall per se) was associated with Corsi Block, but not Tower of Hanoi, improvement but was confounded with REM sleep time. This non-replication of one of 2 REM-sensitive task effects challenges both 'dual-process' and 'sequential' or 'sleep organization' models of sleep-dependent learning and points rather to capacity limitations on REM sleep. Experimental awakenings for sampling dream mentation may not perturb sleep-dependent learning effects; they may even enhance them.

  2. Human REM sleep: influence on feeding behaviour, with clinical implications.

    PubMed

    Horne, James A

    2015-08-01

    Rapid eye movement (REM) sleep shares many underlying mechanisms with wakefulness, to a much greater extent than does non-REM, especially those relating to feeding behaviours, appetite, curiosity, exploratory (locomotor) activities, as well as aspects of emotions, particularly 'fear extinction'. REM is most evident in infancy, thereafter declining in what seems to be a dispensable manner that largely reciprocates increasing wakefulness. However, human adults retain more REM than do other mammals, where for us it is most abundant during our usual final REM period (fREMP) of the night, nearing wakefulness. The case is made that our REM is unusual, and that (i) fREMP retains this 'dispensability', acting as a proxy for wakefulness, able to be forfeited (without REM rebound) and substituted by physical activity (locomotion) when pressures of wakefulness increase; (ii) REM's atonia (inhibited motor output) may be a proxy for this locomotion; (iii) our nocturnal sleep typically develops into a physiological fast, especially during fREMP, which is also an appetite suppressant; (iv) REM may have 'anti-obesity' properties, and that the loss of fREMP may well enhance appetite and contribute to weight gain ('overeating') in habitually short sleepers; (v) as we also select foods for their hedonic (emotional) values, REM may be integral to developing food preferences and dislikes; and (vii) REM seems to have wider influences in regulating energy balance in terms of exercise 'substitution' and energy (body heat) retention. Avenues for further research are proposed, linking REM with feeding behaviours, including eating disorders, and effects of REM-suppressant medications.

  3. The utility of respiratory inductance plethysmography in REM sleep scoring during multiple sleep latency testing.

    PubMed

    Drakatos, Panagis; Higgins, Sean; Duncan, Iain; Bridle, Kate; Briscoe, Sam; Leschziner, Guy D; Kent, Brian D; Williams, Adrian J

    2016-08-01

    Rapid eye movement sleep (REM) presents with a characteristic erratic breathing pattern. We investigated the feasibility of using respiration, derived from respiratory inductance plethysmography (RIP), in conjunction with chin electromyography, electrocardiography and pulse oximetry to facilitate the identification of REM sleep (RespREM) during nocturnal polysomnography (NPSG) and Multiple Sleep Latency Testing (MSLT). The Cohen's weighted kappa for the presence of REM and its duration in 20 consecutive NPSGs, using RespREM and compared to the current guidelines, ranged between 0.74-0.93 and 0.68-0.73 respectively for 5 scorers. The respective intraclass correlation coefficients were above 0.89. In 97.7% of the Sleep-Onset-REM-Periods (SOREMPs) during 41 consecutive MSLTs with preserved RIP, the RespREM was present and in 46.6% it coincided with the REM onset, while in the majority of the remainder RespREM preceded conventional REM onset. The erratic breathing pattern during REM, derived from RIP, is present and easily recognisable during SOREMPs in the MSLTs and may serve as a useful adjunctive measurement in identifying REM sleep.

  4. REM and delta sleep in anorexia nervosa and bulimia.

    PubMed

    Levy, A B; Dixon, K N; Schmidt, H

    1987-03-01

    Several recent investigations have suggested that neurobiological similarities may exist between patients with eating disorders and those with depression. We performed polysomnograms for two consecutive nights on nine bulimic and six anorectic patients who had no concomitant diagnosis of endogenous depression. The rapid eye movement (REM) latency, REM density, and delta sleep of these subjects on night 2 were compared to those of 10 healthy controls of similar ages. Contrary to reports of shortened REM latency and increased REM density in depressed patients, we did not find significant REM differences between eating disorder patients without endogenous depression and healthy control subjects. Low weight anorectics did appear to have less delta sleep than did controls. These findings do not support the contention that eating disorders are variants of affective disorders.

  5. Endogenous GABA levels in the pontine reticular formation are greater during wakefulness than during REM sleep

    PubMed Central

    Vanini, Giancarlo; Wathen, Bradley L.; Lydic, Ralph; Baghdoyan, Helen A.

    2011-01-01

    Studies using drugs that increase or decrease GABAergic transmission suggest that GABA in the pontine reticular formation (PRF) promotes wakefulness and inhibits rapid eye movement (REM) sleep. Cholinergic transmission in the PRF promotes REM sleep, and levels of endogenous acetylcholine (ACh) in the PRF are significantly greater during REM sleep than during wakefulness or non-REM (NREM) sleep. No previous studies have determined whether levels of endogenous GABA in the PRF vary as a function of sleep and wakefulness. This study tested the hypothesis that GABA levels in cat PRF are greatest during wakefulness and lowest during REM sleep. Extracellular GABA levels were measured during wakefulness, NREM sleep, REM sleep, and the REM sleep-like state (REMNeo) caused by microinjecting neostigmine into the PRF. GABA levels varied significantly as a function of sleep and wakefulness, and decreased significantly below waking levels during REM sleep (−42%) and REMNeo (−63%). The decrease in GABA levels during NREM sleep (22% below waking levels) was not statistically significant. Compared to NREM sleep, GABA levels decreased significantly during REM sleep (−27%) and REMNeo (−52%). Comparisons of REM sleep and REMNeo revealed no differences in GABA levels or cortical EEG power. GABA levels did not vary significantly as a function of dialysis site within the PRF. The inverse relationship between changes in PRF levels of GABA and ACh during REM sleep indicates that low GABAergic tone combined with high cholinergic tone in the PRF contributes to the generation of REM sleep. PMID:21325533

  6. Cerebrovascular Response to Arousal from NREM and REM Sleep

    PubMed Central

    Bangash, Muhammad Fuad; Xie, Ailiang; Skatrud, James B.; Reichmuth, Kevin J.; Barczi, Steven R.; Morgan, Barbara J.

    2008-01-01

    Study Objective: To determine the effect of arousal from sleep on cerebral blood flow velocity (CBFV) in relation to associated ventilatory and systemic hemodynamic changes. Participants: Eleven healthy individuals (6 men, 5 women). Measurements: Pulsed Doppler ultrasonography was used to measure CBFV in the middle cerebral artery with simultaneous measurements of sleep state (EEG, EOG, and EMG), ventilation (inductance plethysmography), heart rate (ECG), and arterial pressure (finger plethysmography). Arousals were induced by auditory tones (range: 40–80 dB; duration: 0.5 sec). Cardiovascular responses were examined beat-by-beat for 30 sec before and 30 sec after auditory tones. Results: During NREM sleep, CBFV declined following arousals (-15% ± 2%; group mean ± SEM) with a nadir at 9 sec after the auditory tone, followed by a gradual return to baseline. Mean arterial pressure (MAP; +20% ± 1%) and heart rate (HR; +17% ± 2%) increased with peaks at 5 and 3 sec after the auditory tone, respectively. Minute ventilation (VE) was increased (+35% ± 10%) for 2 breaths after the auditory tone. In contrast, during REM sleep, CBFV increased following arousals (+15% ± 3%) with a peak at 3 sec. MAP (+17% ± 2%) and HR (+15% ± 2%) increased during arousals from REM sleep with peaks at 5 and 3 sec post tone. VE increased (+16% ± 7%) in a smaller, more sustained manner during arousals from REM sleep. Conclusions: Arousals from NREM sleep transiently reduce CBFV, whereas arousals from REM sleep transiently increase CBFV, despite qualitatively and quantitatively similar increases in MAP, HR, and VE in the two sleep states. Citation: Bangash MF; Xie A; Skatrud JB; Reichmuth KJ; Barczi SR; Morgan BJ. Cerebrovascular response to arousal from NREM and REM sleep. SLEEP 2008;31(3):321-327. PMID:18363307

  7. Cognitive flexibility across the sleep-wake cycle: REM-sleep enhancement of anagram problem solving.

    PubMed

    Walker, Matthew P; Liston, Conor; Hobson, J Allan; Stickgold, Robert

    2002-11-01

    Flexible or 'fluid' cognitive processes are regarded as fundamental to problem solving and creative ability, requiring a specific neurophysiological milieu. REM-sleep dreaming is associated with creative processes and abstract reasoning with increased strength of weak associations in cognitive networks. REM sleep is also mediated by a distinctive neurophysiological profile, different to that of wake and NREM sleep. This study compared the performance of 16 subjects on a test of cognitive flexibility using anagram word puzzles following REM and NREM awakenings across the night, and waking performances during the day. REM awakenings provided a significant 32% advantage in the number of anagrams solved compared with NREM awakenings and was equal to that of wake time trials. Correlations of individual performance profiles suggest that REM sleep may offer a different mode of problem solving compared with wake and NREM. When early and late REM and NREM awakening data were separated, a dissociation was evident, with NREM task performance becoming more REM-like later in the night, while REM performance remained constant. These data suggest that the neurophysiology of REM sleep represents a brain state more amenable to flexible cognitive processing than NREM and different from that in wake, and may offer insights into the neurocognitive properties of REM-sleep dreaming.

  8. A Single-Question Screen for REM Sleep Behavior Disorder: A Multicenter Validation Study

    PubMed Central

    Postuma, Ronald B.; Arnulf, Isabelle; Hogl, Birgit; Iranzo, Alex; Miyamoto, Tomoyuki; Dauvilliers, Yves; Oertel, Wolfgang; Ju, Yo-El; Puligheddu, Monica; Jennum, Poul; Pelletier, Amelie; Wolfson, Christina; Leu-Semenescu, Smaranda; Frauscher, Birgit; Miyamoto, Masayuki; De Cock, Valerie Cochen; Unger, Marcus M.; Stiasny-Kolster, Karin; Fantini, Maria Livia; Montplaisir, Jacques Y.

    2014-01-01

    Background Idiopathic REM sleep behavior disorder (RBD) is a parasomnia that is an important risk factor for PD and Lewy body dementia. Its prevalence is unknown. One barrier to determining prevalence is that current screening tools are too long for large-scale epidemiologic surveys. Therefore, we designed the REM Sleep Behavior Disorder Single-Question Screen (RBD1Q), a screening question for dream enactment with a simple yes/no response. Methods Four hundred and eighty-four sleep-clinic– based participants (242 idiopathic RBD patients and 242 controls) completed the screen during a multicenter case-control study. All participants underwent a polysomnogram to define gold-standard diagnosis according to standard criteria. Results We found a sensitivity of 93.8% and a specificity of 87.2%. Sensitivity and specificity were similar in healthy volunteers, compared to controls or patients, with other sleep diagnoses. Conclusions A single-question screen for RBD may reliably detect disease, with psychometric properties favorably comparable to those reported for longer questionnaires. PMID:22729987

  9. Why does serotonergic activity drastically decrease during REM sleep?

    PubMed

    Sato, Kohji

    2013-10-01

    Here, I postulate two hypotheses that can explain the missing link between sleep and the serotonergic system in terms of spine homeostasis and memory consolidation. As dendritic spines contain many kinds of serotonin receptors, and the activation of serotonin receptors generally increases the number of spines in the cortex and hippocampus, I postulate that serotonin neurons are down-regulated during sleep to decrease spine number, which consequently maintains the total spine number at a constant level. Furthermore, since synaptic consolidation during REM sleep needs long-term potentiation (LTP), and serotonin is reported to inhibit LTP in the cortex, I postulate that serotonergic activity must drastically decrease during REM sleep to induce LTP and do memory consolidation. Until now, why serotonergic neurons show these dramatic changes in the sleep-wake cycle remains unexplained; however, making these hypotheses, I can confer physiological meanings on these dramatic changes of serotonergic neurons in terms of spine homeostasis and memory consolidation.

  10. Cold Exposure and Sleep in the Rat: REM Sleep Homeostasis and Body Size

    PubMed Central

    Amici, Roberto; Cerri, Matteo; Ocampo-Garcés, Adrian; Baracchi, Francesca; Dentico, Daniela; Jones, Christine Ann; Luppi, Marco; Perez, Emanuele; Parmeggiani, Pier Luigi; Zamboni, Giovanni

    2008-01-01

    Study Objectives: Exposure to low ambient temperature (Ta) depresses REM sleep (REMS) occurrence. In this study, both short and long-term homeostatic aspects of REMS regulation were analyzed during cold exposure and during subsequent recovery at Ta 24°C. Design: EEG activity, hypothalamic temperature, and motor activity were studied during a 24-h exposure to Tas ranging from 10°C to −10°C and for 4 days during recovery. Setting: Laboratory of Physiological Regulation during the Wake-Sleep Cycle, Department of Human and General Physiology, Alma Mater Studiorum-University of Bologna. Subjects: 24 male albino rats. Interventions: Animals were implanted with electrodes for EEG recording and a thermistor to measure hypothalamic temperature. Measurements and Results: REMS occurrence decreased proportionally with cold exposure, but a fast compensatory REMS rebound occurred during the first day of recovery when the previous loss went beyond a “fast rebound” threshold corresponding to 22% of the daily REMS need. A slow REMS rebound apparently allowed the animals to fully restore the previous REMS loss during the following 3 days of recovery. Conclusion: Comparing the present data on rats with data from earlier studies on cats and humans, it appears that small mammals have less tolerance for REMS loss than large ones. In small mammals, this low tolerance may be responsible on a short-term basis for the shorter wake-sleep cycle, and on long-term basis, for the higher percentage of REMS that is quickly recovered following REMS deprivation. Citation: Amici R; Cerri M; Ocampo-Garcés A; Baracchi F; Dentico D; Jones CA; Luppi M; Perez E; Parmeggiani PL; Zamboni G. Cold exposure and sleep in the rat: REM sleep homeostasis and body size. SLEEP 2008;31(5):708–715. PMID:18517040

  11. Increases in cAMP, MAPK activity, and CREB phosphorylation during REM sleep: implications for REM sleep and memory consolidation.

    PubMed

    Luo, Jie; Phan, Trongha X; Yang, Yimei; Garelick, Michael G; Storm, Daniel R

    2013-04-10

    The cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and cAMP response element-binding protein (CREB) transcriptional pathway is required for consolidation of hippocampus-dependent memory. In mice, this pathway undergoes a circadian oscillation required for memory persistence that reaches a peak during the daytime. Because mice exhibit polyphasic sleep patterns during the day, this suggested the interesting possibility that cAMP, MAPK activity, and CREB phosphorylation may be elevated during sleep. Here, we report that cAMP, phospho-p44/42 MAPK, and phospho-CREB are higher in rapid eye movement (REM) sleep compared with awake mice but are not elevated in non-REM sleep. This peak of activity during REM sleep does not occur in mice lacking calmodulin-stimulated adenylyl cyclases, a mouse strain that learns but cannot consolidate hippocampus-dependent memory. We conclude that a preferential increase in cAMP, MAPK activity, and CREB phosphorylation during REM sleep may contribute to hippocampus-dependent memory consolidation. PMID:23575844

  12. Visual short-term memory deficits in REM sleep behaviour disorder mirror those in Parkinson’s disease

    PubMed Central

    Rolinski, Michal; Baig, Fahd; Giehl, Kathrin; Quinnell, Timothy; Zaiwalla, Zenobia; Mackay, Clare E.; Husain, Masud; Hu, Michele T. M.

    2016-01-01

    Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson’s disease. Here we examined visual short-term memory deficits—long associated with Parkinson’s disease—in patients with REM sleep behaviour disorder without Parkinson’s disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson’s disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson’s disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson’s disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson’s disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of ‘prodromal’ Parkinson’s disease that might be useful in tracking disease progression and for disease-modifying intervention trials. PMID:26582557

  13. REM sleep abnormalities in severe athetoid cerebral palsy.

    PubMed

    Hayashi, M; Inoue, Y; Iwakawa, Y; Sasaki, H

    1990-01-01

    Various abnormalities of sleep have been reported in extrapyramidal diseases in adults. We have investigated the disturbances of REM sleep (SREM) in severe athetoid cerebral palsy (ACP) originating perinatally. Ten ACP patients, 5 males and 5 females ranging from 15 to 30 years old, were studied by means of all-night polygraphic examination. Three cases showed a marked decrease in rapid eye movements in SREM. Moreover, the tone of submental muscle in SREM was also disturbed in three. Regarding body movements during sleep, gross movements and twitch movements of the submental muscle were analyzed. In most of the patients, an abnormal distribution of body movements according to sleep stages was observed, the rate being significantly reduced in SREM. REMs, atonia and body movements are considered to be related to the brainstem function in animals. The results of the present study suggest that perinatal extrapyramidal diseases could also coincide with brainstem dysfunctions.

  14. Coupled Flip-Flop Model for REM Sleep Regulation in the Rat

    PubMed Central

    Dunmyre, Justin R.; Mashour, George A.; Booth, Victoria

    2014-01-01

    Recent experimental studies investigating the neuronal regulation of rapid eye movement (REM) sleep have identified mutually inhibitory synaptic projections among REM sleep-promoting (REM-on) and REM sleep-inhibiting (REM-off) neuronal populations that act to maintain the REM sleep state and control its onset and offset. The control mechanism of mutually inhibitory synaptic interactions mirrors the proposed flip-flop switch for sleep-wake regulation consisting of mutually inhibitory synaptic projections between wake- and sleep-promoting neuronal populations. While a number of synaptic projections have been identified between these REM-on/REM-off populations and wake/sleep-promoting populations, the specific interactions that govern behavioral state transitions have not been completely determined. Using a minimal mathematical model, we investigated behavioral state transition dynamics dictated by a system of coupled flip-flops, one to control transitions between wake and sleep states, and another to control transitions into and out of REM sleep. The model describes the neurotransmitter-mediated inhibitory interactions between a wake- and sleep-promoting population, and between a REM-on and REM-off population. We proposed interactions between the wake/sleep and REM-on/REM-off flip-flops to replicate the behavioral state statistics and probabilities of behavioral state transitions measured from experimental recordings of rat sleep under ad libitum conditions and after 24 h of REM sleep deprivation. Reliable transitions from REM sleep to wake, as dictated by the data, indicated the necessity of an excitatory projection from the REM-on population to the wake-promoting population. To replicate the increase in REM-wake-REM transitions observed after 24 h REM sleep deprivation required that this excitatory projection promote transient activation of the wake-promoting population. Obtaining the reliable wake-nonREM sleep transitions observed in the data required that

  15. Coupled flip-flop model for REM sleep regulation in the rat.

    PubMed

    Dunmyre, Justin R; Mashour, George A; Booth, Victoria

    2014-01-01

    Recent experimental studies investigating the neuronal regulation of rapid eye movement (REM) sleep have identified mutually inhibitory synaptic projections among REM sleep-promoting (REM-on) and REM sleep-inhibiting (REM-off) neuronal populations that act to maintain the REM sleep state and control its onset and offset. The control mechanism of mutually inhibitory synaptic interactions mirrors the proposed flip-flop switch for sleep-wake regulation consisting of mutually inhibitory synaptic projections between wake- and sleep-promoting neuronal populations. While a number of synaptic projections have been identified between these REM-on/REM-off populations and wake/sleep-promoting populations, the specific interactions that govern behavioral state transitions have not been completely determined. Using a minimal mathematical model, we investigated behavioral state transition dynamics dictated by a system of coupled flip-flops, one to control transitions between wake and sleep states, and another to control transitions into and out of REM sleep. The model describes the neurotransmitter-mediated inhibitory interactions between a wake- and sleep-promoting population, and between a REM-on and REM-off population. We proposed interactions between the wake/sleep and REM-on/REM-off flip-flops to replicate the behavioral state statistics and probabilities of behavioral state transitions measured from experimental recordings of rat sleep under ad libitum conditions and after 24 h of REM sleep deprivation. Reliable transitions from REM sleep to wake, as dictated by the data, indicated the necessity of an excitatory projection from the REM-on population to the wake-promoting population. To replicate the increase in REM-wake-REM transitions observed after 24 h REM sleep deprivation required that this excitatory projection promote transient activation of the wake-promoting population. Obtaining the reliable wake-nonREM sleep transitions observed in the data required that

  16. Pramipexole in the treatment of REM sleep behaviour disorder: A critical review.

    PubMed

    Tan, Shian Ming; Wan, Yi Min

    2016-09-30

    While widely accepted as a first-line treatment for rapid eye movement sleep (REM) behaviour disorder, clonazepam (CNZP) has side effects that limit its applicability. Pramipexole is a possible alternative, but limited literature on its effectiveness exists. This review aims to summarize the available data on the use of pramipexole in REM sleep behaviour disorder. A systematic search of major databases was conducted to look for published and on-going trials. This search yielded a total of five articles, all of which are observational in nature. Factors associated with effectiveness include low doses (less than 1.5mg/day) and idiopathic rapid eye movement sleep behaviour disorder/absence of neurodegenerative disease. Overall, the evidence is inconclusive. This is due to the lack of randomised controlled trials and the challenges in interpreting polysomgraphy findings in rapid eye movement sleep behaviour disorder. Suggestions are given on how future trials evaluating pramipexole treatment in rapid eye movement sleep behaviour disorder could overcome current methodological issues in extant literature. PMID:27449005

  17. Pramipexole in the treatment of REM sleep behaviour disorder: A critical review.

    PubMed

    Tan, Shian Ming; Wan, Yi Min

    2016-09-30

    While widely accepted as a first-line treatment for rapid eye movement sleep (REM) behaviour disorder, clonazepam (CNZP) has side effects that limit its applicability. Pramipexole is a possible alternative, but limited literature on its effectiveness exists. This review aims to summarize the available data on the use of pramipexole in REM sleep behaviour disorder. A systematic search of major databases was conducted to look for published and on-going trials. This search yielded a total of five articles, all of which are observational in nature. Factors associated with effectiveness include low doses (less than 1.5mg/day) and idiopathic rapid eye movement sleep behaviour disorder/absence of neurodegenerative disease. Overall, the evidence is inconclusive. This is due to the lack of randomised controlled trials and the challenges in interpreting polysomgraphy findings in rapid eye movement sleep behaviour disorder. Suggestions are given on how future trials evaluating pramipexole treatment in rapid eye movement sleep behaviour disorder could overcome current methodological issues in extant literature.

  18. Morning REM Sleep Naps Facilitate Broad Access to Emotional Semantic Networks

    PubMed Central

    Carr, Michelle; Nielsen, Tore

    2015-01-01

    Study Objectives: The goals of the study were to assess semantic priming to emotion and nonemotion cue words using a novel measure of associational breadth for participants who either took rapid eye movement (REM) or nonrapid eye movement (NREM) naps or who remained awake, and to assess the relation of priming to REM sleep consolidation and REM sleep inertia effects. Design: The associational breadth task was applied in both a priming condition, where cue words were signaled to be memorized prior to sleep (primed), and a nonpriming condition, where cue words were not memorized (nonprimed). Cue words were either emotional (positive, negative) or nonemotional. Participants were randomly assigned to either an awake (WAKE) or a sleep condition, which was subsequently split into NREM or REM groups depending on stage at awakening. Setting: Hospital-based sleep laboratory. Participants: Fifty-eight healthy participants (22 male) ages 18 to 35 y (mean age = 23.3 ± 4.08 y). Measurements and Results: The REM group scored higher than the NREM or WAKE groups on primed, but not nonprimed emotional cue words; the effect was stronger for positive than for negative cue words. However, REM time and percent correlated negatively with degree of emotional priming. Priming occurred for REM awakenings but not for NREM awakenings, even when the latter sleep episodes contained some REM sleep. Conclusions: Associational breadth may be selectively consolidated during REM sleep for stimuli that have been tagged as important for future memory retrieval. That priming decreased with REM time and was higher only for REM sleep awakenings is consistent with two explanatory REM sleep processes: REM sleep consolidation serving emotional downregulation and REM sleep inertia. Citation: Carr M, Nielsen T. Morning REM sleep naps facilitate broad access to emotional semantic networks. SLEEP 2015;38(3):433–443. PMID:25409100

  19. Schema-conformant memories are preferentially consolidated during REM sleep.

    PubMed

    Durrant, Simon J; Cairney, Scott A; McDermott, Cathal; Lewis, Penelope A

    2015-07-01

    Memory consolidation is most commonly described by the standard model, which proposes an initial binding role for the hippocampus which diminishes over time as intracortical connections are strengthened. Recent evidence suggests that slow wave sleep (SWS) plays an essential role in this process. Existing animal and human studies have suggested that memories which fit tightly into an existing knowledge framework or schema might use an alternative consolidation route in which the medial prefrontal cortex takes on the binding role. In this study we sought to investigate the role of sleep in this process using a novel melodic memory task. Participants were asked to remember 32 melodies, half of which conformed to a tonal schema present in all enculturated listeners, and half of which did not fit with this schema. After a 24-h consolidation interval, participants were asked to remember a further 32 melodies, before being given a recognition test in which melodies from both sessions were presented alongside some previously unheard foils. Participants remembered schema-conformant melodies better than non-conformant ones. This was much more strongly the case for consolidated melodies, suggesting that consolidation over a 24-h period preferentially consolidated schema-conformant items. Overnight sleep was monitored between the sessions, and the extent of the consolidation benefit for schema-conformant items was associated with both the amount of REM sleep obtained and EEG theta power in frontal and central regions during REM sleep. Overall our data suggest that REM sleep plays a crucial role in the rapid consolidation of schema-conformant items. This finding is consistent with previous results from animal studies and the SLIMM model of Van Kesteren, Ruiter, Fernández, and Henson (2012), and suggest that REM sleep, rather than SWS, may be involved in an alternative pathway of consolidation for schema-conformant memories. PMID:25754499

  20. Schema-conformant memories are preferentially consolidated during REM sleep.

    PubMed

    Durrant, Simon J; Cairney, Scott A; McDermott, Cathal; Lewis, Penelope A

    2015-07-01

    Memory consolidation is most commonly described by the standard model, which proposes an initial binding role for the hippocampus which diminishes over time as intracortical connections are strengthened. Recent evidence suggests that slow wave sleep (SWS) plays an essential role in this process. Existing animal and human studies have suggested that memories which fit tightly into an existing knowledge framework or schema might use an alternative consolidation route in which the medial prefrontal cortex takes on the binding role. In this study we sought to investigate the role of sleep in this process using a novel melodic memory task. Participants were asked to remember 32 melodies, half of which conformed to a tonal schema present in all enculturated listeners, and half of which did not fit with this schema. After a 24-h consolidation interval, participants were asked to remember a further 32 melodies, before being given a recognition test in which melodies from both sessions were presented alongside some previously unheard foils. Participants remembered schema-conformant melodies better than non-conformant ones. This was much more strongly the case for consolidated melodies, suggesting that consolidation over a 24-h period preferentially consolidated schema-conformant items. Overnight sleep was monitored between the sessions, and the extent of the consolidation benefit for schema-conformant items was associated with both the amount of REM sleep obtained and EEG theta power in frontal and central regions during REM sleep. Overall our data suggest that REM sleep plays a crucial role in the rapid consolidation of schema-conformant items. This finding is consistent with previous results from animal studies and the SLIMM model of Van Kesteren, Ruiter, Fernández, and Henson (2012), and suggest that REM sleep, rather than SWS, may be involved in an alternative pathway of consolidation for schema-conformant memories.

  1. Increases in cAMP, MAPK Activity and CREB Phosphorylation during REM Sleep: Implications for REM Sleep and Memory Consolidation

    PubMed Central

    Luo, Jie; Phan, Trongha X.; Yang, Yimei; Garelick, Michael G.; Storm, Daniel R.

    2013-01-01

    The cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB) transcriptional pathway is required for consolidation of hippocampus-dependent memory. In mice, this pathway undergoes a circadian oscillation required for memory persistence that reaches a peak during the daytime. Since mice exhibit polyphasic sleep patterns during the day, this suggested the interesting possibility that cAMP, MAPK activity and CREB phosphorylation may be elevated during sleep. Here, we report that cAMP, phospho-p44/42 MAPK and phospho-CREB are higher in rapid eye movement (REM) sleep compared to awake mice but are not elevated in non-rapid eye movement (NREM) sleep. This peak of activity during REM sleep does not occur in mice lacking calmodulin-stimulated adenylyl cyclases, a mouse strain that learns but cannot consolidate hippocampus-dependent memory. We conclude that a preferential increase in cAMP, MAPK activity and CREB phosphorylation during REM sleep may contribute to hippocampus-dependent memory consolidation. PMID:23575844

  2. Hyperkalemic periodic paralysis associated with multiple sleep onset REM periods.

    PubMed

    Iranzo, A; Santamaria, J

    1999-12-15

    A 24-year-old man with sporadic hyperkalemic periodic paralysis (HPP) presented with moderate excessive daytime sleepiness and transitory episodes of weakness which occurred during and after sleep. Multiple sleep latency test (MSLT) demonstrated the presence of five sleep onset REM periods (SOREMPs) and a sleep latency of five minutes. Treatment with a diuretic which decreases serum potassium resolved all the clinical symtomps and a new MSLT showed the absence of SOREMPs and a sleep latency of 13.5 minutes. To our knowledge, the patient herein reported is the first case that associates sleep abnormalities and multiple SOREMPs with HPP. Furthermore, the present case suggests that SOREMPs may be explained by an increased extracellular potassium conductance related to HPP.

  3. Polysomnographic study of nocturnal sleep in idiopathic hypersomnia without long sleep time.

    PubMed

    Pizza, Fabio; Ferri, Raffaele; Poli, Francesca; Vandi, Stefano; Cosentino, Filomena I I; Plazzi, Giuseppe

    2013-04-01

    We investigated nocturnal sleep abnormalities in 19 patients with idiopathic hypersomnia without long sleep time (IH) in comparison with two age- and sex- matched control groups of 13 normal subjects (C) and of 17 patients with narcolepsy with cataplexy (NC), the latter considered as the extreme of excessive daytime sleepiness (EDS). Sleep macro- and micro- (i.e. cyclic alternating pattern, CAP) structure as well as quantitative analysis of EEG, of periodic leg movements during sleep (PLMS), and of muscle tone during REM sleep were compared across groups. IH and NC patients slept more than C subjects, but IH showed the highest levels of sleep fragmentation (e.g. awakenings), associated with a CAP rate higher than NC during lighter sleep stages and lower than C during slow wave sleep respectively, and with the highest relative amount of A3 and the lowest of A1 subtypes. IH showed a delta power in between C and NC groups, whereas muscle tone and PLMS had normal characteristics. A peculiar profile of microstructural sleep abnormalities may contribute to sleep fragmentation and, possibly, EDS in IH.

  4. Evaluating the Evidence Surrounding Pontine Cholinergic Involvement in REM Sleep Generation

    PubMed Central

    Grace, Kevin P.; Horner, Richard L.

    2015-01-01

    Rapid eye movement (REM) sleep – characterized by vivid dreaming, motor paralysis, and heightened neural activity – is one of the fundamental states of the mammalian central nervous system. Initial theories of REM sleep generation posited that induction of the state required activation of the “pontine REM sleep generator” by cholinergic inputs. Here, we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i) the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii) the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii) loss-of-function studies show that endogenous cholinergic input to the PTF is not required for REM sleep generation, and (iv) cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail. PMID:26388832

  5. Evaluating the Evidence Surrounding Pontine Cholinergic Involvement in REM Sleep Generation.

    PubMed

    Grace, Kevin P; Horner, Richard L

    2015-01-01

    Rapid eye movement (REM) sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. Initial theories of REM sleep generation posited that induction of the state required activation of the "pontine REM sleep generator" by cholinergic inputs. Here, we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i) the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii) the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii) loss-of-function studies show that endogenous cholinergic input to the PTF is not required for REM sleep generation, and (iv) cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail. PMID:26388832

  6. Evaluating the Evidence Surrounding Pontine Cholinergic Involvement in REM Sleep Generation.

    PubMed

    Grace, Kevin P; Horner, Richard L

    2015-01-01

    Rapid eye movement (REM) sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. Initial theories of REM sleep generation posited that induction of the state required activation of the "pontine REM sleep generator" by cholinergic inputs. Here, we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i) the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii) the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii) loss-of-function studies show that endogenous cholinergic input to the PTF is not required for REM sleep generation, and (iv) cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail.

  7. A Temporally Controlled Inhibitory Drive Coordinates Twitch Movements during REM Sleep.

    PubMed

    Brooks, Patricia L; Peever, John

    2016-05-01

    During REM sleep, skeletal muscles are paralyzed in one moment but twitch and jerk in the next. REM sleep twitches are traditionally considered random motor events that result from momentary lapses in REM sleep paralysis [1-3]. However, recent evidence indicates that twitches are not byproducts of REM sleep, but are in fact self-generated events that could function to promote motor learning and development [4-6]. If REM twitches are indeed purposefully generated, then they should be controlled by a coordinated and definable mechanism. Here, we used behavioral, electrophysiological, pharmacological, and neuroanatomical methods to demonstrate that an inhibitory drive onto skeletal motoneurons produces a temporally coordinated pattern of muscle twitches during REM sleep. First, we show that muscle twitches in adult rats are not uniformly distributed during REM sleep, but instead follow a well-defined temporal trajectory. They are largely absent during REM initiation but increase steadily thereafter, peaking toward REM termination. Next, we identify the transmitter mechanism that controls the temporal nature of twitch activity. Specifically, we show that a GABA and glycine drive onto motoneurons prevents twitch activity during REM initiation, but progressive weakening of this drive functions to promote twitch activity during REM termination. These results demonstrate that REM twitches are not random byproducts of REM sleep, but are instead rather coherently generated events controlled by a temporally variable inhibitory drive. PMID:27040781

  8. A Temporally Controlled Inhibitory Drive Coordinates Twitch Movements during REM Sleep.

    PubMed

    Brooks, Patricia L; Peever, John

    2016-05-01

    During REM sleep, skeletal muscles are paralyzed in one moment but twitch and jerk in the next. REM sleep twitches are traditionally considered random motor events that result from momentary lapses in REM sleep paralysis [1-3]. However, recent evidence indicates that twitches are not byproducts of REM sleep, but are in fact self-generated events that could function to promote motor learning and development [4-6]. If REM twitches are indeed purposefully generated, then they should be controlled by a coordinated and definable mechanism. Here, we used behavioral, electrophysiological, pharmacological, and neuroanatomical methods to demonstrate that an inhibitory drive onto skeletal motoneurons produces a temporally coordinated pattern of muscle twitches during REM sleep. First, we show that muscle twitches in adult rats are not uniformly distributed during REM sleep, but instead follow a well-defined temporal trajectory. They are largely absent during REM initiation but increase steadily thereafter, peaking toward REM termination. Next, we identify the transmitter mechanism that controls the temporal nature of twitch activity. Specifically, we show that a GABA and glycine drive onto motoneurons prevents twitch activity during REM initiation, but progressive weakening of this drive functions to promote twitch activity during REM termination. These results demonstrate that REM twitches are not random byproducts of REM sleep, but are instead rather coherently generated events controlled by a temporally variable inhibitory drive.

  9. Sleep disturbances in Parkinson's disease: the contribution of dopamine in REM sleep regulation.

    PubMed

    Lima, Marcelo M S

    2013-10-01

    Nearly all patients with Parkinson's disease (PD) have sleep disturbances. While it has been suggested that these disturbances involve a dopaminergic component, the specific mechanisms that contribute to this behavior are far from being fully understood. In this article, we have reviewed the current understanding of the linkage between sleep and PD, focusing on the participation of the dopaminergic system in the regulation of rapid eye movement (REM) sleep. The presence of an REM sleep behavior disorder in patients with PD might reflect the early involvement of dopaminergic neurotransmission in REM sleep-related structures. Therefore, it has been suggested that these structures are affected by an imbalance of dopamine levels. Several studies have demonstrated that neurons in the substantia nigra pars compacta (SNpc) and in the ventral tegmental area (VTA) are active during REM sleep and that sleep-related disturbances may result when these neurons are targeted by neurotoxins. We discuss current evidence suggesting the presence of a putative reciprocal connectivity between the SNpc, VTA, the pedunculopontine tegmental nucleus and reticular formation, which may exert an important influence on the REM sleep mechanism. This review provides a comprehensive overview of the literature that addresses this challenging and unrecognized component of PD.

  10. Estradiol suppresses recovery of REM sleep following sleep deprivation in ovariectomized female rats.

    PubMed

    Schwartz, Michael D; Mong, Jessica A

    2011-10-24

    Sleep complaints such as insufficient sleep and insomnia are twice as prevalent in women. Symptoms of sleep disruption are often coincident with changes in the gonadal hormone profile across a women's lifespan. Data from a number of different species, including humans, non-human primates and rodents strongly implicate a role for gonadal hormones in the modulation of sleep. In female rats, increased levels of circulating estradiol increase wakefulness and reduce sleep in the dark phase. In this study, we asked whether this reduction in sleep is driven by estradiol-dependent reduction in sleep need during the dark phase by assessing sleep before and after sleep deprivation (SD). Ovariectomized rats implanted with EEG telemetry transmitters were given Silastic capsules containing either 17-β estradiol in sesame oil (E2) or sesame oil alone. After a 24-hour baseline, animals were sleep-deprived via gentle handling for the entire 12-hour light phase, and then allowed to recover. E2 treatment suppressed baseline REM sleep duration in the dark phase, but not NREM or Wake duration, within three days. While SD induced a compensatory increase in REM duration in both groups, this increase was smaller in E2-treated rats compared to oils, as measured in absolute duration as well as by relative increase over baseline. Thus, E2 suppressed REM sleep in the dark phase both before and after SD. E2 also suppressed NREM and increased waking in the early- to mid-dark phase on the day after SD. NREM delta power tracked NREM sleep before and after SD, with small hormone-dependent reductions in delta power in recovery, but not spontaneous sleep. These results demonstrate that E2 powerfully and specifically suppresses spontaneous and recovery REM sleep in the dark phase, and suggest that ovarian steroids may consolidate circadian sleep-wake rhythms.

  11. Effects of selective REM sleep deprivation on prefrontal gamma activity and executive functions.

    PubMed

    Corsi-Cabrera, M; Rosales-Lagarde, A; del Río-Portilla, Y; Sifuentes-Ortega, R; Alcántara-Quintero, B

    2015-05-01

    Given that the dorsolateral prefrontal cortex is involved in executive functions and is deactivated and decoupled from posterior associative regions during REM sleep, that Gamma temporal coupling involved in information processing is enhanced during REM sleep, and that adult humans spend about 90 min of every 24h in REM sleep, it might be expected that REM sleep deprivation would modify Gamma temporal coupling and have a deteriorating effect on executive functions. We analyzed EEG Gamma activity and temporal coupling during implementation of a rule-guided task before and after REM sleep deprivation and its effect on verbal fluency, flexible thinking and selective attention. After two nights in the laboratory for adaptation, on the third night subjects (n=18) were randomly assigned to either selective REM sleep deprivation effectuated by awakening them at each REM sleep onset or, the same number of NREM sleep awakenings as a control for unspecific effects of sleep interruptions. Implementation of abstract rules to guide behavior required greater activation and synchronization of Gamma activity in the frontopolar regions after REM sleep reduction from 20.6% at baseline to just 3.93% of total sleep time. However, contrary to our hypothesis, both groups showed an overall improvement in executive task performance and no effect on their capacity to sustain selective attention. These results suggest that after one night of selective REM sleep deprivation executive functions can be compensated by increasing frontal activation and they still require the participation of supervisory control by frontopolar regions.

  12. Management of REM sleep behavior disorder: An evidence based review

    PubMed Central

    Devnani, Preeti; Fernandes, Racheal

    2015-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment behavior resulting from a loss of REM skeletal muscle atonia. The neurobiology of REM sleep and the characteristic features of REM atonia have an important basis for understanding the aggravating etiologies the proposed pharmacological interventions in its management. This review outlines the evidence for behavioral and therapeutic measures along with evidence-based guidelines for their implementation, impact on falls, and effect on polysomnography (PSG) while highlighting the non-motor, autonomic, and cognitive impact of this entity. PubMed databases were reviewed upto May 2013 in peer-reviewed scientific literature regarding the pathophysiology and management of RBD in adults. The literature was graded according to the Oxford centre of evidence-based Medicine Levels. An early intervention that helps prevent consequences such as falls and provides a base for intervention with neuroprotective mechanisms and allocates a unique platform that RBD portrays with its high risk of disease conversion with a sufficiently long latency. RBD provides a unique platform with its high risk of disease conversion with a sufficiently long latency, providing an opportunity for early intervention both to prevent consequences such as falls and provide a base for intervention with neuroprotective mechanisms. PMID:25745301

  13. Association between the activation of MCH and orexin immunorective neurons and REM sleep architecture during REM rebound after a three day long REM deprivation.

    PubMed

    Kitka, Tamas; Adori, Csaba; Katai, Zita; Vas, Szilvia; Molnar, Eszter; Papp, Rege S; Toth, Zsuzsanna E; Bagdy, Gyorgy

    2011-10-01

    Rapid eye movement (REM) sleep rebound following REM deprivation using the platform-on-water method is characterized by increased time spent in REM sleep and activation of melanin-concentrating hormone (MCH) expressing neurons. Orexinergic neurons discharge reciprocally to MCH-ergic neurons across the sleep-wake cycle. However, the relation between REM architecture and the aforementioned neuropeptides remained unclear. MCH-ergic neurons can be divided into two subpopulations regarding their cocaine- and amphetamine-regulated transcript (CART) immunoreactivity, and among them the activation of CART-immunoreactive subpopulation is higher during the REM rebound. However, the possible role of stress in this association has not been elucidated. Our aims were to analyze the relationship between the architecture of REM rebound and the activation of hypothalamic MCH-ergic and orexinergic neurons. We also intended to separate the effect of stress and REM deprivation on the subsequent activation of subpopulations of MCH-ergic neurons. In order to detect neuronal activity, we performed MCH/cFos and orexin/cFos double immunohistochemistry on home cage, sleep deprived and sleep-rebound rats using the platform-on-water method with small and large (stress control) platforms. Furthermore, REM architecture was analyzed and a triple MCH/CART/cFos immunohistochemistry was also performed on the rebound groups in the same animals. We found that the activity of MCH- and orexin-immunoreactive neurons during REM rebound was positively and negatively correlated with the number of REM bouts, respectively. A negative reciprocal correlation was also found between the activation of MCH- and orexin-immunoreactive neurons during REM rebound. Furthermore, difference between the activation of CART-immunoreactive (CART-IR) and non-CART-immunoreactive MCH-ergic neuron subpopulations was found only after selective REM deprivation, it was absent in the large platform (stress control) rebound group

  14. Maternal stress induces adult reduced REM sleep and melatonin level.

    PubMed

    Feng, Pingfu; Hu, Yufen; Vurbic, Drina; Guo, Yang

    2012-05-01

    We have previously reported that neonatal maternal deprivation (MD) resulted in a decrease of total sleep and an increase of orexin A in adult rats. Now, we characterized features of sleep, activity, and melatonin levels in rats neonatally treated with MD and control (MC) procedures. Adult male Sprague-Dawley rats were treated with either MD or MC procedures for 10 days starting at postnatal day 4. At 3 months of age, sleep was recorded for 48 h in one set of MD and MC rats, while another set of MD and MC rats was measured for locomotor activity (under LD = 12:12). Melatonin levels in the blood, pineal gland, and hypothalamus were measured as well as clock protein level in the hypothalamus. Compared to the MC rats, REM sleep in the MD rats was significantly reduced in the light periods but not in the dark periods. Both quiet wake and total wake in the MD rats were significantly increased during the light period compared to the MC rats. The weight of the pineal gland of the MD rats was significantly smaller than in MC rats. Melatonin levels of the MD group were significantly reduced in the pineal gland and hypothalamus compared to the MC group. No significant difference was identified between groups in the expression of the clock protein in the hypothalamus. Neonatal MD resulted in reduced REM sleep and melatonin levels, without changes of circadian cycle of locomotor activity and levels of clock protein.

  15. Selective REM-sleep deprivation does not diminish emotional memory consolidation in young healthy subjects.

    PubMed

    Morgenthaler, Jarste; Wiesner, Christian D; Hinze, Karoline; Abels, Lena C; Prehn-Kristensen, Alexander; Göder, Robert

    2014-01-01

    Sleep enhances memory consolidation and it has been hypothesized that rapid eye movement (REM) sleep in particular facilitates the consolidation of emotional memory. The aim of this study was to investigate this hypothesis using selective REM-sleep deprivation. We used a recognition memory task in which participants were shown negative and neutral pictures. Participants (N=29 healthy medical students) were separated into two groups (undisturbed sleep and selective REM-sleep deprived). Both groups also worked on the memory task in a wake condition. Recognition accuracy was significantly better for negative than for neutral stimuli and better after the sleep than the wake condition. There was, however, no difference in the recognition accuracy (neutral and emotional) between the groups. In summary, our data suggest that REM-sleep deprivation was successful and that the resulting reduction of REM-sleep had no influence on memory consolidation whatsoever. PMID:24587073

  16. Selective REM-sleep deprivation does not diminish emotional memory consolidation in young healthy subjects.

    PubMed

    Morgenthaler, Jarste; Wiesner, Christian D; Hinze, Karoline; Abels, Lena C; Prehn-Kristensen, Alexander; Göder, Robert

    2014-01-01

    Sleep enhances memory consolidation and it has been hypothesized that rapid eye movement (REM) sleep in particular facilitates the consolidation of emotional memory. The aim of this study was to investigate this hypothesis using selective REM-sleep deprivation. We used a recognition memory task in which participants were shown negative and neutral pictures. Participants (N=29 healthy medical students) were separated into two groups (undisturbed sleep and selective REM-sleep deprived). Both groups also worked on the memory task in a wake condition. Recognition accuracy was significantly better for negative than for neutral stimuli and better after the sleep than the wake condition. There was, however, no difference in the recognition accuracy (neutral and emotional) between the groups. In summary, our data suggest that REM-sleep deprivation was successful and that the resulting reduction of REM-sleep had no influence on memory consolidation whatsoever.

  17. Blockage of dopaminergic D(2) receptors produces decrease of REM but not of slow wave sleep in rats after REM sleep deprivation.

    PubMed

    Lima, Marcelo M S; Andersen, Monica L; Reksidler, Angela B; Silva, Andressa; Zager, Adriano; Zanata, Sílvio M; Vital, Maria A B F; Tufik, Sergio

    2008-04-01

    Dopamine (DA) has, as of late, become singled out from the profusion of other neurotransmitters as what could be called a key substance, in the regulation of the sleep-wake states. We have hypothesized that dopaminergic D(2) receptor blockage induced by haloperidol could generate a reduction or even an ablation of rapid eye movement (REM) sleep. Otherwise, the use of the selective D(2) agonist, piribedil, could potentiate REM sleep. Electrophysiological findings demonstrate that D(2) blockage produced a dramatic reduction of REM sleep during the rebound (REB) period after 96 h of REM sleep deprivation (RSD). This reduction of REM sleep was accompanied by an increment in SWS, which is possibly accounted for the observed increase in the sleep efficiency. Conversely, our findings also demonstrate that the administration of piribedil did not generate additional increase of REM sleep. Additionally, D(2) receptors were found down-regulated, in the haloperidol group, after RSD, and subsequently up-regulated after REB group, contrasting to the D(1) down-regulation at the same period. In this sense, the current data indicate a participation of the D(2) receptor for REM sleep regulation and consequently in the REM sleep/SWS balance. Herein, we propose that the mechanism underlying the striatal D(2) up-regulation is due to an effect as consequence of RSD which originally produces selective D(2) supersensitivity, and after its period probably generates a surge in D(2) expression. In conclusion we report a particular action of the dopaminergic neurotransmission in REM sleep relying on D(2) activation.

  18. Arousal state feedback as a potential physiological generator of the ultradian REM/NREM sleep cycle.

    PubMed

    Phillips, A J K; Robinson, P A; Klerman, E B

    2013-02-21

    Human sleep episodes are characterized by an approximately 90-min ultradian oscillation between rapid eye movement (REM) and non-REM (NREM) sleep stages. The source of this oscillation is not known. Pacemaker mechanisms for this rhythm have been proposed, such as a reciprocal interaction network, but these fail to account for documented homeostatic regulation of both sleep stages. Here, two candidate mechanisms are investigated using a simple model that has stable states corresponding to Wake, REM sleep, and NREM sleep. Unlike other models of the ultradian rhythm, this model of sleep dynamics does not include an ultradian pacemaker, nor does it invoke a hypothetical homeostatic process that exists purely to drive ultradian rhythms. Instead, only two inputs are included: the homeostatic drive for Sleep and the circadian drive for Wake. These two inputs have been the basis for the most influential Sleep/Wake models, but have not previously been identified as possible ultradian rhythm generators. Using the model, realistic ultradian rhythms are generated by arousal state feedback to either the homeostatic or circadian drive. For the proposed 'homeostatic mechanism', homeostatic pressure increases in Wake and REM sleep, and decreases in NREM sleep. For the proposed 'circadian mechanism', the circadian drive is up-regulated in Wake and REM sleep, and is down-regulated in NREM sleep. The two mechanisms are complementary in the features they capture. The homeostatic mechanism reproduces experimentally observed rebounds in NREM sleep duration and intensity following total sleep deprivation, and rebounds in both NREM sleep intensity and REM sleep duration following selective REM sleep deprivation. The circadian mechanism does not reproduce sleep state rebounds, but more accurately reproduces the temporal patterns observed in a normal night of sleep. These findings have important implications in terms of sleep physiology and they provide a parsimonious explanation for the

  19. Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation.

    PubMed

    Boyce, Richard; Glasgow, Stephen D; Williams, Sylvain; Adamantidis, Antoine

    2016-05-13

    Rapid eye movement sleep (REMS) has been linked with spatial and emotional memory consolidation. However, establishing direct causality between neural activity during REMS and memory consolidation has proven difficult because of the transient nature of REMS and significant caveats associated with REMS deprivation techniques. In mice, we optogenetically silenced medial septum γ-aminobutyric acid-releasing (MS(GABA)) neurons, allowing for temporally precise attenuation of the memory-associated theta rhythm during REMS without disturbing sleeping behavior. REMS-specific optogenetic silencing of MS(GABA) neurons selectively during a REMS critical window after learning erased subsequent novel object place recognition and impaired fear-conditioned contextual memory. Silencing MS(GABA) neurons for similar durations outside REMS episodes had no effect on memory. These results demonstrate that MS(GABA) neuronal activity specifically during REMS is required for normal memory consolidation. PMID:27174984

  20. Effects of biperiden on sleep at baseline and after 72 h of REM sleep deprivation in the cat.

    PubMed

    Salin-Pascual, R J; Jimenez-Anguiano, A; Granados-Fuentes, D; Drucker-Colin, R

    1992-01-01

    We examined the effects of the muscarinic M1 antagonist biperiden in cats. In the first experiment a dose-response analysis was performed with intraventricular injection (IV ventricle) of biperiden. In the second experiment after REM sleep deprivation cats were injected with either biperiden (0.1 mg/kg) or saline. Biperiden produced a reduction in REM sleep percentage and an increase in REM sleep latency with these high doses. The 0.1 mg/kg biperiden dose, which did not suppress REM sleep at baseline, did reduce the REM sleep rebound. The present study suggests a modulatory role of biperiden on REM sleep regulatory processes. The fact that an effect of biperiden is noted only at the high doses suggests that at these doses the drug is influencing non-M1 receptors. Changes in the sensitivity of these receptors as a result of REM sleep deprivation might explain why a dose of biperiden will reduce REM sleep rebound, while being ineffective in suppressing REM sleep at baseline.

  1. Increased Reward-Related Behaviors during Sleep and Wakefulness in Sleepwalking and Idiopathic Nightmares

    PubMed Central

    Perogamvros, Lampros; Aberg, Kristoffer; Gex-Fabry, Marianne; Perrig, Stephen; Cloninger, C. Robert; Schwartz, Sophie

    2015-01-01

    Background We previously suggested that abnormal sleep behaviors, i.e., as found in parasomnias, may often be the expression of increased activity of the reward system during sleep. Because nightmares and sleepwalking predominate during REM and NREM sleep respectively, we tested here whether exploratory excitability, a waking personality trait reflecting high activity within the mesolimbic dopaminergic (ML-DA) system, may be associated with specific changes in REM and NREM sleep patterns in these two sleep disorders. Methods Twenty-four unmedicated patients with parasomnia (12 with chronic sleepwalking and 12 with idiopathic nightmares) and no psychiatric comorbidities were studied. Each patient spent one night of sleep monitored by polysomnography. The Temperament and Character Inventory (TCI) was administered to all patients and healthy controls from the Geneva population (n = 293). Results Sleepwalkers were more anxious than patients with idiopathic nightmares (Spielberger Trait anxiety/STAI-T), but the patient groups did not differ on any personality dimension as estimated by the TCI. Compared to controls, parasomnia patients (sleepwalkers together with patients with idiopathic nightmares) scored higher on the Novelty Seeking (NS) TCI scale and in particular on the exploratory excitability/curiosity (NS1) subscale, and lower on the Self-directedness (SD) TCI scale, suggesting a general increase in reward sensitivity and impulsivity. Furthermore, parasomnia patients tended to worry about social separation persistently, as indicated by greater anticipatory worry (HA1) and dependence on social attachment (RD3). Moreover, exploratory excitability (NS1) correlated positively with the severity of parasomnia (i.e., the frequency of self-reported occurrences of nightmares and sleepwalking), and with time spent in REM sleep in patients with nightmares. Conclusions These results suggest that patients with parasomnia might share common waking personality traits associated

  2. Identification of the transmitter and receptor mechanisms responsible for REM sleep paralysis.

    PubMed

    Brooks, Patricia L; Peever, John H

    2012-07-18

    During REM sleep the CNS is intensely active, but the skeletal motor system is paradoxically forced into a state of muscle paralysis. The mechanisms that trigger REM sleep paralysis are a matter of intense debate. Two competing theories argue that it is caused by either active inhibition or reduced excitation of somatic motoneuron activity. Here, we identify the transmitter and receptor mechanisms that function to silence skeletal muscles during REM sleep. We used behavioral, electrophysiological, receptor pharmacology and neuroanatomical approaches to determine how trigeminal motoneurons and masseter muscles are switched off during REM sleep in rats. We show that a powerful GABA and glycine drive triggers REM paralysis by switching off motoneuron activity. This drive inhibits motoneurons by targeting both metabotropic GABA(B) and ionotropic GABA(A)/glycine receptors. REM paralysis is only reversed when motoneurons are cut off from GABA(B), GABA(A) and glycine receptor-mediated inhibition. Neither metabotropic nor ionotropic receptor mechanisms alone are sufficient for generating REM paralysis. These results demonstrate that multiple receptor mechanisms trigger REM sleep paralysis. Breakdown in normal REM inhibition may underlie common sleep motor pathologies such as REM sleep behavior disorder.

  3. Identification of the transmitter and receptor mechanisms responsible for REM sleep paralysis.

    PubMed

    Brooks, Patricia L; Peever, John H

    2012-07-18

    During REM sleep the CNS is intensely active, but the skeletal motor system is paradoxically forced into a state of muscle paralysis. The mechanisms that trigger REM sleep paralysis are a matter of intense debate. Two competing theories argue that it is caused by either active inhibition or reduced excitation of somatic motoneuron activity. Here, we identify the transmitter and receptor mechanisms that function to silence skeletal muscles during REM sleep. We used behavioral, electrophysiological, receptor pharmacology and neuroanatomical approaches to determine how trigeminal motoneurons and masseter muscles are switched off during REM sleep in rats. We show that a powerful GABA and glycine drive triggers REM paralysis by switching off motoneuron activity. This drive inhibits motoneurons by targeting both metabotropic GABA(B) and ionotropic GABA(A)/glycine receptors. REM paralysis is only reversed when motoneurons are cut off from GABA(B), GABA(A) and glycine receptor-mediated inhibition. Neither metabotropic nor ionotropic receptor mechanisms alone are sufficient for generating REM paralysis. These results demonstrate that multiple receptor mechanisms trigger REM sleep paralysis. Breakdown in normal REM inhibition may underlie common sleep motor pathologies such as REM sleep behavior disorder. PMID:22815493

  4. Antidepressant suppression of non-REM sleep spindles and REM sleep impairs hippocampus-dependent learning while augmenting striatum-dependent learning.

    PubMed

    Watts, Alain; Gritton, Howard J; Sweigart, Jamie; Poe, Gina R

    2012-09-26

    Rapid eye movement (REM) sleep enhances hippocampus-dependent associative memory, but REM deprivation has little impact on striatum-dependent procedural learning. Antidepressant medications are known to inhibit REM sleep, but it is not well understood if antidepressant treatments impact learning and memory. We explored antidepressant REM suppression effects on learning by training animals daily on a spatial task under familiar and novel conditions, followed by training on a procedural memory task. Daily treatment with the antidepressant and norepinephrine reuptake inhibitor desipramine (DMI) strongly suppressed REM sleep in rats for several hours, as has been described in humans. We also found that DMI treatment reduced the spindle-rich transition-to-REM sleep state (TR), which has not been previously reported. DMI REM suppression gradually weakened performance on a once familiar hippocampus-dependent maze (reconsolidation error). DMI also impaired learning of the novel maze (consolidation error). Unexpectedly, learning of novel reward positions and memory of familiar positions were equally and oppositely correlated with amounts of TR sleep. Conversely, DMI treatment enhanced performance on a separate striatum-dependent, procedural T-maze task that was positively correlated with the amounts of slow-wave sleep (SWS). Our results suggest that learning strategy switches in patients taking REM sleep-suppressing antidepressants might serve to offset sleep-dependent hippocampal impairments to partially preserve performance. State-performance correlations support a model wherein reconsolidation of hippocampus-dependent familiar memories occurs during REM sleep, novel information is incorporated and consolidated during TR, and dorsal striatum-dependent procedural learning is augmented during SWS.

  5. Repeated REM sleep deprivation after chronic haloperidol administration in the rat.

    PubMed

    Salín-Pascual, R J; García-Ferreiro, R; Moro-López, M L; Blanco-Centurión, C; Drucker-Colín, R

    1997-06-01

    Repeated haloperidol administration produces up-regulation of dopamine (DA) receptors. REM sleep deprivation (REMSD) does also, but in addition, has been shown to produce REM sleep rebound. Should DA receptor up-regulation play a role in REM sleep rebound, haloperidol could conceivably have effects similar to those observed following REMSD. This is the central question investigated in this study. Male Wistar rats were prepared for sleep recordings. They were randomly assigned to the following groups: group 1, REMSD by small platforms (40 h REMSD + 8 h recording); group 2, was the large platform control group (40 h in large platforms + 8 h of recording); group 3, received 2-week daily administration of haloperidol (3 mg/kg, i.p.) plus REMSD (40 h REMSD + 8 h of recording); group 4, 2-week administration of haloperidol (3 mg/kg) without sleep manipulation and at the end 40 h were allowed to elapse, following which 8 h of sleep recordings was carried out. In each group the sleep manipulation and/or sleep recordings were repeated five consecutive times. Repeated REMSD produced increases of REM sleep time after each recovery in group 1. Large platforms did not produce increases of REM sleep during the recovery trials. The 2-week administration of haloperidol plus REMSD prevented REM sleep rebound (group 3). The 2-week administration of haloperidol without sleep manipulation (group 4) produced a REM sleep reduction. Dopamine modulation seems not to be important for REM sleep rebound. Hypersensitivity of DA receptors developed after REMSD may be an epiphenomenon associated with this sleep manipulation, but seems not to participate in REM sleep enhancement after REMSD.

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

    PubMed

    Shiromani, P J; Armstrong, D M; Bruce, G; Hersh, L B; Groves, P M; Gillin, J C

    1987-03-01

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

  7. Rapid increase to double breathing rate appears during REM sleep in synchrony with REM - a higher CNS control of breathing? -.

    PubMed

    Sato, Shinichi; Kanbayashi, Takashi; Kondo, Hideaki; Matsubuchi, Namiko; Ono, Kyoichi; Shimizu, Tetsuo

    2010-01-01

    Breathing rate (BR) during rapid eye movement (REM) sleep is known to fluctuate largely, while increases in BR during REM sleep reported were small. In our mice experiments, we found that mice exhibit a rapid increase in instantaneous BR (RIBR) of >2 fold during natural sleep with accompanying atonia, laying their sides down. The RIBR was further found in a sleeping mouse attached with EEG electrodes when the EEG amplitude and delta wave power were lower. Therefore, it is likely that mice show RIBRs during REM sleep. Interestingly, similar RIBRs accompanied by atonia and REM burst during REM sleep were also found in humans by standard polysomnographic studies in 11 healthy volunteers (age: 22.3 +/- 2.8) with BR measurement by nasal/oral airflow sensors and chest/abdomen belt sensors. All subjects underwent RIBR of doubled BR at least once a night. As SpO(2) before RIBRs was a level not effective to be a respiratory stimulant (96.7 +/- 1.6 %, n = 63), the RIBR seems to be controlled by higher central nervous system rather than autonomic nervous system control on response to central and peripheral chemical sensors. In fact, tachypnea with suppressed amplitude during RIBR resulted in a slight fall in SpO(2) (96.4 +/- 1.7 %, p = 0.0007). In the present study, RIBRs accompanied by atonia and REM were not necessarily consistent in change in rate and/or amplitude, therefore, these various pattern of RIBRs may be potential indices of dreams with various emotional contents. Analysis of instantaneous BR, thus, may be a helpful tool for understanding the neural control of breathing during REM sleep. PMID:20217359

  8. The effect of a REM sleep deprivation procedure on different aspects of memory function in humans.

    PubMed

    Saxvig, Ingvild West; Lundervold, Astri Johansen; Grønli, Janne; Ursin, Reidun; Bjorvatn, Bjørn; Portas, Chiara Maria

    2008-03-01

    Previous studies have suggested that memory is dependent on the occurrence of REM sleep. Research has mainly focused on two distinct types of memory function, declarative and procedural, and it seems that the latter may more directly depend on REM sleep. Memory consolidation has been more investigated than acquisition, maintenance, and recall, despite the fact that sleep may affect flow of information into/from storage. Moreover, tests have often been limited to stimuli within only one modality (usually visual or verbal). This study aimed to clarify the role of REM sleep in memory by investigating aspects of memory function, processing, and modality in the same experimental setting. Tests of acquisition and consolidation of multiple aspects of memory function within the visual and verbal modalities were administrated to subjects before and after REM sleep deprivation. Results show that test performance was not affected by REM sleep deprivation.

  9. REM sleep deprivation inhibits LTP in vivo in area CA1 of rat hippocampus.

    PubMed

    Kim, Eun Young; Mahmoud, Ghada S; Grover, Lawrence M

    2005-11-18

    Rapid eye movement (REM) sleep deprivation has previously been shown to interfere with normal learning and memory and to inhibit long-term potentiation (LTP) in vitro. Previous studies on REM sleep deprivation and LTP have relied on in vitro analysis in isolated brain slices taken from animals following several days of sleep deprivation. LTP in the hippocampus in situ may differ from LTP in vitro due to modulatory inputs from other brain regions, which are altered after REM sleep deprivation. Here, we examined LTP in unanesthetized, behaving animals on the first and second recovery days following REM sleep deprivation to determine if similar effects are seen in vivo as previously reported in vitro. We found that LTP was significantly impaired in REM sleep-deprived animals on the second recovery day but not the first recovery day. Our results extend previous findings by showing that REM sleep deprivation continues to affect hippocampal function for more than 24h following the end of deprivation. Our results also suggest the presence of a modulatory process not present in vitro. Our findings are not explained by stress during REM sleep deprivation because equivalent circulating corticosterone levels (an index of stress) were found during both REM sleep deprivation and control treatment.

  10. Sleep-Related Declarative Memory Consolidation and Verbal Replay during Sleep Talking in Patients with REM Sleep Behavior Disorder

    PubMed Central

    Uguccioni, Ginevra; Pallanca, Olivier; Golmard, Jean-Louis; Dodet, Pauline; Herlin, Bastien; Leu-Semenescu, Smaranda; Arnulf, Isabelle

    2013-01-01

    Objective To determine if sleep talkers with REM sleep behavior disorder (RBD) would utter during REM sleep sentences learned before sleep, and to evaluate their verbal memory consolidation during sleep. Methods Eighteen patients with RBD and 10 controls performed two verbal memory tasks (16 words from the Free and Cued Selective Reminding Test and a 220-263 word long modified Story Recall Test) in the evening, followed by nocturnal video-polysomnography and morning recall (night-time consolidation). In 9 patients with RBD, daytime consolidation (morning learning/recall, evening recall) was also evaluated with the modified Story Recall Test in a cross-over order. Two RBD patients with dementia were studied separately. Sleep talking was recorded using video-polysomnography, and the utterances were compared to the studied texts by two external judges. Results Sleep-related verbal memory consolidation was maintained in patients with RBD (+24±36% words) as in controls (+9±18%, p=0.3). The two demented patients with RBD also exhibited excellent nighttime consolidation. The post-sleep performance was unrelated to the sleep measures (including continuity, stages, fragmentation and apnea-hypopnea index). Daytime consolidation (-9±19%) was worse than night-time consolidation (+29±45%, p=0.03) in the subgroup of 9 patients with RBD. Eleven patients with RBD spoke during REM sleep and pronounced a median of 20 words, which represented 0.0003% of sleep with spoken language. A single patient uttered a sentence that was judged to be semantically (but not literally) related to the text learned before sleep. Conclusion Verbal declarative memory normally consolidates during sleep in patients with RBD. The incorporation of learned material within REM sleep-associated sleep talking in one patient (unbeknownst to himself) at the semantic level suggests a replay at a highly cognitive creative level. PMID:24349492

  11. Orexin-1 receptor blockade dysregulates REM sleep in the presence of orexin-2 receptor antagonism

    PubMed Central

    Dugovic, Christine; Shelton, Jonathan E.; Yun, Sujin; Bonaventure, Pascal; Shireman, Brock T.; Lovenberg, Timothy W.

    2014-01-01

    In accordance with the prominent role of orexins in the maintenance of wakefulness via activation of orexin-1 (OX1R) and orexin-2 (OX2R) receptors, various dual OX1/2R antagonists have been shown to promote sleep in animals and humans. While selective blockade of OX2R seems to be sufficient to initiate and prolong sleep, the beneficial effect of additional inhibition of OX1R remains controversial. The relative contribution of OX1R and OX2R to the sleep effects induced by a dual OX1/2R antagonist was further investigated in the rat, and specifically on rapid eye movement (REM) sleep since a deficiency of the orexin system is associated with narcolepsy/cataplexy based on clinical and pre-clinical data. As expected, the dual OX1/2R antagonist SB-649868 was effective in promoting non-REM (NREM) and REM sleep following oral dosing (10 and 30 mg/kg) at the onset of the dark phase. However, a disruption of REM sleep was evidenced by a more pronounced reduction in the onset of REM as compared to NREM sleep, a marked enhancement of the REM/total sleep ratio, and the occurrence of a few episodes of direct wake to REM sleep transitions (REM intrusion). When administered subcutaneously, the OX2R antagonist JNJ-10397049 (10 mg/kg) increased NREM duration whereas the OX1R antagonist GSK-1059865 (10 mg/kg) did not alter sleep. REM sleep was not affected either by OX2R or OX1R blockade alone, but administration of the OX1R antagonist in combination with the OX2R antagonist induced a significant reduction in REM sleep latency and an increase in REM sleep duration at the expense of the time spent in NREM sleep. These results indicate that additional blockade of OX1R to OX2R antagonism elicits a dysregulation of REM sleep by shifting the balance in favor of REM sleep at the expense of NREM sleep that may increase the risk of adverse events. Translation of this hypothesis remains to be tested in the clinic. PMID:24592208

  12. Phasic Motor Activity of Respiratory and Non-Respiratory Muscles in REM Sleep

    PubMed Central

    Fraigne, Jimmy J.; Orem, John M.

    2011-01-01

    Objectives: In this study, we quantified the profiles of phasic activity in respiratory muscles (diaphragm, genioglossus and external intercostal) and non-respiratory muscles (neck and extensor digitorum) across REM sleep. We hypothesized that if there is a unique pontine structure that controls all REM sleep phasic events, the profiles of the phasic twitches of different muscle groups should be identical. Furthermore, we described how respiratory parameters (e.g., frequency, amplitude, and effort) vary across REM sleep to determine if phasic processes affect breathing. Methods: Electrodes were implanted in Wistar rats to record brain activity and muscle activity of neck, extensor digitorum, diaphragm, external intercostal, and genioglossal muscles. Ten rats were studied to obtain 313 REM periods over 73 recording days. Data were analyzed offline and REM sleep activity profiles were built for each muscle. In 6 animals, respiratory frequency, effort, amplitude, and inspiratory peak were also analyzed during 192 REM sleep periods. Results: Respiratory muscle phasic activity increased in the second part of the REM period. For example, genioglossal activity increased in the second part of the REM period by 63.8% compared to the average level during NREM sleep. This profile was consistent between animals and REM periods (η2 = 0.58). This increased activity seen in respiratory muscles appeared as irregular bursts and trains of activity that could affect rythmo-genesis. Indeed, the increased integrated activity seen in the second part of the REM period in the diaphragm was associated with an increase in the number (28.3%) and amplitude (30%) of breaths. Non-respiratory muscle phasic activity in REM sleep did not have a profile like the phasic activity of respiratory muscles. Time in REM sleep did not have an effect on nuchal activity (P = 0.59). Conclusion: We conclude that the concept of a common pontine center controlling all REM phasic events is not supported by our

  13. The supramammillary nucleus and the claustrum activate the cortex during REM sleep

    PubMed Central

    Renouard, Leslie; Billwiller, Francesca; Ogawa, Keiko; Clément, Olivier; Camargo, Nutabi; Abdelkarim, Mouaadh; Gay, Nadine; Scoté-Blachon, Céline; Touré, Rouguy; Libourel, Paul-Antoine; Ravassard, Pascal; Salvert, Denise; Peyron, Christelle; Claustrat, Bruno; Léger, Lucienne; Salin, Paul; Malleret, Gael; Fort, Patrice; Luppi, Pierre-Hervé

    2015-01-01

    Evidence in humans suggests that limbic cortices are more active during rapid eye movement (REM or paradoxical) sleep than during waking, a phenomenon fitting with the presence of vivid dreaming during this state. In that context, it seemed essential to determine which populations of cortical neurons are activated during REM sleep. Our aim in the present study is to fill this gap by combining gene expression analysis, functional neuroanatomy, and neurochemical lesions in rats. We find in rats that, during REM sleep hypersomnia compared to control and REM sleep deprivation, the dentate gyrus, claustrum, cortical amygdaloid nucleus, and medial entorhinal and retrosplenial cortices are the only cortical structures containing neurons with an increased expression of Bdnf, FOS, and ARC, known markers of activation and/or synaptic plasticity. Further, the dentate gyrus is the only cortical structure containing more FOS-labeled neurons during REM sleep hypersomnia than during waking. Combining FOS staining, retrograde labeling, and neurochemical lesion, we then provide evidence that FOS overexpression occurring in the cortex during REM sleep hypersomnia is due to projections from the supramammillary nucleus and the claustrum. Our results strongly suggest that only a subset of cortical and hippocampal neurons are activated and display plasticity during REM sleep by means of ascending projections from the claustrum and the supramammillary nucleus. Our results pave the way for future studies to identify the function of REM sleep with regard to dreaming and emotional memory processing. PMID:26601158

  14. REM sleep behavior disorder in Parkinson's disease: A case from India confirmed with polysomnographic data

    PubMed Central

    Gupta, Ravi; Goel, Deepak; Walker, Jim; Farney, Robert J

    2013-01-01

    Rapid eye movement (REM) sleep behavior disorder is a condition characterized by dream enactment. This condition may accompany neurodegenerative disorders. However, only a few reports from India are available, that too, without any polysomnographic evidence. We are reporting a case of REM sleep behavior disorder with polysomnographic evidence. PMID:24174810

  15. The supramammillary nucleus and the claustrum activate the cortex during REM sleep.

    PubMed

    Renouard, Leslie; Billwiller, Francesca; Ogawa, Keiko; Clément, Olivier; Camargo, Nutabi; Abdelkarim, Mouaadh; Gay, Nadine; Scoté-Blachon, Céline; Touré, Rouguy; Libourel, Paul-Antoine; Ravassard, Pascal; Salvert, Denise; Peyron, Christelle; Claustrat, Bruno; Léger, Lucienne; Salin, Paul; Malleret, Gael; Fort, Patrice; Luppi, Pierre-Hervé

    2015-04-01

    Evidence in humans suggests that limbic cortices are more active during rapid eye movement (REM or paradoxical) sleep than during waking, a phenomenon fitting with the presence of vivid dreaming during this state. In that context, it seemed essential to determine which populations of cortical neurons are activated during REM sleep. Our aim in the present study is to fill this gap by combining gene expression analysis, functional neuroanatomy, and neurochemical lesions in rats. We find in rats that, during REM sleep hypersomnia compared to control and REM sleep deprivation, the dentate gyrus, claustrum, cortical amygdaloid nucleus, and medial entorhinal and retrosplenial cortices are the only cortical structures containing neurons with an increased expression of Bdnf, FOS, and ARC, known markers of activation and/or synaptic plasticity. Further, the dentate gyrus is the only cortical structure containing more FOS-labeled neurons during REM sleep hypersomnia than during waking. Combining FOS staining, retrograde labeling, and neurochemical lesion, we then provide evidence that FOS overexpression occurring in the cortex during REM sleep hypersomnia is due to projections from the supramammillary nucleus and the claustrum. Our results strongly suggest that only a subset of cortical and hippocampal neurons are activated and display plasticity during REM sleep by means of ascending projections from the claustrum and the supramammillary nucleus. Our results pave the way for future studies to identify the function of REM sleep with regard to dreaming and emotional memory processing. PMID:26601158

  16. The supramammillary nucleus and the claustrum activate the cortex during REM sleep.

    PubMed

    Renouard, Leslie; Billwiller, Francesca; Ogawa, Keiko; Clément, Olivier; Camargo, Nutabi; Abdelkarim, Mouaadh; Gay, Nadine; Scoté-Blachon, Céline; Touré, Rouguy; Libourel, Paul-Antoine; Ravassard, Pascal; Salvert, Denise; Peyron, Christelle; Claustrat, Bruno; Léger, Lucienne; Salin, Paul; Malleret, Gael; Fort, Patrice; Luppi, Pierre-Hervé

    2015-04-01

    Evidence in humans suggests that limbic cortices are more active during rapid eye movement (REM or paradoxical) sleep than during waking, a phenomenon fitting with the presence of vivid dreaming during this state. In that context, it seemed essential to determine which populations of cortical neurons are activated during REM sleep. Our aim in the present study is to fill this gap by combining gene expression analysis, functional neuroanatomy, and neurochemical lesions in rats. We find in rats that, during REM sleep hypersomnia compared to control and REM sleep deprivation, the dentate gyrus, claustrum, cortical amygdaloid nucleus, and medial entorhinal and retrosplenial cortices are the only cortical structures containing neurons with an increased expression of Bdnf, FOS, and ARC, known markers of activation and/or synaptic plasticity. Further, the dentate gyrus is the only cortical structure containing more FOS-labeled neurons during REM sleep hypersomnia than during waking. Combining FOS staining, retrograde labeling, and neurochemical lesion, we then provide evidence that FOS overexpression occurring in the cortex during REM sleep hypersomnia is due to projections from the supramammillary nucleus and the claustrum. Our results strongly suggest that only a subset of cortical and hippocampal neurons are activated and display plasticity during REM sleep by means of ascending projections from the claustrum and the supramammillary nucleus. Our results pave the way for future studies to identify the function of REM sleep with regard to dreaming and emotional memory processing.

  17. The Significance of REM Sleep on Routine EEG.

    PubMed

    Gangadhara, Shreyas; Pizarro-Otero, Jose; Bozorg, Ali; Benbadis, Selim

    2016-03-01

    The objective of this study was to report on sleep-onset REM period (SOREMP) during routine EEG and conditions associated with it at a comprehensive epilepsy program. We retrospectively reviewed all outpatient and inpatient EEGs performed at Tampa General Hospital, a comprehensive epilepsy center over a four-month period. All EEGs were reviewed by experienced board-certified epileptologists. When SOREMP was identified, the chart was reviewed to identify the most likely etiology and the associated conditions that might be contributing. A total of 449 EEGs were reviewed between August 10, 2009, and December 9, 2009. Of those, 106 were outpatient EEGs and 343 were inpatient EEGs. There were 7 EEGs with SOREMP identified, 6 from inpatient EEGs, and 1 from an outpatient EEG. Thus, SOREMP was more common in the inpatinent setting than outpatient. There is an association of SOREMP with sleep deprivation and drug withdrawal. PMID:27180506

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

    PubMed

    Grözinger, Michael; Kögel, Pia; Röschke, Joachim

    2002-01-01

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

  19. Cold exposure impairs dark-pulse capacity to induce REM sleep in the albino rat.

    PubMed

    Baracchi, Francesca; Zamboni, Giovanni; Cerri, Matteo; Del Sindaco, Elide; Dentico, Daniela; Jones, Christine Ann; Luppi, Marco; Perez, Emanuele; Amici, Roberto

    2008-06-01

    In the albino rat, a REM sleep (REMS) onset can be induced with a high probability and a short latency when the light is suddenly turned off (dark pulse, DP) during non-REM sleep (NREMS). The aim of this study was to investigate to what extent DP delivery could overcome the integrative thermoregulatory mechanisms that depress REMS occurrence during exposure to low ambient temperature (Ta). To this aim, the efficiency of a non-rhythmical repetitive DP (3 min each) delivery during the first 6-h light period of a 12 h:12 h light-dark cycle in inducing REMS was studied in the rat, through the analysis of electroencephalogram, electrocardiogram, hypothalamic temperature and motor activity at different Tas. The results showed that DP delivery triggers a transition from NREMS to REMS comparable to that which occurs spontaneously. However, the efficiency of DP delivery in inducing REMS was reduced during cold exposure to an extent comparable with that observed in spontaneous REMS occurrence. Such impairment was associated with low Delta activity and high sympathetic tone when DPs were delivered. Repetitive DP administration increased REMS amount during the delivery period and a subsequent negative REMS rebound was observed. In conclusion, DP delivery did not overcome the integrative thermoregulatory mechanisms that depress REMS in the cold. These results underline the crucial physiological meaning of the mutual exclusion of thermoregulatory activation and REMS occurrence, and support the hypothesis that the suspension of the central control of body temperature is a prerequisite for REMS occurrence.

  20. Heart rate variability during carbachol-induced REM sleep and cataplexy.

    PubMed

    Torterolo, Pablo; Castro-Zaballa, Santiago; Cavelli, Matías; Velasquez, Noelia; Brando, Victoria; Falconi, Atilio; Chase, Michael H; Migliaro, Eduardo R

    2015-09-15

    The nucleus pontis oralis (NPO) exerts an executive control over REM sleep. Cholinergic input to the NPO is critical for REM sleep generation. In the cat, a single microinjection of carbachol (a cholinergic agonist) into the NPO produces either REM sleep (REMc) or wakefulness with muscle atonia (cataplexy, CA). In order to study the central control of the heart rate variability (HRV) during sleep, we conducted polysomnographic and electrocardiogram recordings from chronically prepared cats during REMc, CA as well as during sleep and wakefulness. Subsequently, we performed statistical and spectral analyses of the HRV. The heart rate was greater during CA compared to REMc, NREM or REM sleep. Spectral analysis revealed that the low frequency band (LF) power was significantly higher during REM sleep in comparison to REMc and CA. Furthermore, we found that during CA there was a decrease in coupling between the RR intervals plot (tachogram) and respiratory activity. In contrast, compared to natural behavioral states, during REMc and CA there were no significant differences in the HRV based upon the standard deviation of normal RR intervals (SDNN) and the mean squared difference of successive intervals (rMSSD). In conclusion, there were differences in the HRV during naturally-occurring REM sleep compared to REMc. In addition, in spite of the same muscle atonia, the HRV was different during REMc and CA. Therefore, the neuronal network that controls the HRV during REM sleep can be dissociated from the one that generates the muscle atonia during this state. PMID:25997581

  1. The effect of REM sleep deprivation on motivation for food reward.

    PubMed

    Hanlon, Erin C; Andrzejewski, Matthew E; Harder, Bridgette K; Kelley, Ann E; Benca, Ruth M

    2005-08-30

    Prolonged sleep deprivation in rats produces a characteristic syndrome consisting of an increase in food intake yet a decrease in weight. Moreover, the increase in food intake generally precedes the weight loss, suggesting that sleep deprivation may affect appetitive behaviors. Using the multiple platform method to produce rapid eye movement (REM) sleep deprivation, we investigated the effect of REM sleep deprivation (REMSD) on motivation for food reward utilizing food-reinforced operant tasks. In acquisition or maintenance of an operant task, REM sleep-deprived rats, with or without simultaneous food restriction, decreased responding for sucrose pellet reward in comparison to controls, despite the fact that all REM sleep-deprived rats lost weight. Furthermore, the overall response deficit of the REM sleep-deprived rats was due to a within-session decline in responding. REM sleep-deprived rats showed evidence of understanding the contingency of the task comparable to controls throughout deprivation period, suggesting that the decrements in responding were not primarily related to deficits in learning or memory. Rather, REM sleep deprivation appears to alter systems involved in motivational processes, reward, and/or attention.

  2. Heart rate variability during carbachol-induced REM sleep and cataplexy.

    PubMed

    Torterolo, Pablo; Castro-Zaballa, Santiago; Cavelli, Matías; Velasquez, Noelia; Brando, Victoria; Falconi, Atilio; Chase, Michael H; Migliaro, Eduardo R

    2015-09-15

    The nucleus pontis oralis (NPO) exerts an executive control over REM sleep. Cholinergic input to the NPO is critical for REM sleep generation. In the cat, a single microinjection of carbachol (a cholinergic agonist) into the NPO produces either REM sleep (REMc) or wakefulness with muscle atonia (cataplexy, CA). In order to study the central control of the heart rate variability (HRV) during sleep, we conducted polysomnographic and electrocardiogram recordings from chronically prepared cats during REMc, CA as well as during sleep and wakefulness. Subsequently, we performed statistical and spectral analyses of the HRV. The heart rate was greater during CA compared to REMc, NREM or REM sleep. Spectral analysis revealed that the low frequency band (LF) power was significantly higher during REM sleep in comparison to REMc and CA. Furthermore, we found that during CA there was a decrease in coupling between the RR intervals plot (tachogram) and respiratory activity. In contrast, compared to natural behavioral states, during REMc and CA there were no significant differences in the HRV based upon the standard deviation of normal RR intervals (SDNN) and the mean squared difference of successive intervals (rMSSD). In conclusion, there were differences in the HRV during naturally-occurring REM sleep compared to REMc. In addition, in spite of the same muscle atonia, the HRV was different during REMc and CA. Therefore, the neuronal network that controls the HRV during REM sleep can be dissociated from the one that generates the muscle atonia during this state.

  3. REM sleep diversity following the pedunculopontine tegmental nucleus lesion in rat.

    PubMed

    Petrovic, Jelena; Lazic, Katarina; Kalauzi, Aleksandar; Saponjic, Jasna

    2014-09-01

    The aim of this study was to demonstrate that two REM clusters, which emerge following bilateral pedunculopontine tegmental nucleus (PPT) lesions in rats, are two functionally distinct REM states. We performed the experiments in Wistar rats, chronically instrumented for sleep recording. Bilateral PPT lesions were produced by the microinfusion of 100 nl of 0.1M ibotenic acid (IBO). Following a recovery period of 2 weeks, we recorded their sleep for 6h. Bilateral PPT lesions were identified by NADPH - diaphorase histochemistry. We applied Fourier analysis to the signals acquired throughout the 6h recordings, and each 10s epoch was differentiated as a Wake, NREM or REM state. We analyzed the topography of the sleep/wake states architecture and their transition structure, their all state-related EEG microstructures, and the sensorimotor (SMCx) and motor (MCx) cortex REM related cortico-muscular coherences (CMCs). Bilateral PPT lesion in rats increased the likelihood of the emergence of two distinct REM sleep states, specifically expressed within the MCx: REM1 and REM2. Bilateral PPT lesion did not change the sleep/wake states architecture of the SMCx, but pathologically increased the duration of REM1 within the MCx, alongside increasing Wake/REM1/Wake and NREM/REM2/NREM transitions within both cortices. In addition, the augmented total REM SMCx EEG beta amplitude and REM1 MCx EEG theta amplitude was the underlying EEG microstructure pathology. PPT lesion induced REM1 and REM2 are differential states with regard to total EMG power, topographically distinct EEG microstructures, and locomotor drives to nuchal musculature.

  4. Sleep and Arousal Mechanisms in Experimental Epilepsy: Epileptic Components of NREM and Antiepileptic Components of REM Sleep

    ERIC Educational Resources Information Center

    Shouse, M. N.; Scordato, J. C.; Farber, P. R.

    2004-01-01

    Neural generators related to different sleep components have different effects on seizure discharge. These sleep-related systems can provoke seizure discharge propagation during nonrapid eye movement (NREM) sleep and can suppress propagation during REM sleep. Experimental manipulations of discrete physiological components were conducted in feline…

  5. Does more sleep matter? Differential effects of NREM- and REM-dominant sleep on sleepiness and vigilance.

    PubMed

    Neu, D; Mairesse, O; Newell, J; Verbanck, P; Peigneux, P; Deliens, G

    2015-05-01

    We investigated effects of NREM and REM predominant sleep periods on sleepiness and psychomotor performances measured with visual analog scales and the psychomotor vigilance task, respectively. After one week of stable sleep-wake rhythms, 18 healthy sleepers slept 3hours of early sleep and 3hours of late sleep, under polysomnographic control, spaced by two hours of sustained wakefulness between sleep periods in a within subjects split-night, sleep interruption protocol. Power spectra analysis was applied for sleep EEG recordings and sleep phase-relative power proportions were computed for six different frequency bands (delta, theta, alpha, sigma, beta and gamma). Both sleep periods presented with similar sleep duration and efficiency. As expected, phasic NREM and REM predominances were obtained for early and late sleep conditions, respectively. Albeit revealing additive effects of total sleep duration, our results showed a systematic discrepancy between psychomotor performances and sleepiness levels. In addition, sleepiness remained stable throughout sustained wakefulness during both conditions, whereas psychomotor performances even decreased after the second sleep period. Disregarding exchanges for frequency bands in NREM or stability in REM, correlations between outcome measures and EEG power proportions further evidenced directional divergence with respect to sleepiness and psychomotor performances, respectively. Showing that the functional correlation pattern changed with respect to early and late sleep condition, the relationships between EEG power and subjective or behavioral outcomes might however essentially be related to total sleep duration rather than to the phasic predominance of REM or NREM sleep.

  6. 5-HT1A receptor-responsive pedunculopontine tegmental neurons suppress REM sleep and respiratory motor activity.

    PubMed

    Grace, Kevin P; Liu, Hattie; Horner, Richard L

    2012-02-01

    Serotonin type 1A (5-HT(1A)) receptor-responsive neurons in the pedunculopontine tegmental nucleus (PPTn) become maximally active immediately before and during rapid eye movement (REM) sleep. A prevailing model of REM sleep generation indicates that activation of such neurons contributes significantly to the generation of REM sleep, and if correct then inactivation of such neurons ought to suppress REM sleep. We test this hypothesis using bilateral microperfusion of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 μm) into the PPTn; this tool has been shown to selectively silence REM sleep-active PPTn neurons while the activity of wake/REM sleep-active PPTn neurons is unaffected. Contrary to the prevailing model, bilateral microperfusion of 8-OH-DPAT into the PPTn (n = 23 rats) significantly increased REM sleep both as a percentage of the total recording time and sleep time, compared with both within-animal vehicle controls and between-animal time-controls. This increased REM sleep resulted from an increased frequency of REM sleep bouts but not their duration, indicating an effect on mechanisms of REM sleep initiation but not maintenance. Furthermore, an increased proportion of the REM sleep bouts stemmed from periods of low REM sleep drive quantified electrographically. Targeted suppression of 5-HT(1A) receptor-responsive PPTn neurons also increased respiratory rate and respiratory-related genioglossus activity, and increased the frequency and amplitude of the sporadic genioglossus activations occurring during REM sleep. These data indicate that 5-HT(1A) receptor-responsive PPTn neurons normally function to restrain REM sleep by elevating the drive threshold for REM sleep induction, and restrain the expression of respiratory rate and motor activities.

  7. Melanin-Concentrating Hormone (MCH): Role in REM Sleep and Depression.

    PubMed

    Torterolo, Pablo; Scorza, Cecilia; Lagos, Patricia; Urbanavicius, Jessika; Benedetto, Luciana; Pascovich, Claudia; López-Hill, Ximena; Chase, Michael H; Monti, Jaime M

    2015-01-01

    The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons of the lateral sector of the posterior hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR) and median (MR) raphe nuclei, which are involved in the control of sleep and mood. Major Depression (MD) is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability, and anhedonia. A short REM sleep latency (i.e., the interval between sleep onset and the first REM sleep period), as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline) and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons. Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD

  8. Melanin-Concentrating Hormone (MCH): Role in REM Sleep and Depression

    PubMed Central

    Torterolo, Pablo; Scorza, Cecilia; Lagos, Patricia; Urbanavicius, Jessika; Benedetto, Luciana; Pascovich, Claudia; López-Hill, Ximena; Chase, Michael H.; Monti, Jaime M.

    2015-01-01

    The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons of the lateral sector of the posterior hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR) and median (MR) raphe nuclei, which are involved in the control of sleep and mood. Major Depression (MD) is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability, and anhedonia. A short REM sleep latency (i.e., the interval between sleep onset and the first REM sleep period), as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline) and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons. Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD

  9. Diagnostic Thresholds for Quantitative REM Sleep Phasic Burst Duration, Phasic and Tonic Muscle Activity, and REM Atonia Index in REM Sleep Behavior Disorder with and without Comorbid Obstructive Sleep Apnea

    PubMed Central

    McCarter, Stuart J.; St. Louis, Erik K.; Duwell, Ethan J.; Timm, Paul C.; Sandness, David J.; Boeve, Bradley F.; Silber, Michael H.

    2014-01-01

    Objectives: We aimed to determine whether phasic burst duration and conventional REM sleep without atonia (RSWA) methods could accurately diagnose REM sleep behavior disorder (RBD) patients with comorbid OSA. Design: We visually analyzed RSWA phasic burst durations, phasic, “any,” and tonic muscle activity by 3-s mini-epochs, phasic activity by 30-s (AASM rules) epochs, and conducted automated REM atonia index (RAI) analysis. Group RSWA metrics were analyzed and regression models fit, with receiver operating characteristic (ROC) curves determining the best diagnostic cutoff thresholds for RBD. Both split-night and full-night polysomnographic studies were analyzed. Setting: N/A. Participants: Parkinson disease (PD)-RBD (n = 20) and matched controls with (n = 20) and without (n = 20) OSA. Interventions: N/A. Measurements and Results: All mean RSWA phasic burst durations and muscle activities were higher in PD-RBD patients than controls (P < 0.0001), and RSWA associations with PD-RBD remained significant when adjusting for age, gender, and REM AHI (P < 0.0001). RSWA muscle activity (phasic, “any”) cutoffs for 3-s mini-epoch scorings were submentalis (SM) (15.5%, 21.6%), anterior tibialis (AT) (30.2%, 30.2%), and combined SM/AT (37.9%, 43.4%). Diagnostic cutoffs for 30-s epochs (AASM criteria) were SM 2.8%, AT 11.3%, and combined SM/AT 34.7%. Tonic muscle activity cutoff of 1.2% was 100% sensitive and specific, while RAI (SM) cutoff was 0.88. Phasic muscle burst duration cutoffs were: SM (0.65) and AT (0.79) seconds. Combining phasic burst durations with RSWA muscle activity improved sensitivity and specificity of RBD diagnosis. Conclusions: This study provides evidence for REM sleep without atonia diagnostic thresholds applicable in Parkinson disease-REM sleep behavior disorder (PD-RBD) patient populations with comorbid OSA that may be useful toward distinguishing PD-RBD in typical outpatient populations. Citation: McCarter SJ, St. Louis EK, Duwell EJ, Timm PC

  10. REM Sleep-Dependent Bidirectional Regulation of Hippocampal-Based Emotional Memory and LTP.

    PubMed

    Ravassard, Pascal; Hamieh, Al Mahdy; Joseph, Mickaël Antoine; Fraize, Nicolas; Libourel, Paul-Antoine; Lebarillier, Léa; Arthaud, Sébastien; Meissirel, Claire; Touret, Monique; Malleret, Gaël; Salin, Paul-Antoine

    2016-04-01

    Prolonged rapid-eye-movement (REM) sleep deprivation has long been used to study the role of REM sleep in learning and memory processes. However, this method potentially induces stress and fatigue that may directly affect cognitive functions. Here, by using a short-term and nonstressful REM sleep deprivation (RSD) method we assessed in rats the bidirectional influence of reduced and increased REM sleep amount on hippocampal-dependent emotional memory and plasticity. Our results indicate that 4 h RSD impaired consolidation of contextual fear conditioning (CFC) and induction of long-term potentiation (LTP), while decreasing density of Egr1/Zif268-expressing neurons in the CA1 region of the dorsal hippocampus. LTP and Egr1 expression were not affected in ventral CA1. Conversely, an increase in REM sleep restores and further facilitates CFC consolidation and LTP induction, and also increases Egr1 expression in dorsal CA1. Moreover, CFC consolidation, Egr1 neuron density, and LTP amplitude in dorsal CA1 show a positive correlation with REM sleep amount. Altogether, these results indicate that mild changes in REM sleep amount bidirectionally affect memory and synaptic plasticity mechanisms occurring in the CA1 area of the dorsal hippocampus.

  11. Melatonin in patients with reduced REM sleep duration: two randomized controlled trials.

    PubMed

    Kunz, Dieter; Mahlberg, Richard; Müller, Cordula; Tilmann, Amely; Bes, Frederik

    2004-01-01

    Recent data suggest that melatonin may influence human physiology, including the sleep-wake cycle, in a time-dependent manner via the body's internal clock. Rapid-eye-movement (REM) sleep expression is strongly circadian modulated, and the impact of REM sleep on primary brain functions, metabolic processes, and immune system function has become increasingly clear over the past decade. In our study, we evaluated the effects of exogenous melatonin on disturbed REM sleep in humans. Fourteen consecutive outpatients (five women, nine men; mean age, 50 yr) with unselected neuropsychiatric sleep disorders and reduced REM sleep duration (25% or more below age norm according to diagnostic polysomnography) were included in two consecutive, randomized, double-blind, placebo-controlled, parallel design clinical trials. Patients received 3 mg melatonin daily, administered between 2200 and 2300 h for 4 wk. The results of the study show that melatonin was significantly more effective than placebo: patients on melatonin experienced significant increases in REM sleep percentage (baseline/melatonin, 14.7/17.8 vs. baseline/placebo, 14.3/12.0) and improvements in subjective measures of daytime dysfunction as well as clinical global impression score. Melatonin did not shift circadian phase or suppress temperature but did increase REM sleep continuity and promote decline in rectal temperature during sleep. These results were confirmed in patients who received melatonin in the second study (REM sleep percentage baseline/placebo/melatonin, 14.3/12.0/17.9). In patients who received melatonin in the first study and placebo in the second, the above mentioned effects outlasted the period of melatonin administration and diminished only slowly over time (REM sleep percentage baseline/melatonin/placebo, 14.7/17.8/16.2). Our findings show that exogenous melatonin, when administered at the appropriate time, seems to normalize circadian variation in human physiology. It may, therefore, have a

  12. Thermoregulatory adjustments to thermal transients during slow wave sleep and REM sleep in man.

    PubMed

    Libert, J P; Candas, V; Muzet, A; Ehrhart, J

    1982-01-01

    The present study was performed on five nude male subjects by increasing the ambient temperature during well-established slow wave sleep (SWS) and rapid eye movement (REM) sleep episodes. 1. Air temperature was raised from 25 to 41 degrees C at rates of + 0.8 degrees C.min-1 or + 1.6 degrees C min-1 and, afterwards, was maintained at 41 degrees C during 10 min before returning to the initial pre-heating condition. During these thermal transients, wall temperatures (Tw), dew-point temperature (Tdp) and air velocity (Va) were kept constant (Tw = 37.5 degrees C; Tdp = 10 degrees C; Va = 0.3 m.s.-1). Physiological data included 3 EEGs, 2 EOGs, 4 EMGs, heart rate, finger pulse amplitude, esophageal temperature and 10 local skin temperatures. Upper chest sweating rate was recorded by a 12 cm2-capsule using a dew-point hygrometer technique. 2. The results showed that during REM sleep sweat gland activity persists at a lower level than during SWS. The lower sensitivity of the thermoregulatory system described during the REM sleep episodes could be interpreted by an increase of the hypothalamic set-point temperature, or by an action of extra-hypothalamic thermosensitive neurons. However, a change at the sweat gland level cannot be ruled out.

  13. REM and NREM sleep as natural accompaniments of the evolution of warm-bloodedness.

    PubMed

    Lee Kavanau, J

    2002-12-01

    Divergence of primitive sleep into REM and NREM states is thought to have occurred in the nocturnal Triassic ancestors of mammals as a natural accompaniment of the evolution of warm-bloodedness. As ambient temperatures during twilight portions of primitive sleep traversed these evolving ancestors' core temperature, mechanisms of thermoregulatory control that employ muscle contractions became superfluous. The resulting loss of need for such contractions during twilight sleep led to muscle atonia. With muscle tone absent, selection favored the persistence of the fast waves of nocturnal activity during twilight sleep. Stimulations by these waves reinforce motor circuits at the increasing temperatures of evolving warm-bloodedness without leading to sleep-disturbing muscle contractions. By these and related interlinked adaptations, twilight sleep evolved into REM sleep. The daytime period of sleep became NREM sleep. The evolution of NREM and REM sleep following this scenario has implications for sleep's maintenance processes for long-term memories. During NREM sleep, there is an unsynchronized, uncoordinated stimulation and reinforcement of individual distributed component circuits of consolidated memories by slow wave potentials, a process termed 'uncoordinated reinforcement'. The corresponding process during REM sleep is the coordinated stimulation and reinforcement of these circuits by fast wave potentials. This action temporally binds the individual component circuit outputs into fully formed memories, a process termed 'coordinated reinforcement'. Sequential uncoordinated and coordinated reinforcement, that is, NREM followed by REM sleep, emerges as the most effective mechanism of long-term memory maintenance in vertebrates. With the evolution of this two-stage mechanism of long-term memory maintenance, it became adaptive to partition sleep into several NREM-REM cycles, thereby achieving a more lengthy application of the cooperative sequential actions. PMID:12667495

  14. REM and NREM sleep as natural accompaniments of the evolution of warm-bloodedness.

    PubMed

    Lee Kavanau, J

    2002-12-01

    Divergence of primitive sleep into REM and NREM states is thought to have occurred in the nocturnal Triassic ancestors of mammals as a natural accompaniment of the evolution of warm-bloodedness. As ambient temperatures during twilight portions of primitive sleep traversed these evolving ancestors' core temperature, mechanisms of thermoregulatory control that employ muscle contractions became superfluous. The resulting loss of need for such contractions during twilight sleep led to muscle atonia. With muscle tone absent, selection favored the persistence of the fast waves of nocturnal activity during twilight sleep. Stimulations by these waves reinforce motor circuits at the increasing temperatures of evolving warm-bloodedness without leading to sleep-disturbing muscle contractions. By these and related interlinked adaptations, twilight sleep evolved into REM sleep. The daytime period of sleep became NREM sleep. The evolution of NREM and REM sleep following this scenario has implications for sleep's maintenance processes for long-term memories. During NREM sleep, there is an unsynchronized, uncoordinated stimulation and reinforcement of individual distributed component circuits of consolidated memories by slow wave potentials, a process termed 'uncoordinated reinforcement'. The corresponding process during REM sleep is the coordinated stimulation and reinforcement of these circuits by fast wave potentials. This action temporally binds the individual component circuit outputs into fully formed memories, a process termed 'coordinated reinforcement'. Sequential uncoordinated and coordinated reinforcement, that is, NREM followed by REM sleep, emerges as the most effective mechanism of long-term memory maintenance in vertebrates. With the evolution of this two-stage mechanism of long-term memory maintenance, it became adaptive to partition sleep into several NREM-REM cycles, thereby achieving a more lengthy application of the cooperative sequential actions.

  15. The hypocretins (orexins) mediate the “phasic” components of REM sleep: A new hypothesis

    PubMed Central

    Torterolo, Pablo; Chase, Michael H.

    2014-01-01

    In 1998, a group of phenotypically distinct neurons were discovered in the postero-lateral hypothalamus which contained the neuropeptides hypocretin 1 and hypocretin 2 (also called orexin A and orexin B), which are excitatory neuromodulators. Hypocretinergic neurons project throughout the central nervous system and have been involved in the generation and maintenance of wakefulness. The sleep disorder narcolepsy, characterized by hypersomnia and cataplexy, is produced by degeneration of these neurons. The hypocretinergic neurons are active during wakefulness in conjunction with the presence of motor activity that occurs during survival-related behaviors. These neurons decrease their firing rate during non-REM sleep; however there is still controversy upon the activity and role of these neurons during REM sleep. Hence, in the present report we conducted a critical review of the literature of the hypocretinergic system during REM sleep, and hypothesize a possible role of this system in the generation of REM sleep. PMID:26483897

  16. REM sleep and emotional face memory in typically-developing children and children with autism.

    PubMed

    Tessier, Sophie; Lambert, Andréane; Scherzer, Peter; Jemel, Boutheina; Godbout, Roger

    2015-09-01

    Relationship between REM sleep and memory was assessed in 13 neurotypical and 13 children with Autistic Spectrum Disorder (ASD). A neutral/positive/negative face recognition task was administered the evening before (learning and immediate recognition) and the morning after (delayed recognition) sleep. The number of rapid eye movements (REMs), beta and theta EEG activity over the visual areas were measured during REM sleep. Compared to neurotypical children, children with ASD showed more theta activity and longer reaction time (RT) for correct responses in delayed recognition of neutral faces. Both groups showed a positive correlation between sleep and performance but different patterns emerged: in neurotypical children, accuracy for recalling neutral faces and overall RT improvement overnight was correlated with EEG activity and REMs; in children with ASD, overnight RT improvement for positive and negative faces correlated with theta and beta activity, respectively. These results suggest that neurotypical and children with ASD use different sleep-related brain networks to process faces. PMID:26219603

  17. Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain.

    PubMed

    Rukhadze, I; Kamani, H; Kubin, L

    2011-12-01

    In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM sleep. In 8 chronically instrumented rats, we recorded cortical EEG, EMG at sites near the base of the tongue where genioglossal and intrinsic muscle fibers predominate (GG-I), EMG of the geniohyoid (GH) muscle, and N EMG. Sleep-wake states were identified and EMGs quantified relative to their mean levels in wakefulness in successive 10 s epochs. During non-REM sleep, the average EMG levels differed among the three muscles, with the order being N>GH>GG-I. During REM sleep, due to different magnitudes of phasic twitches, the order was reversed to GG-I>GH>N. GG-I and GH exhibited a gradual increase of twitching that peaked at 70-120 s after the onset of REM sleep and then declined if the REM sleep episode lasted longer. We propose that a common phasic excitatory generator impinges on motoneuron pools that innervate different muscles, but twitching magnitudes are different due to different levels of tonic motoneuronal hyperpolarization. We also propose that REM sleep episodes of average durations are terminated by intense activity of the central generator of phasic events, whereas long REM sleep episodes end as a result of a gradual waning of the tonic disfacilitatory and inhibitory processes.

  18. Disruption of endocrine rhythms in sleeping sickness with preserved relationship between hormonal pulsatility and the REM-NREM sleep cycles.

    PubMed

    Brandenberger, G; Buguet, A; Spiegel, K; Stanghellini, A; Muanga, G; Bogui, P; Dumas, M

    1996-09-01

    In human African trypanosomiasis (sleeping sickness), sleep and wake episodes are sporadically distributed throughout the day and the night. To determine whether these sleep disturbances affect the 24-h hormone profiles and the normal relationships between hormone pulsatility and sleep stages, polygraphic sleep recordings and concomitant hormone profiles were obtained in 6 African patients with sleeping sickness and in 5 healthy African subjects selected from Abidjan on the Ivory Coast. Polysomnographic recordings were continuous, and blood was taken every 10 min throughout the 24-h period. Plasma was analyzed for cortisol, prolactin, and plasma renin activity (PRA). The 24-h rhythm of cortisol, considered to be an endogenous circadian rhythm, was attenuated in all of the patients except one. However, as in normal subjects, slow wave sleep (SWS) remained associated with the declining phases of the cortisol secretory episodes. Prolactin and PRA profiles, which are strongly influenced by the sleep-wake cycle, did not manifest the nocturnal increase normally associated with the sleep period; instead, they reflected a sporadic distribution of the sleep and wake episodes throughout the 24-h period. In patients with sleeping sickness as in normal subjects, rapid eye movement (REM) sleep began during the descending phases of prolactin pulses. In both groups, PRA reflected the sleep stage distribution with non REM (NREM) sleep occurring during the ascending phases and REM sleep during the descending phases of the PRA oscillations. However, in sleeping sickness patients, the marked sleep fragmentation often did not allow sufficient time for PRA to increase significantly, as is normally the case in subjects with regular NREM-REM sleep cycles. These results demonstrate that, together with the disruption of the sleep-wake cycle, there are profound differences in the temporal organization of the 24-h hormone profiles in humans with African trypanosomiasis. However, the

  19. REM sleep deprivation reduces auditory evoked inhibition of dorsolateral pontine neurons.

    PubMed

    Mallick, B N; Fahringer, H M; Wu, M F; Siegel, J M

    1991-06-28

    In many dorsolateral pontine neurons, auditory stimulation produces an initial excitation followed by a sustained inhibition. We now report that rapid eye movement (REM) sleep deprivation, for periods of from 22-48 h, reduced this auditory evoked inhibition of unit discharge. Inhibition returned to baseline levels after recovery REM sleep. Prior work indicates that the auditory evoked inhibition seen in noradrenergic cells in this region is partially mediated by norepinephrine. We hypothesize that the reduction in inhibition that we see is a consequence of either downregulation/desensitization of norepinephrine receptors or reduced norepinephrine release resulting from REM sleep deprivation. PMID:1913194

  20. REM sleep loss and recovery regulates blood-brain barrier function.

    PubMed

    Gómez-González, Beatriz; Hurtado-Alvarado, Gabriela; Esqueda-León, Enrique; Santana-Miranda, Rafael; Rojas-Zamorano, José Ángel; Velázquez-Moctezuma, Javier

    2013-08-01

    The functions of rapid eye movement (REM) sleep have remained elusive since more than 50 years. Previous reports have identified several independent processes affected by the loss and subsequent recovery of REM sleep (hippocampal neurogenesis, brain stem neuronal cell death, and neurotransmitter content in several brain regions); however, a common underlying mechanism has not been found. We propose that altered brain homeostasis secondary to blood-brain barrier breakdown may explain all those changes induced by REM sleep loss. Therefore, the present report aimed to study the consequences of REM sleep restriction upon blood-brain barrier permeability to Evans blue. REM sleep restriction was induced by the multiple platform technique; male rats were REM sleep restricted 20h daily (with 4h sleep opportunity) during 10 days; control groups included large platform and intact rats. To study blood-brain barrier permeability Evans blue was intracardially administered; stained brains were sliced and photographed for optical density quantification. An independent experiment was carried out to elucidate the mechanism of blood-brain breakdown by transmission electron microscopy. REM sleep restriction increased blood-brain barrier permeability to Evans blue in the whole brain as compared to both control groups. Brief periods of sleep recovery rapidly and effectively restored the severe alteration of blood-brain barrier function by reducing blood-to-brain transfer of Evans blue. The mechanism of blood-brain barrier breakdown involved increased caveolae formation at brain endothelial cells. In conclusion, our data suggest that REM sleep regulates the physical barrier properties of the blood-brain barrier.

  1. Altered Sleep Stage Transitions of REM Sleep: A Novel and Stable Biomarker of Narcolepsy

    PubMed Central

    Liu, Yaping; Zhang, Jihui; Lam, Venny; Ho, Crover Kwok Wah; Zhou, Junying; Li, Shirley Xin; Lam, Siu Ping; Yu, Mandy Wai Man; Tang, Xiangdong; Wing, Yun-Kwok

    2015-01-01

    Objectives: To determine the diagnostic values, longitudinal stability, and HLA association of the sleep stage transitions in narcolepsy. Methods: To compare the baseline differences in the sleep stage transition to REM sleep among 35 patients with type 1 narcolepsy, 39 patients with type 2 narcolepsy, 26 unaffected relatives, and 159 non-narcoleptic sleep patient controls, followed by a reassessment at a mean duration of 37.4 months. Results: The highest prevalence of altered transition from stage non-N2/N3 to stage R in multiple sleep latency test (MSLT) and nocturnal polysomnography (NPSG) was found in patients with type 1 narcolepsy (92.0% and 57.1%), followed by patients with type 2 narcolepsy (69.4% and 12.8%), unaffected relatives (46.2% and 0%), and controls (39.3% and 1.3%). Individual sleep variables had varied sensitivity and specificity in diagnosing narcolepsy. By incorporating a combination of sleep variables, the decision tree analysis improved the sensitivity to 94.3% and 82.1% and enhanced specificity to 82.4% and 83% for the diagnosis of type 1 and type 2 narcolepsy, respectively. There was a significant association of DBQ1*0602 with the altered sleep stage transition (OR = 16.0, 95% CI: 1.7–149.8, p = 0.015). The persistence of the altered sleep stage transition in both MSLT and NPSG was high for both type 1 (90.5% and 64.7%) and type 2 narcolepsy (92.3% and 100%), respectively. Conclusions: Altered sleep stage transition is a significant and stable marker of narcolepsy, which suggests a vulnerable wake-sleep dysregulation trait in narcolepsy. Altered sleep stage transition has a significant diagnostic value in the differential diagnosis of hypersomnias, especially when combined with other diagnostic sleep variables in decision tree analysis. Citation: Liu Y, Zhang J, Lam V, Ho CK, Zhou J, Li SX, Lam SP, Yu MW, Tang X, Wing YK. Altered sleep stage transitions of REM sleep: a novel and stable biomarker of narcolepsy. J Clin Sleep Med 2015

  2. Enhanced emotional reactivity after selective REM sleep deprivation in humans: an fMRI study

    PubMed Central

    Rosales-Lagarde, Alejandra; Armony, Jorge L.; del Río-Portilla, Yolanda; Trejo-Martínez, David; Conde, Ruben; Corsi-Cabrera, Maria

    2012-01-01

    Converging evidence from animal and human studies suggest that rapid eye movement (REM) sleep modulates emotional processing. The aim of the present study was to explore the effects of selective REM sleep deprivation (REM-D) on emotional responses to threatening visual stimuli and their brain correlates using functional magnetic resonance imaging (fMRI). Twenty healthy subjects were randomly assigned to two groups: selective REM-D, by awakening them at each REM sleep onset, or non-rapid eye movement sleep interruptions (NREM-I) as control for potential non-specific effects of awakenings and lack of sleep. In a within-subject design, a visual emotional reactivity task was performed in the scanner before and 24 h after sleep manipulation. Behaviorally, emotional reactivity was enhanced relative to baseline (BL) in the REM deprived group only. In terms of fMRI signal, there was, as expected, an overall decrease in activity in the NREM-I group when subjects performed the task the second time, particularly in regions involved in emotional processing, such as occipital and temporal areas, as well as in the ventrolateral prefrontal cortex, involved in top-down emotion regulation. In contrast, activity in these areas remained the same level or even increased in the REM-D group, compared to their BL level. Taken together, these results suggest that lack of REM sleep in humans is associated with enhanced emotional reactivity, both at behavioral and neural levels, and thus highlight the specific role of REM sleep in regulating the neural substrates for emotional responsiveness. PMID:22719723

  3. Enhanced emotional reactivity after selective REM sleep deprivation in humans: an fMRI study.

    PubMed

    Rosales-Lagarde, Alejandra; Armony, Jorge L; Del Río-Portilla, Yolanda; Trejo-Martínez, David; Conde, Ruben; Corsi-Cabrera, Maria

    2012-01-01

    Converging evidence from animal and human studies suggest that rapid eye movement (REM) sleep modulates emotional processing. The aim of the present study was to explore the effects of selective REM sleep deprivation (REM-D) on emotional responses to threatening visual stimuli and their brain correlates using functional magnetic resonance imaging (fMRI). Twenty healthy subjects were randomly assigned to two groups: selective REM-D, by awakening them at each REM sleep onset, or non-rapid eye movement sleep interruptions (NREM-I) as control for potential non-specific effects of awakenings and lack of sleep. In a within-subject design, a visual emotional reactivity task was performed in the scanner before and 24 h after sleep manipulation. Behaviorally, emotional reactivity was enhanced relative to baseline (BL) in the REM deprived group only. In terms of fMRI signal, there was, as expected, an overall decrease in activity in the NREM-I group when subjects performed the task the second time, particularly in regions involved in emotional processing, such as occipital and temporal areas, as well as in the ventrolateral prefrontal cortex, involved in top-down emotion regulation. In contrast, activity in these areas remained the same level or even increased in the REM-D group, compared to their BL level. Taken together, these results suggest that lack of REM sleep in humans is associated with enhanced emotional reactivity, both at behavioral and neural levels, and thus highlight the specific role of REM sleep in regulating the neural substrates for emotional responsiveness.

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

    PubMed

    Maruthai, Nirmala; Nagendra, Ravindra P; Sasidharan, Arun; Srikumar, Sulekha; Datta, Karuna; Uchida, Sunao; Kutty, Bindu M

    2016-06-01

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

  5. The 'scanning hypothesis' of rapid eye movements during REM sleep: a review of the evidence.

    PubMed

    Arnulf, I

    2011-12-01

    Rapid eye movements (REMs) and visual dreams are salient features of REM sleep. However, it is unclear whether the eyes scan dream images. Several lines of evidence oppose the scanning hypothesis: REMs persist in animals and humans without sight (pontine cats, foetus, neonates, born-blinds), some binocular REMs are not conjugated (no focus point), REMs occur in parallel (not in series) with the stimulation of the visual cortex by ponto-geniculo-occipital spikes, and visual dreams can be obtained in non REM sleep. Studies that retrospectively compared the direction of REMs to dream recall recorded after having awakened the sleeper yielded inconsistent results, with a concordance varying from 9 to 80%. However, this method was subject to methodological flaws, including the bias of retrospection and neck atonia that does not allow the determination of the exact direction of gaze. Using the model of RBD (in which patients are able to enact their dreams due to the absence of muscle atonia) in 56 patients, we directly determined if the eyes moved in the same directions as the head and limbs. When REMs accompanied goal-oriented motor behaviour during RBD (e.g., framing something, greeting with the hand, climbing a ladder), 90% were directed towards the action of the patient (same plane and direction). REMs were however absent in 38% of goal-oriented behaviours. This directional coherence between limbs, head and eye movements during RBD suggests that, when present, REMs imitate the scanning of the dream scene. Because REMs index and complexity were similar in patients with RBD and controls, this concordance can be extended to normal REM sleep. These results are consistent with the model of a brainstem generator activating simultaneously images, sounds, limbs movements and REMs in a coordinated parallel manner, as in a virtual reality.

  6. The 'scanning hypothesis' of rapid eye movements during REM sleep: a review of the evidence.

    PubMed

    Arnulf, I

    2011-12-01

    Rapid eye movements (REMs) and visual dreams are salient features of REM sleep. However, it is unclear whether the eyes scan dream images. Several lines of evidence oppose the scanning hypothesis: REMs persist in animals and humans without sight (pontine cats, foetus, neonates, born-blinds), some binocular REMs are not conjugated (no focus point), REMs occur in parallel (not in series) with the stimulation of the visual cortex by ponto-geniculo-occipital spikes, and visual dreams can be obtained in non REM sleep. Studies that retrospectively compared the direction of REMs to dream recall recorded after having awakened the sleeper yielded inconsistent results, with a concordance varying from 9 to 80%. However, this method was subject to methodological flaws, including the bias of retrospection and neck atonia that does not allow the determination of the exact direction of gaze. Using the model of RBD (in which patients are able to enact their dreams due to the absence of muscle atonia) in 56 patients, we directly determined if the eyes moved in the same directions as the head and limbs. When REMs accompanied goal-oriented motor behaviour during RBD (e.g., framing something, greeting with the hand, climbing a ladder), 90% were directed towards the action of the patient (same plane and direction). REMs were however absent in 38% of goal-oriented behaviours. This directional coherence between limbs, head and eye movements during RBD suggests that, when present, REMs imitate the scanning of the dream scene. Because REMs index and complexity were similar in patients with RBD and controls, this concordance can be extended to normal REM sleep. These results are consistent with the model of a brainstem generator activating simultaneously images, sounds, limbs movements and REMs in a coordinated parallel manner, as in a virtual reality. PMID:22205589

  7. Brain structures and mechanisms involved in the generation of REM sleep.

    PubMed

    Reinoso-Suárez, Fernando; de Andrés, Isabel; Rodrigo-Angulo, Margarita L.; Garzón, Miguel

    2001-02-01

    This article reviews the central nervous mechanisms involved in the broad network that generates and maintains REM sleep. Experimental investigations have identified the pontine tegmentum as the critical substrate for REM sleep mechanisms. Several pontine structures are involved in the generation of each particular polygraphic event that characterizes REM sleep: desynchronization in the electroencephalogram, theta rhythm in the hippocampus, muscle atonia, pontogeniculooccipital waves and rapid eye movements. The pontine tegmentum also holds the region where cholinergic stimulation can trigger all the behavioural and bioelectric signs of REM sleep. The exact location has been investigated and amply discussed over the last few years. Studies in the authors> laboratory, mapping the pontine tegmentum with small volume carbachol (a cholinergic agonist) microinjections, have demonstrated that the executive neurons for REM sleep generation are neither located in the dorsal part of the pontine tegmentum, nor diffusely spread through the medial pontine reticular formation: they are concentrated in a discrete area in the ventral part of the oral pontine reticular nucleus (vRPO). In turn, the vRPO has connections with structures involved in the generation of the other states of the sleep-wake cycle as well as with structures responsible for the generation of each of the different events characterizing REM sleep. This allows us to propose the vRPO as the crucial region for REM sleep generation. Related research, with invivo and invitro experiments, into the actions of different neurotransmitters on vRPO neurones indicates that not only acetylcholine but other neurotransmitters have an active key role in vRPO REM sleep generation mechanisms.

  8. No effect of odor-induced memory reactivation during REM sleep on declarative memory stability

    PubMed Central

    Cordi, Maren J.; Diekelmann, Susanne; Born, Jan; Rasch, Björn

    2014-01-01

    Memory reactivations in hippocampal brain areas are critically involved in memory consolidation processes during sleep. In particular, specific firing patterns of hippocampal place cells observed during learning are replayed during subsequent sleep and rest in rodents. In humans, experimentally inducing hippocampal memory reactivations during slow-wave sleep (but not during wakefulness) benefits consolidation and immediately stabilizes declarative memories against future interference. Importantly, spontaneous hippocampal replay activity can also be observed during rapid eye movement (REM) sleep and some authors have suggested that replay during REM sleep is related to processes of memory consolidation. However, the functional role of reactivations during REM sleep for memory stability is still unclear. Here, we reactivated memories during REM sleep and examined its consequences for the stability of declarative memories. After 3 h of early, slow-wave sleep (SWS) rich sleep, 16 healthy young adults learned a 2-D object location task in the presence of a contextual odor. During subsequent REM sleep, participants were either re-exposed to the odor or to an odorless vehicle, in a counterbalanced within subject design. Reactivation was followed by an interference learning task to probe memory stability after awakening. We show that odor-induced memory reactivation during REM sleep does not stabilize memories against future interference. We propose that the beneficial effect of reactivation during sleep on memory stability might be critically linked to processes characterizing SWS including, e.g., slow oscillatory activity, sleep spindles, or low cholinergic tone, which are required for a successful redistribution of memories from medial temporal lobe regions to neocortical long-term stores. PMID:25225474

  9. Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man.

    PubMed

    Gotter, Anthony L; Forman, Mark S; Harrell, Charles M; Stevens, Joanne; Svetnik, Vladimir; Yee, Ka Lai; Li, Xiaodong; Roecker, Anthony J; Fox, Steven V; Tannenbaum, Pamela L; Garson, Susan L; Lepeleire, Inge De; Calder, Nicole; Rosen, Laura; Struyk, Arie; Coleman, Paul J; Herring, W Joseph; Renger, John J; Winrow, Christopher J

    2016-01-01

    Orexin neuropeptides regulate sleep/wake through orexin receptors (OX1R, OX2R); OX2R is the predominant mediator of arousal promotion. The potential for single OX2R antagonism to effectively promote sleep has yet to be demonstrated in humans. MK-1064 is an OX2R-single antagonist. Preclinically, MK-1064 promotes sleep and increases both rapid eye movement (REM) and non-REM (NREM) sleep in rats at OX2R occupancies higher than the range observed for dual orexin receptor antagonists. Similar to dual antagonists, MK-1064 increases NREM and REM sleep in dogs without inducing cataplexy. Two Phase I studies in healthy human subjects evaluated safety, tolerability, pharmacokinetics and sleep-promoting effects of MK-1064, and demonstrated dose-dependent increases in subjective somnolence (via Karolinska Sleepiness Scale and Visual Analogue Scale measures) and sleep (via polysomnography), including increased REM and NREM sleep. Thus, selective OX2R antagonism is sufficient to promote REM and NREM sleep across species, similarly to that seen with dual orexin receptor antagonism. PMID:27256922

  10. Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man.

    PubMed

    Gotter, Anthony L; Forman, Mark S; Harrell, Charles M; Stevens, Joanne; Svetnik, Vladimir; Yee, Ka Lai; Li, Xiaodong; Roecker, Anthony J; Fox, Steven V; Tannenbaum, Pamela L; Garson, Susan L; Lepeleire, Inge De; Calder, Nicole; Rosen, Laura; Struyk, Arie; Coleman, Paul J; Herring, W Joseph; Renger, John J; Winrow, Christopher J

    2016-01-01

    Orexin neuropeptides regulate sleep/wake through orexin receptors (OX1R, OX2R); OX2R is the predominant mediator of arousal promotion. The potential for single OX2R antagonism to effectively promote sleep has yet to be demonstrated in humans. MK-1064 is an OX2R-single antagonist. Preclinically, MK-1064 promotes sleep and increases both rapid eye movement (REM) and non-REM (NREM) sleep in rats at OX2R occupancies higher than the range observed for dual orexin receptor antagonists. Similar to dual antagonists, MK-1064 increases NREM and REM sleep in dogs without inducing cataplexy. Two Phase I studies in healthy human subjects evaluated safety, tolerability, pharmacokinetics and sleep-promoting effects of MK-1064, and demonstrated dose-dependent increases in subjective somnolence (via Karolinska Sleepiness Scale and Visual Analogue Scale measures) and sleep (via polysomnography), including increased REM and NREM sleep. Thus, selective OX2R antagonism is sufficient to promote REM and NREM sleep across species, similarly to that seen with dual orexin receptor antagonism.

  11. Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man

    PubMed Central

    Gotter, Anthony L.; Forman, Mark S.; Harrell, Charles M.; Stevens, Joanne; Svetnik, Vladimir; Yee, Ka Lai; Li, Xiaodong; Roecker, Anthony J.; Fox, Steven V.; Tannenbaum, Pamela L.; Garson, Susan L.; Lepeleire, Inge De; Calder, Nicole; Rosen, Laura; Struyk, Arie; Coleman, Paul J.; Herring, W. Joseph; Renger, John J.; Winrow, Christopher J.

    2016-01-01

    Orexin neuropeptides regulate sleep/wake through orexin receptors (OX1R, OX2R); OX2R is the predominant mediator of arousal promotion. The potential for single OX2R antagonism to effectively promote sleep has yet to be demonstrated in humans. MK-1064 is an OX2R-single antagonist. Preclinically, MK-1064 promotes sleep and increases both rapid eye movement (REM) and non-REM (NREM) sleep in rats at OX2R occupancies higher than the range observed for dual orexin receptor antagonists. Similar to dual antagonists, MK-1064 increases NREM and REM sleep in dogs without inducing cataplexy. Two Phase I studies in healthy human subjects evaluated safety, tolerability, pharmacokinetics and sleep-promoting effects of MK-1064, and demonstrated dose-dependent increases in subjective somnolence (via Karolinska Sleepiness Scale and Visual Analogue Scale measures) and sleep (via polysomnography), including increased REM and NREM sleep. Thus, selective OX2R antagonism is sufficient to promote REM and NREM sleep across species, similarly to that seen with dual orexin receptor antagonism. PMID:27256922

  12. Differential impact of REM sleep deprivation on cytoskeletal proteins of brain regions involved in sleep regulation.

    PubMed

    Rodríguez-Vázquez, Jennifer; Camacho-Arroyo, Ignacio; Velázquez-Moctezuma, Javier

    2012-01-01

    Rapid eye movement (REM) sleep is involved in memory consolidation, which implies synaptic plasticity. This process requires protein synthesis and the reorganization of the neural cytoskeleton. REM sleep deprivation (REMSD) has an impact on some neuronal proteins involved in synaptic plasticity, such as glutamate receptors and postsynaptic density protein 95, but its effects on cytoskeletal proteins is unknown. In this study, the effects of REMSD on the content of the cytoskeletal proteins MAP2 and TAU were analyzed. Adult female rats were submitted to selective REMSD by using the multiple platform technique. After 24, 48 or 72 h of REMSD, rats were decapitated and the following brain areas were dissected: pons, preoptic area, hippocampus and frontal cortex. Protein extraction and Western blot were performed. Results showed an increase in TAU content in the pons, preoptic area and hippocampus after 24 h of REMSD, while in the frontal cortex a significant increase in TAU content was observed after 72 h of REMSD. A TAU content decrease was observed in the hippocampus after 48 h of REMSD. Interestingly, a marked increase in TAU content was observed after 72 h of REMSD. MAP2 content only increased in the preoptic area at 24 h, and in the frontal cortex after 24 and 72 h of REMSD, without significant changes in the pons and hippocampus. These results support the idea that REM sleep plays an important role in the organization of neural cytoskeleton, and that this effect is tissue-specific.

  13. Post-learning REM sleep deprivation impairs long-term memory: reversal by acute nicotine treatment.

    PubMed

    Aleisa, A M; Alzoubi, K H; Alkadhi, K A

    2011-07-15

    Rapid eye movement sleep deprivation (REM-SD) is associated with spatial learning and memory impairment. During REM-SD, an increase in nicotine consumption among habitual smokers and initiation of tobacco use by non-smokers have been reported. We have shown recently that nicotine treatment prevented learning and memory impairments associated with REM-SD. We now report the interactive effects of post-learning REM-SD and/or nicotine. The animals were first trained on the radial arm water maze (RAWM) task, then they were REM-sleep deprived using the modified multiple platform paradigm for 24h. During REM-SD period, the rats were injected with saline or nicotine (1mg/kg s.c. every 12h: a total of 3 injections). The animals were tested for long-term memory in the RAWM at the end of the REM-SD period. The 24h post-learning REM-SD significantly impaired long-term memory. However, nicotine treatment reversed the post-learning REM-SD-induced impairment of long-term memory. On the other hand, post-learning treatment of normal rats with nicotine for 24h enhanced long-term memory. These results indicate that post-learning acute nicotine treatment prevented the deleterious effect of REM-SD on cognitive abilities.

  14. Periodic leg movements and REM sleep without atonia in Parkinson's disease with camptocormia.

    PubMed

    Lavault, Sophie; Bloch, Frederic; Houeto, Jean-Luc; Konofal, Eric; Welter, Marie-Laure; Agid, Yves; Arnulf, Isabelle

    2009-12-15

    Camptocormia (a flexion of the trunk that only appears when standing or walking) affects a minority of patients with Parkinson's disease (PD). As it responds poorly to levodopa and is associated with reduced midbrain and pons volume, it may result from non-dopaminergic, brainstem lesions. As several sleep abnormalities in PD also result from non-dopaminergic brainstem lesions, we monitored sleep in 24 non-demented PD patients with (n = 12) and without (n = 12) camptocormia and in 12 controls. Nearly half (42%) patients with camptocormia had abnormal periodic leg movement indices (>15/h), versus 17% patients without camptocormia and 8% of controls (p = 0.02). In addition, the percentage of enhanced muscle activity during REM sleep (measured on the chin and on the limb muscles) tended to be higher in patients with than without camptocormia (51 +/- 39% vs. 20 +/- 25%, p = 0.06). The other sleep and REM sleep characteristics (sleep and REM sleep onset latencies, sleep time and sleep stage percentages, REMs density, arousal, and apnea-hypopnea indices) were not different between these two PD groups. Lesions causing this axial dystonia may spare the sleep systems but affect the control of movements during sleep. PMID:19891002

  15. GABA(A) receptors implicated in REM sleep control express a benzodiazepine binding site.

    PubMed

    Nguyen, Tin Quang; Liang, Chang-Lin; Marks, Gerald A

    2013-08-21

    It has been reported that non-subtype-selective GABAA receptor antagonists injected into the nucleus pontis oralis (PnO) of rats induced long-lasting increases in REM sleep. Characteristics of these REM sleep increases were identical to those resulting from injection of muscarinic cholinergic agonists. Both actions were blocked by the muscarinic antagonist, atropine. Microdialysis of GABAA receptor antagonists into the PnO resulted in increased acetylcholine levels. These findings were consistent with GABAA receptor antagonists disinhibiting acetylcholine release in the PnO to result in an acetylcholine-mediated REM sleep induction. Direct evidence has been lacking for localization in the PnO of the specific GABAA receptor-subtypes mediating the REM sleep effects. Here, we demonstrated a dose-related, long-lasting increase in REM sleep following injection (60 nl) in the PnO of the inverse benzodiazepine agonist, methyl-6,7-dimethoxy-4-ethyl-β-carboline (DMCM, 10(-2)M). REM sleep increases were greater and more consistently produced than with the non-selective antagonist gabazine, and both were blocked by atropine. Fluorescence immunohistochemistry and laser scanning confocal microscopy, colocalized in PnO vesicular acetylcholine transporter, a presynaptic marker of cholinergic boutons, with the γ2 subunit of the GABAA receptor. These data provide support for the direct action of GABA on mechanisms of acetylcholine release in the PnO. The presence of the γ2 subunit at this locus and the REM sleep induction by DMCM are consistent with binding of benzodiazepines by a GABAA receptor-subtype in control of REM sleep.

  16. REM sleep modulation by perifornical orexinergic inputs to the pedunculo-pontine tegmental neurons in rats.

    PubMed

    Khanday, M A; Mallick, B N

    2015-11-12

    Rapid eye movement sleep (REMS) is regulated by the interaction of the REM-ON and REM-OFF neurons located in the pedunculo-pontine-tegmentum (PPT) and the locus coeruleus (LC), respectively. Many other brain areas, particularly those controlling non-REMS (NREMS) and waking, modulate REMS by modulating these REMS-related neurons. Perifornical (PeF) orexin (Ox)-ergic neurons are reported to increase waking and reduce NREMS as well as REMS; dysfunction of the PeF neurons are related to REMS loss-associated disorders. Hence, we were interested in understanding the neural mechanism of PeF-induced REMS modulation. As a first step we have recently reported that PeF Ox-ergic neurons modulate REMS by influencing the LC neurons (site for REM-OFF neurons). Thereafter, in this in vivo study we have explored the role of PeF inputs on the PPT neurons (site for REM-ON neurons) for the regulation of REMS. Chronic male rats were surgically prepared with implanted bilateral cannulae in PeF and PPT and electrodes for recording sleep-waking patterns. After post-surgical recovery sleep-waking-REMS were recorded when bilateral PeF neurons were stimulated by glutamate and simultaneously bilateral PPT neurons were infused with either saline or orexin receptor1 (OX1R) antagonist. It was observed that PeF stimulation increased waking and decreased NREMS as well as REMS, which were prevented by OX1R antagonist into the PPT. We conclude that the PeF stimulation-induced reduction in REMS was likely to be due to inhibition of REM-ON neurons in the PPT. As waking and NREMS are inversely related, subject to confirmation, the reduction in NREMS could be due to increased waking or vice versa. Based on our findings from this and earlier studies we have proposed a model showing connections between PeF- and PPT-neurons for REMS regulation.

  17. Shorter REM latency associated with more sleep cycles of a shorter duration in healthy humans.

    PubMed

    Le Bon, O; Staner, L; Hoffmann, G; Kentos, M; Pelc, I; Linkowski, P

    2001-10-10

    A significant association between rapid eye movement (REM) sleep latency and the number of non-REM/REM sleep cycles was found 15 years ago in a large retrospective study. The present prospective study further explored this intra-sleep relationship and analyzed the links between these two variables and the mean cycle duration. It was based on a carefully selected group of healthy control subjects whose sleep was polysomnographically recorded at home for 4 sequential nights. The latency of REM sleep was inversely correlated with the number of cycles and positively correlated with the mean cycle duration, both in individual nights and on means of 4 nights. The present study demonstrated that variations in the number of cycles or the mean cycle duration between the nights are far less important than the substantial differences observed between subjects. Present outcomes support the study of sleep cycle periods and frequencies in those psychiatric disorders where REM sleep latencies have been found to be shorter, and they suggest that these variables be included in sleep studies in which cycles are compared with each other.

  18. A study on fear memory retrieval and REM sleep in maternal separation and isolation stressed rats.

    PubMed

    Sampath, Dayalan; Sabitha, K R; Hegde, Preethi; Jayakrishnan, H R; Kutty, Bindu M; Chattarji, Sumantra; Rangarajan, Govindan; Laxmi, T R

    2014-10-15

    As rapid brain development occurs during the neonatal period, environmental manipulation during this period may have a significant impact on sleep and memory functions. Moreover, rapid eye movement (REM) sleep plays an important role in integrating new information with the previously stored emotional experience. Hence, the impact of early maternal separation and isolation stress (MS) during the stress hyporesponsive period (SHRP) on fear memory retention and sleep in rats were studied. The neonatal rats were subjected to maternal separation and isolation stress during postnatal days 5-7 (6h daily/3d). Polysomnographic recordings and differential fear conditioning was carried out in two different sets of rats aged 2 months. The neuronal replay during REM sleep was analyzed using different parameters. MS rats showed increased time in REM stage and total sleep period also increased. MS rats showed fear generalization with increased fear memory retention than normal control (NC). The detailed analysis of the local field potentials across different time periods of REM sleep showed increased theta oscillations in the hippocampus, amygdala and cortical circuits. Our findings suggest that stress during SHRP has sensitized the hippocampus-amygdala-cortical loops which could be due to increased release of corticosterone that generally occurs during REM sleep. These rats when subjected to fear conditioning exhibit increased fear memory and increased fear generalization. The development of helplessness, anxiety and sleep changes in human patients, thus, could be related to the reduced thermal, tactile and social stimulation during SHRP on brain plasticity and fear memory functions.

  19. Central Apneas and REM Sleep Behavior Disorder as an Initial Presentation of Multiple System Atrophy

    PubMed Central

    Garcia-Sanchez, Aldara; Fernandez-Navarro, Isabel; Garcia-Rio, Francisco

    2016-01-01

    We present the case of a patient with multiple system atrophy who presented with central apnea as the only sleep disordered breathing, associated with REM behavior disorder and restless legs syndrome. This presentation of the disease is unusual and probably reflects more widespread involvement at the onset. With this case, we show the importance of considering this kind of disease in the differential diagnosis of central sleep apnea syndromes. Citation: Garcia-Sanchez A, Fernandez-Navarro I, Garcia-Rio F. Central apneas and REM sleep behavior disorder as an initial presentation of multiple system atrophy. J Clin Sleep Med 2016;12(2):267–270. PMID:26518702

  20. Purpose of REM sleep: endogenous anti-epileptogenesis in man -- a hypothesis.

    PubMed

    Jaseja, Harinder

    2004-01-01

    Neuro-scientists, worldwide, are endeavoring to elucidate the purpose of sleep which still remains largely elusive. There is, however, consensus on many aspects of sleep functions; one such aspect is its relationship with seizures/epilepsy. There is unequivocal agreement on increased susceptibility to epilepsy during nonrapid eye movement (NREM, slow-wave) sleep. Large number of studies have shown increased frequency of seizures and interictal epileptiform discharges in epileptic patients during NREM sleep (esp., stages I and II) which is associated with EEG synchronization. Similarly, there is widespread acceptance of de-synchronized brain-activity states being associated with rarity/total absence of epileptic potentials, one such state being rapid eye movement (REM) sleep. Certain drugs and substances which inhibit NREM sleep have been found to possess anti-convulsant properties. Not surprisingly, drugs/chemicals which enhance/promote NREM sleep or suppress/inhibit REM sleep are associated with increased susceptibility to seizures and are contraindicated in epilepsy. The manner and pattern in which REM phase occurs in sleep are also naturally programmed to exert anti-epileptogenic influence. This hypothesis-article highlights and conceptualizes the primary function of REM-sleep as endogenous anti-epileptogenic system in the body akin to the endogenous analgesia and immune systems man is born with. PMID:15050104

  1. H-reflex suppression and autonomic activation during lucid REM sleep: a case study.

    PubMed

    Brylowski, A; Levitan, L; LaBerge, S

    1989-08-01

    A single subject, a proficient lucid dreamer experienced with signaling the onset of lucidity (reflective consciousness of dreaming) by means of voluntary eye movements, spent 4 nonconsecutive nights in the sleep laboratory. The subject reported becoming lucid and signaling in 8 of the 18 rapid-eye movement (REM) periods recorded. Ten lucid dream reports were verified by polygraphic examination of signals, providing a total of 12.5 min of signal-verified lucid REM. H-Reflex amplitude was recorded every 5 s, along with continuous recording of electroencephalogram, electrooculogram, electromyogram, electrocardiogram, finger pulse, and respiration. Significant findings included greater mean H-reflex suppression during lucid REM sleep than during nonlucid REM and correlations of H-reflex suppression with increased eye movement density, heart rate, and respiration rate. These results support previous studies reporting that lucid REM is not, as might be supposed, a state closer to awakening than ordinary, or nonlucid, REM; rather, lucid dreaming occurs during unequivocal REM sleep and is characteristically associated with phasic REM activation. PMID:2762692

  2. H-reflex suppression and autonomic activation during lucid REM sleep: a case study.

    PubMed

    Brylowski, A; Levitan, L; LaBerge, S

    1989-08-01

    A single subject, a proficient lucid dreamer experienced with signaling the onset of lucidity (reflective consciousness of dreaming) by means of voluntary eye movements, spent 4 nonconsecutive nights in the sleep laboratory. The subject reported becoming lucid and signaling in 8 of the 18 rapid-eye movement (REM) periods recorded. Ten lucid dream reports were verified by polygraphic examination of signals, providing a total of 12.5 min of signal-verified lucid REM. H-Reflex amplitude was recorded every 5 s, along with continuous recording of electroencephalogram, electrooculogram, electromyogram, electrocardiogram, finger pulse, and respiration. Significant findings included greater mean H-reflex suppression during lucid REM sleep than during nonlucid REM and correlations of H-reflex suppression with increased eye movement density, heart rate, and respiration rate. These results support previous studies reporting that lucid REM is not, as might be supposed, a state closer to awakening than ordinary, or nonlucid, REM; rather, lucid dreaming occurs during unequivocal REM sleep and is characteristically associated with phasic REM activation.

  3. Coherent neocortical gamma oscillations decrease during REM sleep in the rat.

    PubMed

    Cavelli, Matías; Castro, Santiago; Schwarzkopf, Natalia; Chase, Michael H; Falconi, Atilio; Torterolo, Pablo

    2015-03-15

    Higher cognitive functions require the integration and coordination of large populations of neurons in cortical and subcortical regions. Oscillations in the high frequency band (30-100 Hz) of the electroencephalogram (EEG), that have been postulated to be a product of this interaction, are involved in the binding of spatially separated but temporally correlated neural events, which results in a unified perceptual experience. The extent of this functional connectivity can be examined by means of the mathematical algorithm called "coherence", which is correlated with the "strength" of functional interactions between cortical areas. As a continuation of previous studies in the cat [6,7], the present study was conducted to analyze EEG coherence in the gamma band of the rat during wakefulness (W), non-REM (NREM) sleep and REM sleep. Rats were implanted with electrodes in different cortical areas to record EEG activity, and the magnitude squared coherence values within the gamma frequency band of EEG (30-48 and 52-100 Hz) were determined. Coherence between all cortical regions in the low and high gamma frequency bands was greater during W compared with sleep. Remarkably, EEG coherence in the low and high gamma bands was smallest during REM sleep. We conclude that high frequency interactions between cortical areas are radically different during sleep and wakefulness in the rat. Since this feature is conserved in other mammals, including humans, we suggest that the uncoupling of gamma frequency activity during REM sleep is a defining trait of REM sleep in mammals. PMID:25557796

  4. The role of REM sleep in the processing of emotional memories: evidence from behavior and event-related potentials.

    PubMed

    Groch, S; Wilhelm, I; Diekelmann, S; Born, J

    2013-01-01

    Emotional memories are vividly remembered for the long-term. Rapid eye movement (REM) sleep has been repeatedly proposed to support the superior retention of emotional memories. However, its exact contribution and, specifically, whether its effect is mainly on the consolidation of the contents or the processing of the affective component of emotional memories is not clear. Here, we investigated the effects of sleep rich in slow wave sleep (SWS) or REM sleep on the consolidation of emotional pictures and the accompanying changes in affective tone, using event-related potentials (ERPs) together with subjective ratings of valence and arousal. Sixteen healthy, young men learned 50 negative and 50 neutral pictures before 3-h retention sleep intervals that were filled with either SWS-rich early or REM sleep-rich late nocturnal sleep. In accordance with our hypothesis, recognition was better for emotional pictures than neutral pictures after REM compared to SWS-rich sleep. This emotional enhancement after REM-rich sleep expressed itself in an increased late positive potential of the ERP over the frontal cortex 300-500 ms after stimulus onset for correctly classified old emotional pictures compared with new emotional and neutral pictures. Valence and arousal ratings of emotional pictures were not differentially affected by REM or SWS-rich sleep after learning. Our results corroborate that REM sleep contributes to the consolidation of emotional contents in memory, but suggest that the affective tone is preserved rather than reduced by the processing of emotional memories during REM sleep.

  5. Semantic priming effect during REM-sleep inertia in patients with narcolepsy.

    PubMed

    Mazzetti, Michela; Campi, Claudio; Mattarozzi, Katia; Plazzi, Giuseppe; Tuozzi, Giovanni; Vandi, Stefano; Vignatelli, Luca; Cipolli, Carlo

    2006-12-11

    Patients with narcolepsy-cataplexy (NC) present excessive daytime sleepiness (EDS), cataplexy and an altered architecture of nocturnal sleep, with frequent episodes of REM-sleep at sleep onset (SOREM-sleep). This altered organization of nocturnal sleep may be accompanied by some differences in the functioning of the cognitive processes involved in the access, organization and consolidation of information during sleep. This study attempts to ascertain whether the activation of semantic memory during REM-sleep, as measured using a technique of semantic priming (namely, the facilitation of the activation of strongly-related rather than weakly-related and, overall, unrelated pairs of prime-target words) is different in NC patients compared to normal subjects. A lexical decision task (LDT) was carried out twice in wakefulness (at 10a.m. and after a 24h interval) and twice in the period of sleep inertia following awakening from SOREM and 4th-cycle REM-sleep on 12 NC patients and from 1st- and 4th-cycle REM-sleep on 12 matched controls. Reaction time (RT) to target words, taken as a measure of the semantic priming effect, proved to be longer (a) in NC patients than in control subjects; (b) in the period of REM-sleep inertia than in wakefulness; (c) in the first rather than the second session; and (d) for unrelated compared to weakly-related and, overall, strongly-related prime-target pairs. RT in post-REM-sleep sessions was less impaired, compared to waking sessions, and less dependent on the associative strength of prime-target pairs in NC patients than in normal subjects. Finally, RT of NC patients, although longer than that of normal subjects in waking sessions, significantly improved in the second session, as a consequence of either the amount of exercise or the consolidation advantage provided by REM-sleep for the procedural components of the task. The whole picture suggests a greater effectiveness of the activation of semantic memory during (SO)REM-sleep in NC

  6. Estradiol modulates recovery of REM sleep in a time-of-day-dependent manner.

    PubMed

    Schwartz, Michael D; Mong, Jessica A

    2013-08-01

    Ovarian hormones are thought to modulate sleep and fluctuations in the hormonal milieu are coincident with sleep complaints in women. In female rats, estradiol increases waking and suppresses sleep. In this study, we asked whether this effect is mediated via circadian or homeostatic regulatory mechanisms. Ovariectomized female rats received daily injections of estradiol benzoate (EB) or sesame oil that mimicked the rapid increase and subsequent decline of circulating estradiol at proestrus. In one experiment, animals were sleep deprived for 6 h starting at lights-on, so that recovery began in the mid-light phase; in the second experiment, animals were sleep deprived starting in the mid-light phase, so that recovery began at lights-off. EB suppressed baseline rapid eye movement (REM) and non-REM (NREM) sleep and increased waking in the dark phase. In both experiments, EB enhanced REM recovery in the light phase while suppressing it in the dark compared with oil; this effect was most pronounced in the first 6 h of recovery. By contrast, NREM recovery was largely unaffected by EB. In summary, EB enhanced waking and suppressed sleep, particularly REM sleep, in the dark under baseline and recovery conditions. These strong temporally dependent effects suggest that EB consolidates circadian sleep-wake rhythms in female rats.

  7. Motivation and affect in REM sleep and the mentation reporting process.

    PubMed

    Smith, Mark R; Antrobus, John S; Gordon, Evelyn; Tucker, Matthew A; Hirota, Yasutaka; Wamsley, Erin J; Ross, Lars; Doan, Tieu; Chaklader, Annie; Emery, Rebecca N

    2004-09-01

    Although the emotional and motivational characteristics of dreaming have figured prominently in folk and psychoanalytic conceptions of dream production, emotions have rarely been systematically studied, and motivation, never. Because emotions during sleep lack the somatic components of waking emotions, and they change as the sleeper awakens, their properties are difficult to assess. Recent evidence of limbic system activation during REM sleep suggests a basis in brain architecture for the interaction of motivational and cognitive properties in dreaming. Motivational and emotional content in REM and NREM laboratory mentation reports from 25 participants were compared. Motivational and emotional content was significantly greater in REM than NREM sleep, even after controlling for the greater word count of REM reports.

  8. Single-neuron activity and eye movements during human REM sleep and awake vision

    PubMed Central

    Andrillon, Thomas; Nir, Yuval; Cirelli, Chiara; Tononi, Giulio; Fried, Itzhak

    2015-01-01

    Are rapid eye movements (REMs) in sleep associated with visual-like activity, as during wakefulness? Here we examine single-unit activities (n=2,057) and intracranial electroencephalography across the human medial temporal lobe (MTL) and neocortex during sleep and wakefulness, and during visual stimulation with fixation. During sleep and wakefulness, REM onsets are associated with distinct intracranial potentials, reminiscent of ponto-geniculate-occipital waves. Individual neurons, especially in the MTL, exhibit reduced firing rates before REMs as well as transient increases in firing rate immediately after, similar to activity patterns observed upon image presentation during fixation without eye movements. Moreover, the selectivity of individual units is correlated with their response latency, such that units activated after a small number of images or REMs exhibit delayed increases in firing rates. Finally, the phase of theta oscillations is similarly reset following REMs in sleep and wakefulness, and after controlled visual stimulation. Our results suggest that REMs during sleep rearrange discrete epochs of visual-like processing as during wakefulness. PMID:26262924

  9. Locus Coeruleus and Tuberomammillary Nuclei Ablations Attenuate Hypocretin/Orexin Antagonist-Mediated REM Sleep.

    PubMed

    Schwartz, Michael D; Nguyen, Alexander T; Warrier, Deepti R; Palmerston, Jeremiah B; Thomas, Alexia M; Morairty, Stephen R; Neylan, Thomas C; Kilduff, Thomas S

    2016-01-01

    Hypocretin 1 and 2 (Hcrts; also known as orexin A and B), excitatory neuropeptides synthesized in cells located in the tuberal hypothalamus, play a central role in the control of arousal. Hcrt inputs to the locus coeruleus norepinephrine (LC NE) system and the posterior hypothalamic histaminergic tuberomammillary nuclei (TMN HA) are important efferent pathways for Hcrt-induced wakefulness. The LC expresses Hcrt receptor 1 (HcrtR1), whereas HcrtR2 is found in the TMN. Although the dual Hcrt/orexin receptor antagonist almorexant (ALM) decreases wakefulness and increases NREM and REM sleep time, the neural circuitry that mediates these effects is currently unknown. To test the hypothesis that ALM induces sleep by selectively disfacilitating subcortical wake-promoting populations, we ablated LC NE neurons (LCx) or TMN HA neurons (TMNx) in rats using cell-type-specific saporin conjugates and evaluated sleep/wake following treatment with ALM and the GABAA receptor modulator zolpidem (ZOL). Both LCx and TMNx attenuated the promotion of REM sleep by ALM without affecting ALM-mediated increases in NREM sleep. Thus, eliminating either HcrtR1 signaling in the LC or HcrtR2 signaling in the TMN yields similar effects on ALM-induced REM sleep without affecting NREM sleep time. In contrast, neither lesion altered ZOL efficacy on any measure of sleep-wake regulation. These results contrast with those of a previous study in which ablation of basal forebrain cholinergic neurons attenuated ALM-induced increases in NREM sleep time without affecting REM sleep, indicating that Hcrt neurotransmission influences distinct aspects of NREM and REM sleep at different locations in the sleep-wake regulatory network.

  10. The homeostatic regulation of REM sleep: A role for localized expression of brain-derived neurotrophic factor in the brainstem.

    PubMed

    Datta, Subimal; Knapp, Clifford M; Koul-Tiwari, Richa; Barnes, Abigail

    2015-10-01

    Homeostatic regulation of REM sleep plays a key role in neural plasticity and deficits in this process are implicated in the development of many neuropsychiatric disorders. Little is known, however, about the molecular mechanisms that underlie this homeostatic regulation process. This study examined the hypothesis that, during selective REM sleep deprivation (RSD), increased brain-derived neurotrophic factor (BDNF) expression in REM sleep regulating areas is critical for the development of homeostatic drive for REM sleep, as measured by an increase in the number of REM sleep transitions. Rats were assigned to RSD, non-sleep deprived (BSL), or total sleep deprivation (TSD) groups. Physiological recordings were obtained from cortical, hippocampal, and pontine EEG electrodes over a 6h period, in which sleep deprivation occurred during the first 3h. In the RSD, but not the other conditions, homeostatic drive for REM sleep increased progressively. BDNF protein expression was significantly greater in the pedunculopontine tegmentum (PPT) and subcoeruleus nucleus (SubCD) in the RSD as compared to the TSD and BSL groups, areas that regulate REM sleep, but not in the medial preoptic area, which regulates non-REM sleep. There was a significant positive correlation between RSD-induced increases in number of REM sleep episodes and increased BDNF expression in the PPT and SubCD. These increases positively correlated with levels of homeostatic drive for REM sleep. These results, for the first time, suggest that selective RSD-induced increased expression of BDNF in the PPT and SubCD are determinant factors in the development of the homeostatic drive for REM sleep.

  11. A parasomnia overlap disorder involving sleepwalking, sleep terrors, and REM sleep behavior disorder in 33 polysomnographically confirmed cases.

    PubMed

    Schenck, C H; Boyd, J L; Mahowald, M W

    1997-11-01

    A series of 33 patients with combined (injurious) sleepwalking, sleep terrors, and rapid eye movement (REM) sleep behavior disorder (viz. "parasomnia overlap disorder") was gathered over an 8-year period. Patients underwent clinical and polysomnographic evaluations. Mean age was 34 +/- 14 (SD) years; mean age of parasomnia onset was 15 +/- 16 years (range 1-66); 70% (n = 23) were males. An idiopathic subgroup (n = 22) had a significantly earlier mean age of parasomnia onset (9 +/- 7 years) than a symptomatic subgroup (n = 11) (27 +/- 23 years, p = 0.002), whose parasomnia began with either of the following: neurologic disorders, n = 6 [congenital Mobius syndrome, narcolepsy, multiple sclerosis, brain tumor (and treatment), brain trauma, indeterminate disorder (exaggerated startle response/atypical cataplexy)]; nocturnal paroxysmal atrial fibrillation, n = 1; posttraumatic stress disorder/major depression, n = 1; chronic ethanol/amphetamine abuse and withdrawal, n = 1; or mixed disorders (schizophrenia, brain trauma, substance abuse), n = 2. The rate of DSM-III-R (Diagnostic and Statistical Manual, 3rd edition, revised) Axis 1 psychiatric disorders was not elevated; group scores on various psychometric tests were not elevated. Forty-five percent (n = 15) had previously received psychologic or psychiatric therapy for their parasomnia, without benefit. Treatment outcome was available for n = 20 patients; 90% (n = 18) had substantial parasomnia control with bedtime clonazepam (n = 13), alprazolam and/or carbamazepine (n = 4), or self-hypnosis (n = 1). Thus, "parasomnia overlap disorder" is a treatable condition that emerges in various clinical settings and can be understood within the context of current knowledge on parasomnias and motor control/dyscontrol during sleep. PMID:9456462

  12. Replay of conditioned stimuli during late REM and stage N2 sleep influences affective tone rather than emotional memory strength.

    PubMed

    Rihm, Julia S; Rasch, Björn

    2015-07-01

    Emotional memories are reprocessed during sleep, and it is widely assumed that this reprocessing occurs mainly during rapid eye movement (REM) sleep. In support for this notion, vivid emotional dreams occur mainly during REM sleep, and several studies have reported emotional memory enhancement to be associated with REM sleep or REM sleep-related parameters. However, it is still unknown whether reactivation of emotional memories during REM sleep strengthens emotional memories. Here, we tested whether re-presentation of emotionally learned stimuli during REM sleep enhances emotional memory. In a split-night design, participants underwent Pavlovian conditioning after the first half of the night. Neutral sounds served as conditioned stimuli (CS) and were either paired with a negative odor (CS+) or an odorless vehicle (CS-). During sound replay in subsequent late REM or N2 sleep, half of the CS+ and half of the CS- were presented again. In contrast to our hypothesis, replay during sleep did not affect emotional memory as measured by the differentiation between CS+ and CS- in expectancy, arousal and valence ratings. However, replay unspecifically decreased subjective arousal ratings of both emotional and neutral sounds and increased positive valence ratings also for both CS+ and CS- sounds, respectively. These effects were slightly more pronounced for replay during REM sleep. Our results suggest that re-exposure to previously conditioned stimuli during late sleep does not affect emotional memory strength, but rather influences the affective tone of both emotional and neutral memories. PMID:25933506

  13. Replay of conditioned stimuli during late REM and stage N2 sleep influences affective tone rather than emotional memory strength.

    PubMed

    Rihm, Julia S; Rasch, Björn

    2015-07-01

    Emotional memories are reprocessed during sleep, and it is widely assumed that this reprocessing occurs mainly during rapid eye movement (REM) sleep. In support for this notion, vivid emotional dreams occur mainly during REM sleep, and several studies have reported emotional memory enhancement to be associated with REM sleep or REM sleep-related parameters. However, it is still unknown whether reactivation of emotional memories during REM sleep strengthens emotional memories. Here, we tested whether re-presentation of emotionally learned stimuli during REM sleep enhances emotional memory. In a split-night design, participants underwent Pavlovian conditioning after the first half of the night. Neutral sounds served as conditioned stimuli (CS) and were either paired with a negative odor (CS+) or an odorless vehicle (CS-). During sound replay in subsequent late REM or N2 sleep, half of the CS+ and half of the CS- were presented again. In contrast to our hypothesis, replay during sleep did not affect emotional memory as measured by the differentiation between CS+ and CS- in expectancy, arousal and valence ratings. However, replay unspecifically decreased subjective arousal ratings of both emotional and neutral sounds and increased positive valence ratings also for both CS+ and CS- sounds, respectively. These effects were slightly more pronounced for replay during REM sleep. Our results suggest that re-exposure to previously conditioned stimuli during late sleep does not affect emotional memory strength, but rather influences the affective tone of both emotional and neutral memories.

  14. REM Sleep Behavior Disorder: Updated Review of the Core Features, the RBD-Neurodegenerative Disease Association, Evolving Concepts, Controversies, and Future Directions

    PubMed Central

    Boeve, Bradley F.

    2010-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. Patients appear to “act out their dreams,” in which the exhibited behaviors mirror the content of the dreams, and the dream content often involves a chasing or attacking theme. The polysomnographic features of RBD include increased electromyographic tone +/- dream enactment behavior during REM sleep. Management with counseling and pharmacologic measures is usually straight-forward and effective. In this review, the terminology, clinical and polysomnographic features, demographic and epidemiologic features, diagnostic criteria, differential diagnosis, and management strategies are discussed. Recent data on the suspected pathophysiologic mechanisms of RBD are also reviewed. The literature and our institutional experience on RBD are next discussed, with an emphasis on the RBD-neurodegenerative disease association and particularly the RBD-synucleinopathy association. Several issues relating to evolving concepts, controversies, and future directions are then reviewed, with an emphasis on idiopathic RBD representing an early feature of a neurodegenerative disease and particularly an evolving synucleinopathy. Planning for future therapies that impact patients with idiopathic RBD is reviewed in detail. PMID:20146689

  15. Why Does Rem Sleep Occur? A Wake-Up Hypothesis1

    PubMed Central

    Klemm, W. R.

    2011-01-01

    Brain activity differs in the various sleep stages and in conscious wakefulness. Awakening from sleep requires restoration of the complex nerve impulse patterns in neuronal network assemblies necessary to re-create and sustain conscious wakefulness. Herein I propose that the brain uses rapid eye movement (REM) to help wake itself up after it has had a sufficient amount of sleep. Evidence suggesting this hypothesis includes the facts that, (1) when first going to sleep, the brain plunges into Stage N3 (formerly called Stage IV), a deep abyss of sleep, and, as the night progresses, the sleep is punctuated by episodes of REM that become longer and more frequent toward morning, (2) conscious-like dreams are a reliable component of the REM state in which the dreamer is an active mental observer or agent in the dream, (3) the last awakening during a night's sleep usually occurs in a REM episode during or at the end of a dream, (4) both REM and awake consciousness seem to arise out of a similar brainstem ascending arousal system (5) N3 is a functionally perturbed state that eventually must be corrected so that embodied brain can direct adaptive behavior, and (6) cortico-fugal projections to brainstem arousal areas provide a way to trigger increased cortical activity in REM to progressively raise the sleeping brain to the threshold required for wakefulness. This paper shows how the hypothesis conforms to common experience and has substantial predictive and explanatory power regarding the phenomenology of sleep in terms of ontogeny, aging, phylogeny, abnormal/disease states, cognition, and behavioral physiology. That broad range of consistency is not matched by competing theories, which are summarized herein. Specific ways to test this wake-up hypothesis are suggested. Such research could lead to a better understanding of awake consciousness. PMID:21922003

  16. Tonic inhibition and ponto-geniculo-occipital-related activities shape abducens motoneuron discharge during REM sleep.

    PubMed

    Escudero, Miguel; Márquez-Ruiz, Javier

    2008-07-15

    Eye movements, ponto-geniculo-occipital (PGO) waves, muscular atonia and desynchronized cortical activity are the main characteristics of rapid eye movement (REM) sleep. Although eye movements designate this phase, little is known about the activity of the oculomotor system during REM sleep. In this work, we recorded binocular eye movements by the scleral search-coil technique and the activity of identified abducens (ABD) motoneurons along the sleep-wake cycle in behaving cats. The activity of ABD motoneurons during REM sleep was characterized by a tonic decrease of their mean firing rate throughout this period, and short bursts and pauses coinciding with the occurrence of PGO waves. We demonstrate that the decrease in the mean firing discharge was due to an active inhibition of ABD motoneurons, and that the occurrence of primary and secondary PGO waves induced a pattern of simultaneous but opposed phasic activation and inhibition on each ABD nucleus. With regard to eye movements, during REM sleep ABD motoneurons failed to codify eye position as during alertness, but continued to codify eye velocity. The pattern of tonic inhibition and the phasic activations and inhibitions shown by ABD motoneurons coincide with those reported in other non-oculomotor motoneurons, indicating that the oculomotor system - contrary to what has been accepted until now - is not different from other motor systems during REM sleep, and that all motor systems are receiving similar command signals during this period.

  17. REM sleep deprivation in rats results in inflammation and interleukin-17 elevation.

    PubMed

    Yehuda, Shlomo; Sredni, Benjamin; Carasso, Rafi L; Kenigsbuch-Sredni, Dvora

    2009-07-01

    Sleep deprivation is a major health problem in modern society. Deprivation of rapid eye movement (REM) sleep is particularly damaging to cognition and to spatial memory; however, the mechanisms that mediate these deteriorations in function are not known. We explored the possibility that REM sleep deprivation may provoke major changes in the immune system by inducing inflammation. Rats were subjected to 72 h of REM sleep deprivation, and the plasma levels of proinflammatory cytokines (IL-1, IL-1beta, IL-6, IL-17A, and TNF-alpha), an anti-inflammatory cytokine (IL-10), the inflammatory markers homocysteine, corticosterone, and hyperthermia were measured immediately after the deprivation period, and 7 days later. The results indicate that REM sleep deprivation induced an inflammatory response. The levels of the proinflammatory cytokines and markers were significantly elevated in sleep-deprived rats as compared to control rats. After 7 days of recovery, the levels of some markers, including hyperthermia, remained higher in sleep-deprived rats versus the control animals. IL-17A appears to play a pivotal role in coordinating the inflammation. These data shed new light on the mechanism of sleep deprivation-induced inflammation.

  18. The Memory Function of Noradrenergic Activity in Non-REM Sleep

    ERIC Educational Resources Information Center

    Gais, Steffen; Rasch, Bjorn; Dahmen, Johannes C.; Sara, Susan; Born, Jan

    2011-01-01

    There is a long-standing assumption that low noradrenergic activity during sleep reflects mainly the low arousal during this brain state. Nevertheless, recent research has demonstrated that the locus coeruleus, which is the main source of cortical noradrenaline, displays discrete periods of intense firing during non-REM sleep, without any signs of…

  19. Is a purpose of REM sleep atonia to help regenerate intervertebral disc volumetric loss?

    PubMed Central

    Fryer, Jerome CJ

    2009-01-01

    The nature of atonia in sleep continues to be enigmatic. This article discusses a new hypothesis for complete core muscle relaxation in REM sleep, suggesting a bottom-up recuperative perspective. That is, does the atonia in REM sleep provide a utility to help restore the mechanobiology and respective diurnal intervertebral disc hydraulic loss? By combining the effects of gravity with current compressive concepts in spinal stability, this article looks at vertebral approximation as a deleterious experience with an intrinsic biological need to keep vertebrae separated. Methods using polysomnography and recumbent MRI are discussed. PMID:19123938

  20. REM sleep deprivation of rats induces acute phase response in liver.

    PubMed

    Pandey, Atul Kumar; Kar, Santosh Kumar

    2011-07-01

    REM sleep is essential for maintenance of body physiology and its deprivation is fatal. We observed that the levels of ALT and AST enzymes and pro-inflammatory cytokines like IL-1 β, IL-6 and IL-12 circulating in the blood of REM sleep deprived rats increased in proportion to the extent of sleep loss. But in contrast the levels of IFN-γ and a ∼200 kDa protein, identified by N-terminal sequencing to be alpha-1-inhibitor-3(A1I3), decreased significantly. Quantitative PCR analysis confirmed that REM sleep deprivation down regulates AII3 gene and up regulates IL1 β, IL6 and their respective receptors gene expression in the liver initiating its inflammation.

  1. Oximetry Signal Processing Identifies REM Sleep-Related Vulnerability Trait in Asthmatic Children

    PubMed Central

    Perez, Geovanny F.; Gutierrez, Maria J.; Huseni, Shehlanoor; Pancham, Khrisna; Rodriguez-Martinez, Carlos E.; Nino, Cesar L.; Nino, Gustavo

    2013-01-01

    Rationale. The sleep-related factors that modulate the nocturnal worsening of asthma in children are poorly understood. This study addressed the hypothesis that asthmatic children have a REM sleep-related vulnerability trait that is independent of OSA. Methods. We conducted a retrospective cross-sectional analysis of pulse-oximetry signals obtained during REM and NREM sleep in control and asthmatic children (n = 134). Asthma classification was based on preestablished clinical criteria. Multivariate linear regression model was built to control for potential confounders (significance level P ≤ 0.05). Results. Our data demonstrated that (1) baseline nocturnal respiratory parameters were not significantly different in asthmatic versus control children, (2) the maximal % of SaO2 desaturation during REM, but not during NREM, was significantly higher in asthmatic children, and (3) multivariate analysis revealed that the association between asthma and REM-related maximal % SaO2 desaturation was independent of demographic variables. Conclusion. These results demonstrate that children with asthma have a REM-related vulnerability trait that impacts oxygenation independently of OSA. Further research is needed to delineate the REM sleep neurobiological mechanisms that modulate the phenotypical expression of nocturnal asthma in children. PMID:24288619

  2. The predictive value of Muller maneuver in REM-dependent obstructive sleep apnea.

    PubMed

    Ozcan, Kursat Murat; Ozcan, Muge; Ozdogan, Fatih; Hizli, Omer; Dere, Huseyin; Unal, Adnan

    2013-09-01

    To our knowledge, no studies up to date have investigated the correlation of rapid eye movement (REM) dependent obstructive sleep apnea syndrome (OSAS) and Muller maneuver. The aim of this study is to investigate whether REM-dependent OSAS is predicted by the findings of the Muller maneuver. The study was conducted on 149 patients with witnessed apnea and daytime sleepiness. Muller maneuver was performed to all patients and the obstruction site was determined using a five-point scale. Then, polysomnography of the patient was obtained and the apnea-hypopnea indexes were determined in total sleep time, REM-dependent sleep and non-REM-dependent sleep. The correlations between the Muller maneuver findings and polysomnographic data were analyzed. The ages of the patients included in the study ranged between 25 and 73 years with a mean age of 49.3 ± 10.1 years. Their mean body mass index was 30.8 ± 5.1 kg/m(2) (range 21.9-55.4 kg/m(2)). The patients' mean apnea-hypopnea indexes in total sleep time was 28.1 and ranged between 5.4 and 124.3. REM-dependent OSAS was determined in 49 patients. When the data were analyzed, it was determined that there were no statistically significant correlations between tongue base or lateral pharyngeal band obstruction at the level of hypopharynx and the REM-dependent OSAS. At the level of the soft palate, the obstruction caused by the lateral pharyngeal bands or soft palate and REM dependency did not show any statistically significant correlation (p > 0.05). In conclusion, Muller maneuver does not provide useful data to predict REM dependency of OSAS.

  3. From REM sleep behaviour disorder to status dissociatus: insights into the maze of states of being.

    PubMed

    Vetrugno, Roberto; Montagna, Pasquale

    2011-12-01

    Sleep is a coordinated process involving more or less simultaneous changes in sensory, motor, autonomic, hormonal, and cerebral processes. On the other hand, none of the changes occurring with sleep are invariably coupled to sleep. EEG synchrony, heat loss, sleep-related hormone secretion, and even REM-related motoneuron paralysis may occur independent of the parent state. In REM sleep behaviour disorder (RBD) the muscle tone of wakefulness intrudes into REM sleep, allowing the release of dream-enacting behaviours. Status dissociatus (SD) is a condition in which brain and mind are in disarray along the boundaries of sleep and wakefulness. The existence of such dissociated behaviours shows that they have separate neuronal control systems and indicates that the whole organization of sleep is an emergent property of the collective neuronal systems to synchronize. Insults to the brain can drastically alter the circuitries responsible for maintaining the integrity of wakefulness, NREM sleep, and REM sleep. As a consequence, the basic states of existence can become admixed and interchanged with striking disturbances of consciousness, brain electrophysiology, and the behavioural and polygraphic expression of sleep and wakefulness. The evolution of RBD into SD may result from a disarray of (brainstem) structures that orchestrate the whole brain wake-sleep conditions, but with preserved discrete systems and dissociable strategies to still place navigation in wake and sleep. Advances in the fields of genetics, neuroimaging, and behavioural neurology will expand the understanding of the mechanisms underlying the organization of the states of being along with their somatic/behavioural manifestations.

  4. The H1 histamine receptor blocker, chlorpheniramine, completely prevents the increase in REM sleep induced by immobilization stress in rats.

    PubMed

    Rojas-Zamorano, J A; Esqueda-Leon, E; Jimenez-Anguiano, A; Cintra-McGlone, L; Mendoza Melendez, M A; Velazquez Moctezuma, J

    2009-01-01

    Chlorpheniramine is a selective antagonist of the H1 histaminergic receptor subtype and its effects in humans include somnolence. Chlorpheniramine affects sleep in rats, mainly by decreasing REM sleep. On the other hand, stress by immobilization induces an important increase in the percentage of REM sleep. In this study we analyzed the effects of blocking histaminergic receptors on REM sleep induced by immobilization stress. Adult male Wistar rats were chronically implanted for sleep recording. Immobilization stress was induced by placing the rat in a small cylinder for 2 h. Experimental conditions were: A. Control; B. Stress; C. Stress plus vehicle and D. Stress plus chlorpheniramine. Independent experiments were done both in the dark, as well as the light period. Results showed that the increase in REM sleep observed after immobilization stress was completely abolished by chlorpheniramine, both in the dark and in the light phase. Furthermore, the decrease in REM sleep was significant even when compared to the non-stressed control rats. REM sleep latency was also significantly longer during both light phases. The present results suggest that REM sleep is quite sensitive to histaminergic blockage. It is possible that chlorpheniramine is also blocking the cholinergic mechanisms generating REM sleep.

  5. The effect of selective REM-sleep deprivation on the consolidation and affective evaluation of emotional memories.

    PubMed

    Wiesner, Christian D; Pulst, Julika; Krause, Fanny; Elsner, Marike; Baving, Lioba; Pedersen, Anya; Prehn-Kristensen, Alexander; Göder, Robert

    2015-07-01

    Emotion boosts the consolidation of events in the declarative memory system. Rapid eye movement (REM) sleep is believed to foster the memory consolidation of emotional events. On the other hand, REM sleep is assumed to reduce the emotional tone of the memory. Here, we investigated the effect of selective REM-sleep deprivation, SWS deprivation, or wake on the affective evaluation and consolidation of emotional and neutral pictures. Prior to an 9-h retention interval, sixty-two healthy participants (23.5 ± 2.5 years, 32 female, 30 male) learned and rated their affect to 80 neutral and 80 emotionally negative pictures. Despite rigorous deprivation of REM sleep or SWS, the residual sleep fostered the consolidation of neutral and negative pictures. Furthermore, emotional arousal helped to memorize the pictures. The better consolidation of negative pictures compared to neutral ones was most pronounced in the SWS-deprived group where a normal amount of REM sleep was present. This emotional memory bias correlated with REM sleep only in the SWS-deprived group. Furthermore, emotional arousal to the pictures decreased over time, but neither sleep nor wake had any differential effect. Neither the comparison of the affective ratings (arousal, valence) during encoding and recognition, nor the affective ratings of the recognized targets and rejected distractors supported the hypothesis that REM sleep dampens the emotional reaction to remembered stimuli. The data suggest that REM sleep fosters the consolidation of emotional memories but has no effect on the affective evaluation of the remembered contents. PMID:25708092

  6. The effect of selective REM-sleep deprivation on the consolidation and affective evaluation of emotional memories.

    PubMed

    Wiesner, Christian D; Pulst, Julika; Krause, Fanny; Elsner, Marike; Baving, Lioba; Pedersen, Anya; Prehn-Kristensen, Alexander; Göder, Robert

    2015-07-01

    Emotion boosts the consolidation of events in the declarative memory system. Rapid eye movement (REM) sleep is believed to foster the memory consolidation of emotional events. On the other hand, REM sleep is assumed to reduce the emotional tone of the memory. Here, we investigated the effect of selective REM-sleep deprivation, SWS deprivation, or wake on the affective evaluation and consolidation of emotional and neutral pictures. Prior to an 9-h retention interval, sixty-two healthy participants (23.5 ± 2.5 years, 32 female, 30 male) learned and rated their affect to 80 neutral and 80 emotionally negative pictures. Despite rigorous deprivation of REM sleep or SWS, the residual sleep fostered the consolidation of neutral and negative pictures. Furthermore, emotional arousal helped to memorize the pictures. The better consolidation of negative pictures compared to neutral ones was most pronounced in the SWS-deprived group where a normal amount of REM sleep was present. This emotional memory bias correlated with REM sleep only in the SWS-deprived group. Furthermore, emotional arousal to the pictures decreased over time, but neither sleep nor wake had any differential effect. Neither the comparison of the affective ratings (arousal, valence) during encoding and recognition, nor the affective ratings of the recognized targets and rejected distractors supported the hypothesis that REM sleep dampens the emotional reaction to remembered stimuli. The data suggest that REM sleep fosters the consolidation of emotional memories but has no effect on the affective evaluation of the remembered contents.

  7. Locus Coeruleus and Tuberomammillary Nuclei Ablations Attenuate Hypocretin/Orexin Antagonist-Mediated REM Sleep123

    PubMed Central

    Nguyen, Alexander T.; Warrier, Deepti R.; Palmerston, Jeremiah B.; Thomas, Alexia M.; Morairty, Stephen R.; Neylan, Thomas C.

    2016-01-01

    Abstract Hypocretin 1 and 2 (Hcrts; also known as orexin A and B), excitatory neuropeptides synthesized in cells located in the tuberal hypothalamus, play a central role in the control of arousal. Hcrt inputs to the locus coeruleus norepinephrine (LC NE) system and the posterior hypothalamic histaminergic tuberomammillary nuclei (TMN HA) are important efferent pathways for Hcrt-induced wakefulness. The LC expresses Hcrt receptor 1 (HcrtR1), whereas HcrtR2 is found in the TMN. Although the dual Hcrt/orexin receptor antagonist almorexant (ALM) decreases wakefulness and increases NREM and REM sleep time, the neural circuitry that mediates these effects is currently unknown. To test the hypothesis that ALM induces sleep by selectively disfacilitating subcortical wake-promoting populations, we ablated LC NE neurons (LCx) or TMN HA neurons (TMNx) in rats using cell-type-specific saporin conjugates and evaluated sleep/wake following treatment with ALM and the GABAA receptor modulator zolpidem (ZOL). Both LCx and TMNx attenuated the promotion of REM sleep by ALM without affecting ALM-mediated increases in NREM sleep. Thus, eliminating either HcrtR1 signaling in the LC or HcrtR2 signaling in the TMN yields similar effects on ALM-induced REM sleep without affecting NREM sleep time. In contrast, neither lesion altered ZOL efficacy on any measure of sleep–wake regulation. These results contrast with those of a previous study in which ablation of basal forebrain cholinergic neurons attenuated ALM-induced increases in NREM sleep time without affecting REM sleep, indicating that Hcrt neurotransmission influences distinct aspects of NREM and REM sleep at different locations in the sleep–wake regulatory network. PMID:27022631

  8. Coherent neocortical 40-Hz oscillations are not present during REM sleep.

    PubMed

    Castro, Santiago; Falconi, Atilio; Chase, Michael H; Torterolo, Pablo

    2013-04-01

    During cognitive processes there are extensive interactions between various regions of the cerebral cortex. Oscillations in the gamma frequency band (≈40 Hz) of the electroencephalogram (EEG) are involved in the binding of spatially separated but temporally correlated neural events, which results in a unified perceptual experience. The extent of these interactions can be examined by means of a mathematical algorithm called 'coherence', which reflects the 'strength' of functional interactions between cortical areas. The present study was conducted to analyse EEG coherence in the gamma frequency band of the cat during alert wakefulness (AW), quiet wakefulness (QW), non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Cats were implanted with electrodes in the frontal, parietal and occipital cortices to monitor EEG activity. Coherence values within the gamma frequency (30-100 Hz) from pairs of EEG recordings were analysed. A large increase in coherence occurred between all cortical regions in the 30-45 Hz frequency band during AW compared with the other behavioral states. As the animal transitioned from AW to QW and from QW to NREM sleep, coherence decreased to a moderate level. Remarkably, there was practically no EEG coherence in the entire gamma band spectrum (30-100 Hz) during REM sleep. We conclude that functional interactions between cortical areas are radically different during sleep compared with wakefulness. The virtual absence of gamma frequency coherence during REM sleep may underlie the unique cognitive processing that occurs during dreams, which is principally a REM sleep-related phenomenon. PMID:23406153

  9. REM Sleep Enhancement of Probabilistic Classification Learning is Sensitive to Subsequent Interference

    PubMed Central

    Barsky, Murray M.; Tucker, Matthew A.; Stickgold, Robert

    2015-01-01

    During wakefulness the brain creates meaningful relationships between disparate stimuli in ways that escape conscious awareness. Processes active during sleep can strengthen these relationships, leading to more adaptive use of those stimuli when encountered during subsequent wake. Performance on the weather prediction task (WPT), a well-studied measure of implicit probabilistic learning, has been shown to improve significantly following a night of sleep, with stronger initial learning predicting more nocturnal REM sleep. We investigated this relationship further, studying the effect on WPT performance of a daytime nap containing REM sleep. We also added an interference condition after the nap/wake period as an additional probe of memory strength. Our results show that a nap significantly boosts WPT performance, and that this improvement is correlated with the amount of REM sleep obtained during the nap. When interference training is introduced following the nap, however, this REM-sleep benefit vanishes. In contrast, following an equal period of wake, performance is both unchanged from training and unaffected by interference training. Thus, while the true probabilistic relationships between WPT stimuli are strengthened by sleep, these changes are selectively susceptible to the destructive effects of retroactive interference, at least in the short term. PMID:25769506

  10. Loss of Gnas Imprinting Differentially Affects REM/NREM Sleep and Cognition in Mice

    PubMed Central

    Lassi, Glenda; Ball, Simon T.; Maggi, Silvia; Colonna, Giovanni; Nieus, Thierry; Cero, Cheryl; Bartolomucci, Alessandro; Peters, Jo; Tucci, Valter

    2012-01-01

    It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM–linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT) and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM–dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes. PMID:22589743

  11. REM sleep enhancement of probabilistic classification learning is sensitive to subsequent interference.

    PubMed

    Barsky, Murray M; Tucker, Matthew A; Stickgold, Robert

    2015-07-01

    During wakefulness the brain creates meaningful relationships between disparate stimuli in ways that escape conscious awareness. Processes active during sleep can strengthen these relationships, leading to more adaptive use of those stimuli when encountered during subsequent wake. Performance on the Weather Prediction Task (WPT), a well-studied measure of implicit probabilistic learning, has been shown to improve significantly following a night of sleep, with stronger initial learning predicting more nocturnal REM sleep. We investigated this relationship further, studying the effect on WPT performance of a daytime nap containing REM sleep. We also added an interference condition after the nap/wake period as an additional probe of memory strength. Our results show that a nap significantly boosts WPT performance, and that this improvement is correlated with the amount of REM sleep obtained during the nap. When interference training is introduced following the nap, however, this REM-sleep benefit vanishes. In contrast, following an equal period of wake, performance is both unchanged from training and unaffected by interference training. Thus, while the true probabilistic relationships between WPT stimuli are strengthened by sleep, these changes are selectively susceptible to the destructive effects of retroactive interference, at least in the short term. PMID:25769506

  12. REM sleep enhancement of probabilistic classification learning is sensitive to subsequent interference.

    PubMed

    Barsky, Murray M; Tucker, Matthew A; Stickgold, Robert

    2015-07-01

    During wakefulness the brain creates meaningful relationships between disparate stimuli in ways that escape conscious awareness. Processes active during sleep can strengthen these relationships, leading to more adaptive use of those stimuli when encountered during subsequent wake. Performance on the Weather Prediction Task (WPT), a well-studied measure of implicit probabilistic learning, has been shown to improve significantly following a night of sleep, with stronger initial learning predicting more nocturnal REM sleep. We investigated this relationship further, studying the effect on WPT performance of a daytime nap containing REM sleep. We also added an interference condition after the nap/wake period as an additional probe of memory strength. Our results show that a nap significantly boosts WPT performance, and that this improvement is correlated with the amount of REM sleep obtained during the nap. When interference training is introduced following the nap, however, this REM-sleep benefit vanishes. In contrast, following an equal period of wake, performance is both unchanged from training and unaffected by interference training. Thus, while the true probabilistic relationships between WPT stimuli are strengthened by sleep, these changes are selectively susceptible to the destructive effects of retroactive interference, at least in the short term.

  13. Idiopathic rapid eye movement sleep behaviour disorder: diagnosis, management, and the need for neuroprotective interventions.

    PubMed

    Iranzo, Alex; Santamaria, Joan; Tolosa, Eduardo

    2016-04-01

    Idiopathic rapid eye movement (REM) sleep behaviour disorder (IRBD) manifests as unpleasant dreams and vigorous behaviours during REM sleep that can result in injuries. Patients with IRBD have no known neurological diseases or motor or cognitive complaints; however, this sleep disorder is not harmless. In most cases, IRBD is the prelude of the synucleinopathies Parkinson's disease, dementia with Lewy bodies, or, less frequently, multiple system atrophy. Patients can show abnormalities that are characteristic of the synucleinopathies, and longitudinal follow-up shows that most patients develop parkinsonism and cognitive impairments with time. Thus, diagnosis of IRBD needs to be accurate and involves informing the patient of the risk of developing a neurodegenerative disease. It is extraordinary for a sleep disorder to precede the full expression of a neurodegenerative disease, which renders IRBD of particular interest in studies of the prodromal stage of the synucleinopathies, and in the development of neuroprotective interventions to stop or slow neurodegenerative deterioration before motor and cognitive symptomatology emerges. Such therapeutics do not currently exist, and thus represent an unmet need in IRBD. PMID:26971662

  14. Individual differences in compensatory rebound of REM sleep, with particular reference to their relationship to personality and behavioral characteristics.

    PubMed

    Nakazawa, Y; Kotorii, M; Kotorii, T; Tachibana, H; Nakano, T

    1975-07-01

    In subjecting 14 healthy university students to partial differential rapid eye movement (REM) sleep deprivation (PDRD), the compensatory rebound of REM sleep during the next night was determined, and showed fairly substantial individual differences in the increased percentage of REM sleep time. This rate was approximately the same for the same individual for two sleep recordings. These individual differences had no positive correlation with the decreased rate of REM time in the PDRD nights or with the percentage of REM time in the baseline night. Therefore, the individual differences in the increased percentage of REM time can be presumed to reflect individual differences in need for deprived REM sleep. Next, we looked into the relationship between the individual subject's personality and behavior characteristics, and his increased percentage of REM time. This revealed that the individuals who were extrovertive, active, optimistic, showy, and who had many friends had significantly higher increases in the percentage of REM time than the individuals who were introvertive, neurotic, inactive, nervous, modest, and who had few friends. Also discussed was the neurophysiological and biochemical basis of the central nervous system as the background for the relationship between the personality and behavioral characteristics and the increased percentage of REM sleep time. PMID:168312

  15. REM Sleep and Its Loss-associated Epigenetic Regulation with Reference to Noradrenaline in Particular

    PubMed Central

    Mehta, Rachna; Singh, Abhishek; Bókkon, István; Nath Mallick, Birendra

    2016-01-01

    Sleep is an essential physiological process, which has been divided into rapid eye movement sleep (REMS) and non-REMS (NREMS) in higher animals. REMS is a unique phenomenon that unlike other sleep-waking states is not under voluntary control. Directly or indirectly it influences or gets influenced by most of the physiological processes controlled by the brain. It has been proposed that REMS serves housekeeping function of the brain. Extensive research has shown that during REMS at least noradrenaline (NA) -ergic neurons must cease activity and upon REMS loss, there are increased levels of NA in the brain, which then induces many of the REMS loss associated acute and chronic effects. The NA level is controlled by many bio-molecules that are regulated at the molecular and transcriptional levels. Similarly, NA can also directly or indirectly modulate the synthesis and levels of many molecules, which in turn may affect physiological processes. The burgeoning field of behavioral neuroepigenetics has gained importance in recent years and explains the regulatory mechanisms underlying several behavioral phenomena. As REMS and its loss associated changes in NA modulate several pathophysiological processes, in this review we have attempted to explain on one hand how the epigenetic mechanisms regulating the gene expression of factors like tyrosine hydroxylase (TH), monoamine oxidase (MAO), noradrenaline transporter (NAT) control NA levels and on the other hand, how NA per se can affect other molecules in neural circuitry at the epigenetic level resulting in behavioral changes in health and diseases. An understanding of these events will expose the molecular basis of REMS and its loss-associated pathophysiological changes; which are presented as a testable hypothesis for confirmation. PMID:26813120

  16. Validation of the Mayo Sleep Questionnaire to Screen for REM Sleep Behavior Disorder in a Community-Based Sample

    PubMed Central

    Boeve, Bradley F.; Molano, Jennifer R.; Ferman, Tanis J.; Lin, Siong-Chi; Bieniek, Kevin; Tippmann-Peikert, Maja; Boot, Brendon; St. Louis, Erik K.; Knopman, David S.; Petersen, Ronald C.; Silber, Michael H.

    2013-01-01

    Objective: To validate a questionnaire focused on REM sleep behavior disorder (RBD) in a community-based sample. Background: RBD is a parasomnia manifested by recurrent dream enactment behavior during REM sleep. While confirmation of RBD requires the presence of REM sleep without atonia on polysomnography (PSG), a screening measure for RBD validated in older adults would be desirable for clinical and research purposes. Methods: We had previously developed the Mayo Sleep Questionnaire (MSQ) to screen for the presence of RBD and other sleep disorders. We assessed the validity of the MSQ by comparing the responses of subjects' bed partners with the findings on PSG. All subjects recruited from 10/04 to 12/08 in the Mayo Clinic Study of Aging—a population-based study of aging in Olmsted County, Minnesota—who had also undergone a previous PSG were the focus of this analysis. Results: The study sample included 128 subjects (104 male; median age 77 years [range 67-90]), with the following clinical diagnoses at baseline assessment: normal (n = 95), mild cognitive impairment (n = 30), and mild Alzheimer disease (n = 3). Nine (5%) subjects had RBD based on history and PSG evidence of REM sleep without atonia. The core question on recurrent dream enactment behavior yielded sensitivity (SN) of 100% and specificity (SP) of 95% for the diagnosis of RBD. The profile of responses on four additional subquestions on RBD improved specificity. Conclusions: These data suggest that the MSQ has adequate SN and SP for the diagnosis of RBD among elderly subjects in a community-based sample. Citation: Boeve BF; Molano JR; Ferman TJ; Lin Siong-Chi; Bieniek K; Tippmann-Peikert M; Boot B; St. Louis EK; Knopman DS; Petersen RC; Silber MH. Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in a community-based sample. J Clin Sleep Med 2013;9(5):475-480. PMID:23674939

  17. The effects of sleep deprivation in humans: topographical electroencephalogram changes in non-rapid eye movement (NREM) sleep versus REM sleep.

    PubMed

    Marzano, Cristina; Ferrara, Michele; Curcio, Giuseppe; De Gennaro, Luigi

    2010-06-01

    Studies on homeostatic aspects of sleep regulation have been focussed upon non-rapid eye movement (NREM) sleep, and direct comparisons with regional changes in rapid eye movement (REM) sleep are sparse. To this end, evaluation of electroencephalogram (EEG) changes in recovery sleep after extended waking is the classical approach for increasing homeostatic need. Here, we studied a large sample of 40 healthy subjects, considering a full-scalp EEG topography during baseline (BSL) and recovery sleep following 40 h of wakefulness (REC). In NREM sleep, the statistical maps of REC versus BSL differences revealed significant fronto-central increases of power from 0.5 to 11 Hz and decreases from 13 to 15 Hz. In REM sleep, REC versus BSL differences pointed to significant fronto-central increases in the 0.5-7 Hz and decreases in the 8-11 Hz bands. Moreover, the 12-15 Hz band showed a fronto-parietal increase and that at 22-24 Hz exhibited a fronto-central decrease. Hence, the 1-7 Hz range showed significant increases in both NREM sleep and REM sleep, with similar topography. The parallel change of NREM sleep and REM sleep EEG power is related, as confirmed by a correlational analysis, indicating that the increase in frequency of 2-7 Hz possibly subtends a state-aspecific homeostatic response. On the contrary, sleep deprivation has opposite effects on alpha and sigma activity in both states. In particular, this analysis points to the presence of state-specific homeostatic mechanisms for NREM sleep, limited to <2 Hz frequencies. In conclusion, REM sleep and NREM sleep seem to share some homeostatic mechanisms in response to sleep deprivation, as indicated mainly by the similar direction and topography of changes in low-frequency activity.

  18. REM sleep deprivation attenuates actin-binding protein cortactin: a link between sleep and hippocampal plasticity.

    PubMed

    Davis, Christopher J; Meighan, Peter C; Taishi, Ping; Krueger, James M; Harding, Joseph W; Wright, John W

    2006-06-12

    Rapid eye-movement sleep (REMS) is thought to affect synaptic plasticity. Cortactin is a cytoskeletal protein critically involved in the regulation of actin branching and stabilization including the actin backbone of dendritic spines. Hippocampal cortactin levels, phosphorylation, and processing appear to be altered during learning and long-term potentiation (LTP); consistent with a role for cortactin in the dendritic restructuring that accompanies synaptic plasticity. In this study juvenile male Sprague-Dawley rats were selectively REMS-deprived (RD) for 48 h by the flowerpot method. Cage control (CC) and large pedestal control (PC) animals were used for comparison. Animals were euthanized immediately, or 12 h, after removal from the pedestal. The hippocampus was dissected, flash-frozen, and stored for subsequent Western blot or quantitative RT-PCR analysis of cortactin. Cortactin mRNA/cDNA levels initially rose in PC and RD rats but returned to CC levels by 12 h after removal from the pedestal. Predictably cortactin protein levels were initially unchanged but were up-regulated after 12 h. The PC group had more total and tyrosine-phosphorylated cortactin protein expression than the RD and CC groups. This increase in cortactin was likely due to the exposure of the rats to the novel environment of the deprivation chambers thus triggering plasticity events. The lack of REMS, however, severely hampered cortactin protein up-regulation and phosphorylation observed in the PC group suggesting an attenuation of plasticity-related events. Thus, these data support a functional link between REMS and cytoskeletal reorganization in the hippocampus, a process that is essential for synaptic plasticity.

  19. Vivid dreams, hallucinations, psychosis and REM sleep in Guillain-Barré syndrome.

    PubMed

    Cochen, V; Arnulf, I; Demeret, S; Neulat, M L; Gourlet, V; Drouot, X; Moutereau, S; Derenne, J P; Similowski, T; Willer, J C; Pierrot-Deseiligny, C; Bolgert, F

    2005-11-01

    We conducted a prospective controlled study of the clinical and biological determinants of the mental status abnormalities in 139 patients with Guillain-Barré syndrome (GBS) and 55 patients without GBS placed in the intensive care unit (ICU controls). There were mental status changes in 31% of GBS patients and in 16% of controls (odds ratio = 2.3; P = 0.04). In GBS patients, they included vivid dreams (19%), illusions (30%, including an illusory body tilt), hallucinations (60%, mainly visual) and delusions (70%, mostly paranoid). They appeared a median 9 days after disease onset (range 1-40 days, during the progression or the plateau of the disease), and lasted a median 8 days. Seven (16%) patients experienced the symptoms before their admission to the ICU. Hallucinations were frequently hypnagogic, occurring as soon as the patients closed their eyes. Autonomic dysfunction, assisted ventilation and high CSF protein levels were significant risk factors for abnormal mental status in GBS patients. CSF hypocretin-1 (a hypothalamic neuropeptide deficient in narcolepsy) levels, measured in 20 patients, were lower in GBS patients with hallucinations (555 +/- 132 pg/ml) than in those without (664 +/- 71 pg/ml, P = 0.03). Since the mental status abnormalities had dream-like aspects, we examined their association with rapid eye movement sleep (REM sleep) using continuous sleep monitoring in 13 GBS patients with (n = 7) and without (n = 6) hallucinations and 6 tetraplegic ICU controls without hallucinations. Although sleep was short and fragmented in all groups, REM sleep latency was shorter in GBS patients with hallucinations (56 +/- 115 min) than in GBS patients without hallucinations (153 +/- 130 min) and in controls (207 +/- 179 min, P < 0.05). In addition, sleep structure was highly abnormal in hallucinators, with sleep onset in REM sleep periods (83%), abnormal eye movements during non-REM sleep (57%), high percentages of REM sleep without atonia (92 +/- 22%), REM

  20. Rapid-Eye-Movement-Sleep (REM) Associated Enhancement of Working Memory Performance after a Daytime Nap.

    PubMed

    Lau, Esther Yuet Ying; Wong, Mark Lawrence; Lau, Kristy Nga Ting; Hui, Florence Wai Ying; Tseng, Chia-huei

    2015-01-01

    The main objective was to study the impact of a daytime sleep opportunity on working memory and the mechanism behind such impact. This study adopted an experimental design in a sleep research laboratory. Eighty healthy college students (Age:17-23, 36 males) were randomized to either have a polysomnography-monitored daytime sleep opportunity (Nap-group, n=40) or stay awake (Wake-group, n=40) between the two assessment sessions. All participants completed a sleep diary and wore an actigraph-watch for 5 days before and one day after the assessment sessions. They completed the state-measurement of sleepiness and affect, in addition to a psychomotor vigilance test and a working memory task before and after the nap/wake sessions. The two groups did not differ in their sleep characteristics prior to and after the lab visit. The Nap-group had higher accuracy on the working memory task, fewer lapses on the psychomotor vigilance test and lower state-sleepiness than the Wake-group. Within the Nap-group, working memory accuracy was positively correlated with duration of rapid eye movement sleep (REM) and total sleep time during the nap. Our findings suggested that "sleep gain" during a daytime sleep opportunity had significant positive impact on working memory performance, without affecting subsequent nighttime sleep in young adult, and such impact was associated with the duration of REM. While REM abnormality has long been noted in pathological conditions (e.g. depression), which are also presented with cognitive dysfunctions (e.g. working memory deficits), this was the first evidence showing working memory enhancement associated with REM in daytime napping in college students, who likely had habitual short sleep duration but were otherwise generally healthy. PMID:25970511

  1. Rapid-Eye-Movement-Sleep (REM) Associated Enhancement of Working Memory Performance after a Daytime Nap

    PubMed Central

    Lau, Kristy Nga Ting; Hui, Florence Wai Ying; Tseng, Chia-huei

    2015-01-01

    The main objective was to study the impact of a daytime sleep opportunity on working memory and the mechanism behind such impact. This study adopted an experimental design in a sleep research laboratory. Eighty healthy college students (Age:17-23, 36 males) were randomized to either have a polysomnography-monitored daytime sleep opportunity (Nap-group, n=40) or stay awake (Wake-group, n=40) between the two assessment sessions. All participants completed a sleep diary and wore an actigraph-watch for 5 days before and one day after the assessment sessions. They completed the state-measurement of sleepiness and affect, in addition to a psychomotor vigilance test and a working memory task before and after the nap/wake sessions. The two groups did not differ in their sleep characteristics prior to and after the lab visit. The Nap-group had higher accuracy on the working memory task, fewer lapses on the psychomotor vigilance test and lower state-sleepiness than the Wake-group. Within the Nap-group, working memory accuracy was positively correlated with duration of rapid eye movement sleep (REM) and total sleep time during the nap. Our findings suggested that “sleep gain” during a daytime sleep opportunity had significant positive impact on working memory performance, without affecting subsequent nighttime sleep in young adult, and such impact was associated with the duration of REM. While REM abnormality has long been noted in pathological conditions (e.g. depression), which are also presented with cognitive dysfunctions (e.g. working memory deficits), this was the first evidence showing working memory enhancement associated with REM in daytime napping in college students, who likely had habitual short sleep duration but were otherwise generally healthy. PMID:25970511

  2. Rapid-Eye-Movement-Sleep (REM) Associated Enhancement of Working Memory Performance after a Daytime Nap.

    PubMed

    Lau, Esther Yuet Ying; Wong, Mark Lawrence; Lau, Kristy Nga Ting; Hui, Florence Wai Ying; Tseng, Chia-huei

    2015-01-01

    The main objective was to study the impact of a daytime sleep opportunity on working memory and the mechanism behind such impact. This study adopted an experimental design in a sleep research laboratory. Eighty healthy college students (Age:17-23, 36 males) were randomized to either have a polysomnography-monitored daytime sleep opportunity (Nap-group, n=40) or stay awake (Wake-group, n=40) between the two assessment sessions. All participants completed a sleep diary and wore an actigraph-watch for 5 days before and one day after the assessment sessions. They completed the state-measurement of sleepiness and affect, in addition to a psychomotor vigilance test and a working memory task before and after the nap/wake sessions. The two groups did not differ in their sleep characteristics prior to and after the lab visit. The Nap-group had higher accuracy on the working memory task, fewer lapses on the psychomotor vigilance test and lower state-sleepiness than the Wake-group. Within the Nap-group, working memory accuracy was positively correlated with duration of rapid eye movement sleep (REM) and total sleep time during the nap. Our findings suggested that "sleep gain" during a daytime sleep opportunity had significant positive impact on working memory performance, without affecting subsequent nighttime sleep in young adult, and such impact was associated with the duration of REM. While REM abnormality has long been noted in pathological conditions (e.g. depression), which are also presented with cognitive dysfunctions (e.g. working memory deficits), this was the first evidence showing working memory enhancement associated with REM in daytime napping in college students, who likely had habitual short sleep duration but were otherwise generally healthy.

  3. REM sleep changes in rats induced by siRNA-mediated orexin knockdown.

    PubMed

    Chen, Lichao; Thakkar, Mahesh M; Winston, Stuart; Bolortuya, Yunren; Basheer, Radhika; McCarley, Robert W

    2006-10-01

    Short interfering RNAs (siRNA) targeting prepro-orexin mRNA were microinjected into the rat perifornical hypothalamus. Prepro-orexin siRNA-treated rats had a significant (59%) reduction in prepro-orexin mRNA compared to scrambled siRNA-treated rats 2 days postinjection, whereas prodynorphin mRNA was unaffected. The number of orexin-A-positive neurons on the siRNA-treated side decreased significantly (23%) as compared to the contralateral control (scrambled siRNA-treated) side. Neither the colocalized dynorphin nor the neighbouring melanin-concentrating hormone neurons were affected. The number of orexin-A-positive neurons on the siRNA-treated side did not differ from the number on the control side 4 or 6 days postinjection. Behaviourally, there was a persistent (approximately 60%) increase in the amount of time spent in rapid eye movement (REM) sleep during the dark (active) period for 4 nights postinjection, in rats treated with prepro-orexin siRNA bilaterally. This increase occurred mainly because of an increased number of REM episodes and decrease in REM-to-REM interval. Cataplexy-like episodes were also observed in some of these animals. Wakefulness and NREM sleep were unaffected. The siRNA-induced increase in REM sleep during the dark cycle reverted to control values on the 5th day postinjection. In contrast, the scrambled siRNA-treated animals only had a transient increase in REM sleep for the first postinjection night. Our results indicate that siRNA can be usefully employed in behavioural studies to complement other loss-of-function approaches. Moreover, these data suggest that the orexin system plays a role in the diurnal gating of REM sleep.

  4. Melatonin Therapy for REM Sleep Behavior Disorder: A Critical Review of Evidence

    PubMed Central

    Leung, Jonathan G.; St Louis, Erik K.; Boeve, Bradley F.

    2014-01-01

    REM sleep behavior disorder (RBD) is a parasomnia associated with dream enactment often involving violent or potentially injurious behaviors during REM sleep that is strongly associated with synucleinopathy neurodegeneration. Clonazepam has long been suggested as the first-line treatment option for RBD. However, evidence supporting melatonin therapy is expanding. Melatonin appears to be beneficial for the management of RBD with reductions in clinical behavioral outcomes and decrease in muscle tonicity during REM sleep. Melatonin also has a favorable safety and tolerability profile over clonazepam with limited potential for drug-drug interactions, an important consideration especially in elderly individuals with RBD receiving polypharmacy. Prospective clinical trials are necessary to establish evidence-basis for melatonin and clonazepam as RBD therapies. PMID:25454845

  5. Melatonin therapy for REM sleep behavior disorder: a critical review of evidence.

    PubMed

    McGrane, Ian R; Leung, Jonathan G; St Louis, Erik K; Boeve, Bradley F

    2015-01-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia associated with dream enactment often involving violent or potentially injurious behaviors during REM sleep that is strongly associated with synucleinopathy neurodegeneration. Clonazepam has long been suggested as the first-line treatment option for RBD. However, evidence supporting melatonin therapy is expanding. Melatonin appears to be beneficial for the management of RBD with reductions in clinical behavioral outcomes and decrease in muscle tonicity during REM sleep. Melatonin also has a favorable safety and tolerability profile over clonazepam with limited potential for drug-drug interactions, an important consideration especially in elderly individuals with RBD receiving polypharmacy. Prospective clinical trials are necessary to establish the evidence basis for melatonin and clonazepam as RBD therapies. PMID:25454845

  6. Microinjection of the melanin-concentrating hormone into the sublaterodorsal tegmental nucleus inhibits REM sleep in the rat.

    PubMed

    Monti, Jaime M; Torterolo, Pablo; Jantos, Héctor; Lagos, Patricia

    2016-09-01

    A study was performed on the effects of local microinjection of melanin-concentrating hormone (MCH) into the right sublaterodorsal tegmental nucleus (SLD) on sleep and wakefulness in rats prepared for chronic sleep recordings. MCH 200ng significantly decreased rapid-eye-movement sleep (REMS) time during the first and second 2-h of the recording period which was related to the reduction of the number of REMS periods and the increase of REMS latency. It is proposed that REMS inhibition was related to the direct deactivation of SLD glutamatergic neurons by the peptide. PMID:27461793

  7. Increased REM sleep after intra-locus coeruleus nucleus microinjection of melanin-concentrating hormone (MCH) in the rat.

    PubMed

    Monti, Jaime M; Lagos, Patricia; Jantos, Héctor; Torterolo, Pablo

    2015-01-01

    A study was carried out on the effects of unilateral microinjection of melanin-concentrating hormone (MCH) into the right locus coeruleus (LC) on the sleep-wake cycle in rats prepared for chronic sleep recordings. MCH 200 ng significantly augmented rapid-eye-movement sleep (REMS) time during the first, second and third 2-h of recording. Furthermore, MCH 100 ng induced a significant increase of REMS during the first 2-h period after treatment. The increment of the behavioral state was related to a greater number of REMS episodes. It is suggested that MCH deactivation of noradrenergic neurons located in the LC facilitates the occurrence of REMS.

  8. Affect Intensity and Phasic REM Sleep in Depressed Men before and after Treatment with Cognitive-Behavioral Therapy.

    ERIC Educational Resources Information Center

    Nofzinger, Eric A.; And Others

    1994-01-01

    Explored relationship between daytime affect and REM (rapid eye movement) sleep in 45 depressed men before and after treatment with cognitive-behavioral therapy and in control group of 43 healthy subjects. For depressed subjects only, intensity of daytime affect correlated significantly and positively with phasic REM sleep measures at pre- and…

  9. Spatial and Reversal Learning in the Morris Water Maze Are Largely Resistant to Six Hours of REM Sleep Deprivation Following Training

    ERIC Educational Resources Information Center

    Walsh, Christine M.; Booth, Victoria; Poe, Gina R.

    2011-01-01

    This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair…

  10. [Modulation by the GABA of the ventro-oral-pontine reticular REM sleep-inducing neurons].

    PubMed

    Reinoso Suárez, Fernando

    2007-01-01

    From a multidisciplinary study in our laboratory we have compiled numerous findings on the role played by the inhibitory neurotransmitter GABA in the ventral part of the oral pontine reticular nucleus (vRPO), REM sleep induction and maintenance brainstem structure. Functional GABA in the vRPO is located in a few small and scattered neuronal bodies, and in an abundant number of synaptic terminals: 30% of all synaptic terminals in vRPO are GABAergic. These terminals form inhibitory, symmetric synapses on the soma and different segments of the dendritic tree of the vRPO neurons, mainly in those of large diameter. In unitary intracellular studies, in vitro, we have demonstrated that GABA produces hyperpolarization of the vRPO neurons. In vivo experiments in freely moving cats, local microinjections of the GABA(A) receptor agonist muscimol decreased REM sleep. The different densities of GABA-immunoreactions and the diverse and complex morphological ultrastructure of the vRPO GABAergic terminals suggest that they have different origins and physiologic functions. There are GABAergic projections to the vRPO from diencephalic structures related with the other phases of the sleep-wakefulness cycle: wakefulness and non-REM sleep, which may be anatomical substrata for the GABAergic inhibition of the vRPO REM sleep-inducing neurons during these other phases.

  11. REM sleep deprivation induces changes of down regulatory antagonist modulator (DREAM) expression in the ventrobasal thalamic nuclei of sprague-dawley rats.

    PubMed

    Siran, Rosfaiizah; Ahmad, Asma Hayati; Abdul Aziz, Che Badariah; Ismail, Zalina

    2014-12-01

    REM sleep is a crucial component of sleep. Animal studies indicate that rapid eye movement (REM) sleep deprivation elicits changes in gene expression. Down regulatory antagonist modulator (DREAM) is a protein which downregulates other gene transcriptions by binding to the downstream response element site. The aim of this study is to examine the effect of REM sleep deprivation on DREAM expression in ventrobasal thalamic nuclei (VB) of rats. Seventy-two male Sprague-Dawley rats were divided into four major groups consisting of free-moving control rats (FMC) (n = 18), 72-h REM sleep-deprived rats (REMsd) (n = 18), 72-h REM sleep-deprived rats with 72-h sleep recovery (RG) (n = 18), and tank control rats (TC) (n = 18). REM sleep deprivation was elicited using the inverted flower pot technique. DREAM expression was examined in VB by immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) studies. The DREAM-positive neuronal cells (DPN) were decreased bilaterally in the VB of rats deprived of REM sleep as well as after sleep recovery. The nuclear DREAM extractions were increased bilaterally in animals deprived of REM sleep. The DREAM messenger RNA (mRNA) levels were decreased after sleep recovery. The results demonstrated a link between DREAM expression and REM sleep deprivation as well as sleep recovery which may indicate potential involvement of DREAM in REM sleep-induced changes in gene expression, specifically in nociceptive processing.

  12. Role of spinal 5-HT receptors in cutaneous hypersensitivity induced by REM sleep deprivation.

    PubMed

    Wei, Hong; Ma, Ainiu; Wang, Yong-Xiang; Pertovaara, Antti

    2008-06-01

    Previous studies indicate that rapid eye movement (REM) sleep deprivation facilitates pain sensitivity. Since serotoninergic raphe neurons are involved both in regulation of sleep and descending pain modulation, we studied whether spinal 5-HT receptors have a role in sleep deprivation-induced facilitation of pain-related behavior. REM sleep deprivation of 48h was induced by the flower pot method in the rat. The pain modulatory influence of various serotoninergic compounds administered intrathecally was assessed by determining limb withdrawal response to monofilaments. REM sleep deprivation produced a marked hypersensitivity. Sleep deprivation-induced hypersensitivity and normal sensitivity in controls were reduced both by a 5-HT(1A) receptor antagonist (WAY-100635) and a 5-HT(2C) receptor antagonist (RS-102221). An antagonist of the 5-HT(3) receptor (LY-278584) failed to modulate hypersensitivity in sleep-deprived or control animals. Paradoxically, sensitivity in sleep-deprived and control animals was reduced not only by a 5-HT(1A) receptor antagonist but also by a 5-HT(1A) receptor agonist (8-OHDPAT). The results indicate that serotoninergic receptors in the spinal cord have a complex role in the control of sleep-deprivation induced cutaneous hypersensitivity as well as baseline sensitivity in control conditions. While endogenous serotonin acting on 5-HT(1A) and 5-HT(2C) receptors may facilitate mechanical sensitivity in animals with a sleep deprivation-induced hypersensitivity as well as in controls, increased activation of spinal 5-HT(1A) receptors by an exogenous agonist leads to suppression of mechanical sensitivity in both conditions. Spinal 5-HT(3) receptors do not contribute to cutaneous hypersensitivity induced by sleep deprivation.

  13. Immunocytochemical distribution of VIP and PACAP in the rat brain stem: implications for REM sleep physiology.

    PubMed

    Ahnaou, Abdel; Yon, Laurent; Arluison, Michel; Vaudry, Hubert; Hannibal, Jens; Hamon, Michel; Adrien, Joelle; Bourgin, Patrice

    2006-07-01

    Recent evidence indicates that pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) might play an important role in rapid eye movement sleep (REMS) generation at the pontine level in rats. We have thus examined the immunohistochemical distribution of VIP and PACAP in the pontine and mesencephalic areas known to be involved in REMS control in rats. A dense network of VIP-immunoreactive cell bodies and fibers was found in the dorsal raphe nucleus. A large number of PACAP-positive perikarya and nerve fibers was observed in the area known as the REMS induction zone within the pontine reticular formation (PRF). The present results provide an anatomical basis to our previous functional data, and suggest that PACAPergic mechanisms within the PRF play a critical role in long-term regulation of REMS.

  14. Activation of serotonin 5-HT(1B) receptor in the dorsal raphe nucleus affects REM sleep in the rat.

    PubMed

    Monti, Jaime M; Jantos, Héctor; Lagos, Patricia

    2010-01-01

    The effects of CP-94253, a selective 5-HT(1B) receptor agonist, and of SB 224-289, a selective 5-HT(1B) receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The 5-HT(1B) receptor ligands were microinjected directly into the dorsal raphe nucleus (DRN) during the light period of the 12-h light/12-h dark cycle. Infusion of CP-94253 (1-4 mM) into the DRN induced a significant reduction of rapid-eye-movement sleep (REMS) and of the mean duration of REM episodes. On the other hand, SB 224-289 (0.25-0.5 mM) decreased REMS and the number of REM periods. Pretreatment with SB 224-289 (0.125-0.25 mM) antagonized the CP-94253 (4 mM)-induced reduction of REMS and of the mean duration of REM periods. Administration of the GABA(A) receptor agonist muscimol (1.5mM), which by itself did not significantly affect sleep variables, prevented the effect of CP-94253 (4 mM) on REMS suppression. It is proposed that the suppression of REMS after microinjection of CP-94253 into the DRN is related to the inhibition of GABAergic interneurons that make synaptic contacts with serotonergic cells. The resultant increase of serotonin release at postsynaptic sites involved in the induction and maintenance of REMS would induce the suppression of the behavioral state.

  15. The Prevalence and Characteristics of REM Sleep without Atonia (RSWA) in Patients Taking Antidepressants

    PubMed Central

    Lee, Kenneth; Baron, Kelly; Soca, Rodolfo; Attarian, Hrayr

    2016-01-01

    Study Objectives: The association of REM sleep without atonia (RSWA) as well as REM sleep behavior disorder (RBD) with the intake of selective serotonin reuptake inhibitors (SSRI) and selective norepinephrine reuptake inhibitors (SNRI) is well established. Our study objective was to determine the prevalence of RSWA and RBD among a group of sleep center patients taking SSRI and SNRI. Methods: A retrospective chart review was done at our tertiary sleep center, and 10,746 consecutive records from October 1, 2007, through October 31, 2013, were searched for SSRI and SNRI names using the Sleep Cataloguer Software. Results: The search resulted in 1,444 records, which were then reviewed for keywords of RSWA and RBD. The AASM scoring criteria were used to determine RSWA. Reports of 41 patients with known narcolepsy or α-synucleinopathies were excluded. The remaining records were mined for age, sex, presence of obstructive sleep apnea (OSA), type of antidepressant (SSRI or SNRI), and diagnosis for which antidepressant was prescribed. We used logistic regression analysis to adjust for age, OSA, and sex. Of the 1,444 participants on antidepressants, 176 (12.2%) had RSWA (all confirmed by the investigators) compared to 226 of the entire sleep lab population of 10,746 (2.1%), risk ratio (95% CI) 9.978 (8.149, 12.22). Seven of the 176 patients on antidepressants had RBD (0.48%) compared to 108 of 10,746 (1%), p = 0.005. Conclusions: SSRI and SNRI are associated with a higher prevalence of RSWA but not of RBD. This is independent of medication type. Citation: Lee K, Baron K, Soca R, Attarian H. The prevalence and characteristics of rem sleep without atonia (RSWA) in patients taking antidepressants. J Clin Sleep Med 2016;12(3):351–355. PMID:26446247

  16. Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

    PubMed Central

    Datta, Subimal; O'Malley, Matthew W .

    2013-01-01

    Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372

  17. Exposure to dim artificial light at night increases REM sleep and awakenings in humans.

    PubMed

    Cho, Chul-Hyun; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Kang, Seung-Gul; Bok, Ki-Nam; Jung, Ki-Young; Kim, Leen; Lee, Eun-Il

    2016-01-01

    Exposure to artificial light at night (ALAN) has become increasing common, especially in developed countries. We investigated the effect of dALAN exposure during sleep in healthy young male subjects. A total of 30 healthy young male volunteers from 21 to 29 years old were recruited for the study. They were randomly divided into two groups depending on light intensity (Group A: 5 lux and Group B: 10 lux). After a quality control process, 23 healthy subjects were included in the study (Group A: 11 subjects, Group B: 12 subjects). Subjects underwent an NPSG session with no light (Night 1) followed by an NPSG session randomly assigned to two different dim light conditions (5 or 10 lux, dom λ: 501.4 nm) for a whole night (Night 2). We found significant sleep structural differences between Nights 1 and 2, but no difference between Groups A and B. Exposure to dALAN during sleep was significantly associated with increased wake time after sleep onset (WASO; F = 7.273, p = 0.014), increased Stage N1 (F = 4.524, p = 0.045), decreased Stage N2 (F = 9.49, p = 0.006), increased Stage R (F = 6.698, p = 0.017) and non-significantly decreased REM density (F = 4.102, p = 0.056). We found that dALAN during sleep affects sleep structure. Exposure to dALAN during sleep increases the frequency of arousals, amount of shallow sleep and amount of REM sleep. This suggests adverse effects of dALAN during sleep on sleep quality and suggests the need to avoid exposure to dALAN during sleep.

  18. Effects of age on recovery of body weight following REM sleep deprivation of rats.

    PubMed

    Koban, Michael; Stewart, Craig V

    2006-01-30

    Chronically enforced rapid eye (paradoxical) movement sleep deprivation (REM-SD) of rats leads to a host of pathologies, of which hyperphagia and loss of body weight are among the most readily observed. In recent years, the etiology of many REM-SD-associated pathologies have been elucidated, but one unexplored area is whether age affects outcomes. In this study, male Sprague-Dawley rats at 2, 6, and 12 months of age were REM sleep-deprived with the platform (flowerpot) method for 10-12 days. Two-month-old rats resided on 7-cm platforms, while 10-cm platforms were used for 6- and 12-month-old rats; rats on 15-cm platforms served as tank controls (TCs). Daily changes in food consumption (g/kg(0.67)) and body weight (g) during baseline, REM-SD or TCs, and post-experiment recovery in home cages were determined. Compared to TCs, REM-SD resulted in higher food intake and decreases in body weight. When returned to home cages, food intake rapidly declined to baseline levels. Of primary interest was that rates of body weight gain during recovery differed between the age groups. Two-month-old rats rapidly restored body weight to pre-REM-SD mass within 5 days; 6-month-old rats were extrapolated by linear regression to have taken about 10 days, and for 12-month-old rats, the estimate was about 35 days. The observation that restoration of body weight following its loss during REM-SD may be age-dependent is in general agreement with the literature on aging effects on how mammals respond to stress. PMID:16243367

  19. The Clinical Phenotype of Idiopathic Rapid Eye Movement Sleep Behavior Disorder at Presentation: A Study in 203 Consecutive Patients

    PubMed Central

    Fernández-Arcos, Ana; Iranzo, Alex; Serradell, Mónica; Gaig, Carles; Santamaria, Joan

    2016-01-01

    Objective: To describe the clinical phenotype of idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) at presentation in a sleep center. Methods: Clinical history review of 203 consecutive patients with IRBD identified between 1990 and 2014. IRBD was diagnosed by clinical history plus video-polysomnographic demonstration of REM sleep with increased electromyographic activity linked to abnormal behaviors. Results: Patients were 80% men with median age at IRBD diagnosis of 68 y (range, 50–85 y). In addition to the already known clinical picture of IRBD, other important features were apparent: 44% of the patients were not aware of their dream-enactment behaviors and 70% reported good sleep quality. In most of these cases bed partners were essential to convince patients to seek medical help. In 11% IRBD was elicited only after specific questioning when patients consulted for other reasons. Seven percent did not recall unpleasant dreams. Leaving the bed occurred occasionally in 24% of subjects in whom dementia with Lewy bodies often developed eventually. For the correct diagnosis of IRBD, video-polysomnography had to be repeated in 16% because of insufficient REM sleep or electromyographic artifacts from coexistent apneas. Some subjects with comorbid obstructive sleep apnea reported partial improvement of RBD symptoms following continuous positive airway pressure therapy. Lack of therapy with clonazepam resulted in an increased risk of sleep related injuries. Synucleinopathy was frequently diagnosed, even in patients with mild severity or uncommon IRBD presentations (e.g., patients who reported sleeping well, onset triggered by a life event, nocturnal ambulation) indicating that the development of a neurodegenerative disease is independent of the clinical presentation of IRBD. Conclusions: We report the largest IRBD cohort observed in a single center to date and highlight frequent features that were not reported or not sufficiently emphasized in previous

  20. A restricted parabrachial pontine region is active during non-REM sleep

    PubMed Central

    Torterolo, Pablo; Sampogna, Sharon; Chase, Michael H.

    2011-01-01

    The principal site that generates both REM sleep and wakefulness is located in the mesopontine reticular formation, whereas non-REM sleep (NREM) is primarily dependent upon the functioning of neurons that are located in the preoptic region of the hypothalamus. In the present study, we were interested in determining whether the occurrence of NREM might also depend on the activity of mesopontine structures, as has been shown for wakefulness and REM sleep. Adult cats were maintained in one of the following states: quiet wakefulness (QW), alert wakefulness (AW), NREM, or REM sleep induced by microinjections of carbachol into the nucleus pontis oralis (REM-carbachol). Subsequently, they were euthanized and single labeling immunohistochemical studies were undertaken to determine state-dependent patterns of neuronal activity in the brainstem based upon the expression of the protein Fos. In addition, double labeling immunohistochemical studies were carried out to detect neurons that expressed Fos as well as choline acetyltransferase, tyrosine hydroxylase or GABA. During NREM, only a few Fos immunoreactive cells were present in different regions of the brainstem; however, a discrete cluster of Fos+ neurons was observed in the caudolateral peribrachial region (CLPB). The number of the Fos+ neurons in the CLPB during NREM was significantly greater (67.9 ± 10.9, P < 0.0001) compared to QW (8.0 ± 6.7), AW (5.2 ± 4.2) or REM-carbachol (8.0 ± 4.7). In addition, there was a positive correlation (R = 0.93) between the time the animals spent in NREM and the number of Fos+ neurons in the CLPB. Fos-immunoreactive neurons in the CLPB were neither cholinergic nor catecholaminergic; however about 50% of these neurons were GABAergic. We conclude that a group of GABAergic and unidentified neurons in the CLPB are active during NREM and likely involved in the control of this behavioral state. These data open new avenues for the study of NREM, as well as for the explorations of

  1. REM sleep EEG spectral analysis in patients with first-episode schizophrenia.

    PubMed

    Poulin, Julie; Stip, Emmanuel; Godbout, Roger

    2008-10-01

    The pathophysiology of schizophrenia includes abnormalities in subcortical-cortical transfer of information that can be studied using REM sleep EEG spectral analysis, a measure that reflects spontaneous and endogenous thalamocortical activity. We recorded 10 patients with first-episode schizophrenia and 30 healthy controls for two consecutive nights in a sleep laboratory, using a 10-electrode EEG montage. Sixty seconds of REM sleep EEG without artifact were analyzed using FFT spectral analysis. Absolute and relative spectral amplitudes of five frequency bands (delta, theta, alpha, beta1 and beta2) were extracted and compared between the two groups. Frequency bands with significant differences were correlated with BPRS positive and negative symptoms scores. Patients with schizophrenia showed lower relative alpha and higher relative beta2 spectral amplitudes compared to healthy controls over the averaged total scalp. Analysis using cortical regions showed lower relative alpha over frontal, central and temporal regions and higher relative beta2 over the occipital region. Absolute spectral amplitude was not different between groups for any given EEG band. However, absolute alpha activity correlated negatively with BPRS positive symptoms scores and correlated positively with negative symptoms scores. Since similar results have been reported following EEG spectral analysis during the waking state, we conclude that abnormalities of subcortical-cortical transfer of information in schizophrenia could be generated by mechanisms common to REM sleep and waking. PMID:18280502

  2. A Change of Possible Neurological and Psychological Significance Within the First Week of Neonate Life: Sleeping REM Rate.

    ERIC Educational Resources Information Center

    Minard, James; And Others

    The percentage of rapid eye movement (REM) during sleep is substantially greater in neonates (infants in first month after birth) than in other children or adults. It was hypothesized that REM rate may decline as rates of many response sequences do when repeatedly elicited. Electrical recordings of eye movements were obtained from a 3-day-old male…

  3. Prolonged confusion with nocturnal wandering arising from NREM and REM sleep: a case report.

    PubMed

    Kushida, C A; Clerk, A A; Kirsch, C M; Hotson, J R; Guilleminault, C

    1995-11-01

    A 51-year-old man with Machado-Joseph disease had a 3-year history of prolonged confusion following nightly nocturnal wandering. Polysomnography with videotape monitoring revealed 19- to 120-minute sleepwalking episodes emerging from non-rapid eye movement (NREM) sleep and occasionally from rapid eye movement (REM) sleep, followed by 22-47 minutes of prolonged confusion and disorientation. The patient also had a periodic limb movement disorder and obstructive sleep apnea syndrome. Excessive daytime sleepiness was evident by results from the Epworth Sleepiness Scale and Multiple Sleep Latency Test. A sleep-deprived electroencephalogram (EEG) and a polysomnogram with an expanded EEG montage before and during these episodes revealed no epileptiform activity. A contrast-enhanced brain magnetic resonance imaging (MRI) scan demonstrated findings consistent only with Machado-Joseph disease. The patient improved with a combination of temazepam and carbidopa-levodopa. PMID:8638068

  4. REM sleep loss associated changes in orexin-A levels in discrete brain areas in rats.

    PubMed

    Mehta, Rachna; Khanday, Mudasir Ahmad; Mallick, Birendra Nath

    2015-03-17

    Rapid eye movement sleep (REMS) serves house-keeping function of the brain and its loss affects several pathophysiological processes. Relative levels of neurotransmitters including orexin A (Orx-A) in various parts of the brain in health and diseases are among the key factors for modulation of behaviors, including REMS. The level of neurotransmitter in an area in the brain directly depends on number of projecting neurons and their firing rates. The locus coeruleus (LC), the site of REM-OFF neurons, receives densest, while the pedunculo-pontine area (PPT), the site of REM-ON neurons receives lesser projections from the Orx-ergic neurons. Further, the Orx-ergic neurons are active during waking and silent during REMS and NREMS. Therefore, the level of Orx-A in discrete regions of the brain is likely to be different during normal and altered states, which in turn is likely to be responsible for altered behaviors in health and diseases, including in relation to REMS. Therefore, in the present study, we estimated Orx-A level in LC, cortex, posterior hypothalamus (PH), hippocampus, and PPT after 96 h REMSD, in post-deprivation recovered rats and in control rats. This is the first report of estimation of Orx-A in different brain regions after prolonged REMSD. It was observed that after REMSD the Orx-A level increased significantly in LC, cortex and PH which returned to normal level after recovery; however, the level did not change in the hippocampus and PPT. The Orx-A induced modulation of REMS could be secondary to increased waking.

  5. Pattern of REM sleep occurrence in continuous darkness following the exposure to low ambient temperature in the rat.

    PubMed

    Zamboni, G; Amici, R; Perez, E; Jones, C A; Parmeggiani, P L

    2001-07-01

    The occurrence of REM sleep episodes, separated by intervals >3 min (single episodes) and < or =3 min (sequential episodes), was determined in the rat during the recovery (ambient temperature (Ta) 23 degrees C, L period of the LD [12 h:12 h]-cycle), which followed the exposure to low Ta (0 and -10 degrees C) during the D period of the previous LD-cycle, either in normal light (DL) or in continuous darkness (DD). Both exposures were characterized by an almost complete disappearance of REM sleep, whilst the recoveries showed an increase in the amount of REM sleep in the form of sequential episodes, which in DD was particularly prominent and concomitant with a decrease in the amount of REM sleep in the form of single episodes. The initial 2 h-rate of REM sleep occurrence was lower following the exposure to Ta -10 degrees C, than to Ta 0 degrees C. In DD, such an effect was due to the large reduction in the occurrence of sequential REM sleep episodes. A functional correlate of this finding is that the accumulation capacity of a second messenger (cAMP) was found to be lower at the end of the exposure to Ta -10 degrees C, with respect to both the control (Ta 23 degrees C) and the end of exposure to Ta 0 degrees C, in the preoptic-anterior hypothalamus, but not in the cerebral cortex.

  6. GABAA receptors are located in cholinergic terminals in the nucleus pontis oralis of the rat: implications for REM sleep control.

    PubMed

    Liang, Chang-Lin; Marks, Gerald A

    2014-01-16

    The oral pontine reticular formation (PnO) of rat is one region identified in the brainstem as a rapid eye movement (REM) sleep induction zone. Microinjection of GABA(A) receptor antagonists into PnO induces a long lasting increase in REM sleep, which is similar to that produced by cholinergic agonists. We previously showed that this REM sleep-induction can be completely blocked by a muscarinic antagonist, indicating that the REM sleep-inducing effect of GABA(A) receptor antagonism is dependent upon the local cholinergic system. Consistent with these findings, it has been reported that GABA(A) receptor antagonists microdialyzed into PnO resulted in increased levels of acetylcholine. We hypothesize that GABA(A) receptors located on cholinergic boutons in the PnO are responsible for the REM sleep induction by GABA(A) receptor antagonists through blocking GABA inhibition of acetylcholine release. Cholinergic, varicose axon fibers were studied in the PnO by immunofluorescence and confocal, laser scanning microscopy. Immunoreactive cholinergic boutons were found to be colocalized with GABA(A) receptor subunit protein γ2. This finding implicates a specific subtype and location of GABA(A) receptors in PnO of rat in the control of REM sleep. PMID:24141149

  7. Age-related effects of bilateral frontal eye fields lesions on rapid eye movements during REM sleep in rhesus monkeys.

    PubMed

    Yu, Shan; Liu, Ning; Zeng, Tao; Tian, Shaohua; Chen, Nanhui; Zhou, Yifeng; Ma, Yuanye

    2004-08-01

    Rapid eye movement (REM) is one of the most characteristic features of REM sleep, but the mechanisms underlying its regulation remain unclear. The present study aims to investigate whether the frontal eye field (FEF) is involved in the regulation of the rapid eye movements during REM sleep. To address this question, we ablated the FEF in four rhesus monkeys and observed the effects of the lesions on sleep architecture. After lesions, two adult monkeys did not show any lesion effect. However, in the other two adolescent monkeys, both the total duration and percentage of the rapid eye movements during REM sleep were decreased moderately. The result suggests that the relation between the FEF and the regulation of the rapid eye movements during REM sleep may be affected by age factor, also indicating that both the functions of the FEF and the mechanisms underlying the control of rapid eye movements during REM sleep might not be the same throughout the whole life span of an animal. PMID:15265590

  8. Noradrenaline acting on alpha1-adrenoceptor mediates REM sleep deprivation-induced increased membrane potential in rat brain synaptosomes.

    PubMed

    Das, Gitanjali; Mallick, Birendra Nath

    2008-01-01

    We hypothesized that one of the functions of REM sleep is to maintain brain excitability and therefore, REM sleep deprivation is likely to modulate neuronal transmembrane potential; however, so far there was no direct evidence to support the claim. In this study a cationic dye, 3,3'-diethylthiacarbocyanine iodide was used to estimate the potential in synaptosomal samples prepared from control and REM sleep deprived rat brains. The activity of Na-K-ATPase that maintains the transmembrane potential was also estimated in the same sample. Further, the roles of noradrenaline and alpha1-adrenoceptor in mediating the responses were studied both in vivo as well as in vitro. Rats were REM sleep deprived for 4 days by the classical flower-pot method; large platform and recovery controls were carried out in addition to free-moving control. The fluorescence intensity increased in samples prepared from REM sleep deprived rat brain as compared to control, which reflected synaptosomal depolarization after deprivation. The Na-K-ATPase activity also increased in the same deprived sample. Furthermore, both the effects were mediated by noradrenaline acting on alpha1-adrenoceptors in the brain. This is the first direct evidence showing that REM sleep deprivation indeed increased neuronal depolarization, which is the likely cause for increased brain excitability, thus supporting our hypothesis and the effect was mediated by noradrenaline acting through the alpha1-adrenoceptor.

  9. Testosterone not associated with violent dreams or REM sleep behavior disorder in men with Parkinson's.

    PubMed

    Chou, Kelvin L; Moro-De-Casillas, Maria L; Amick, Melissa M; Borek, Leora L; Friedman, Joseph H

    2007-02-15

    We examined the relationship between testosterone levels, violent dreams, and REM sleep behavior disorder (RBD) in 31 men with Parkinson's disease (PD): 12 with clinical RBD and 19 without. All PD patients with clinical RBD experienced violent dreams, but none of the 19 non-RBD patients reported violent dreams. While dream content appears to be more aggressive in PD patients with clinical RBD, the presence of violent dreams or clinical RBD is not associated with testosterone levels in men with PD.

  10. Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats.

    PubMed

    Herrera-Solís, Andrea; Vásquez, Khalil Guzmán; Prospéro-García, Oscar

    2010-03-01

    Anandamide and oleamide, induce sleep when administered acutely, via the CB1 receptor. Their subchronic administration must be tested to demonstrate the absence of tolerance to this effect, and that the sudden withdrawal of these endocannabinoids (eCBs) does not affect sleep negatively. The sleep-waking cycle of rats was evaluated for 24h, under the effect of an acute or subchronic administration of eCBs, and during sudden eCBs withdrawal. AM251, a CB1 receptor antagonist (CB1Ra) was utilized to block eCBs effects. Our results indicated that both acute and subchronic administration of eCBs increase REMS. During eCBs withdrawal, rats lack the expression of an abstinence-like syndrome. AM251 was efficacious to prevent REMS increase caused by both acute and subchronic administration of these eCBs, suggesting that this effect is mediated by the CB1 receptor. Our data further support a role of the eCBs in REMS regulation.

  11. Evidence that non-dreamers do dream: a REM sleep behaviour disorder model.

    PubMed

    Herlin, Bastien; Leu-Semenescu, Smaranda; Chaumereuil, Charlotte; Arnulf, Isabelle

    2015-12-01

    To determine whether non-dreamers do not produce dreams or do not recall them, subjects were identified with no dream recall with dreamlike behaviours during rapid eye movement sleep behaviour disorder, which is typically characterised by dream-enacting behaviours congruent with sleep mentation. All consecutive patients with idiopathic rapid eye movement sleep behaviour disorder or rapid eye movement sleep behaviour disorder associated with Parkinson's disease who underwent a video-polysomnography were interviewed regarding the presence or absence of dream recall, retrospectively or upon spontaneous arousals. The patients with no dream recall for at least 10 years, and never-ever recallers were compared with dream recallers with rapid eye movement sleep behaviour disorder regarding their clinical, cognitive and sleep features. Of the 289 patients with rapid eye movement sleep behaviour disorder, eight (2.8%) patients had no dream recall, including four (1.4%) patients who had never ever recalled dreams, and four patients who had no dream recall for 10-56 years. All non-recallers exhibited, daily or almost nightly, several complex, scenic and dreamlike behaviours and speeches, which were also observed during rapid eye movement sleep on video-polysomnography (arguing, fighting and speaking). They did not recall a dream following sudden awakenings from rapid eye movement sleep. These eight non-recallers with rapid eye movement sleep behaviour disorder did not differ in terms of cognition, clinical, treatment or sleep measures from the 17 dreamers with rapid eye movement sleep behaviour disorder matched for age, sex and disease. The scenic dreamlike behaviours reported and observed during rapid eye movement sleep in the rare non-recallers with rapid eye movement sleep behaviour disorder (even in the never-ever recallers) provide strong evidence that non-recallers produce dreams, but do not recall them. Rapid eye movement sleep behaviour disorder provides a new model to

  12. Evidence that non-dreamers do dream: a REM sleep behaviour disorder model.

    PubMed

    Herlin, Bastien; Leu-Semenescu, Smaranda; Chaumereuil, Charlotte; Arnulf, Isabelle

    2015-12-01

    To determine whether non-dreamers do not produce dreams or do not recall them, subjects were identified with no dream recall with dreamlike behaviours during rapid eye movement sleep behaviour disorder, which is typically characterised by dream-enacting behaviours congruent with sleep mentation. All consecutive patients with idiopathic rapid eye movement sleep behaviour disorder or rapid eye movement sleep behaviour disorder associated with Parkinson's disease who underwent a video-polysomnography were interviewed regarding the presence or absence of dream recall, retrospectively or upon spontaneous arousals. The patients with no dream recall for at least 10 years, and never-ever recallers were compared with dream recallers with rapid eye movement sleep behaviour disorder regarding their clinical, cognitive and sleep features. Of the 289 patients with rapid eye movement sleep behaviour disorder, eight (2.8%) patients had no dream recall, including four (1.4%) patients who had never ever recalled dreams, and four patients who had no dream recall for 10-56 years. All non-recallers exhibited, daily or almost nightly, several complex, scenic and dreamlike behaviours and speeches, which were also observed during rapid eye movement sleep on video-polysomnography (arguing, fighting and speaking). They did not recall a dream following sudden awakenings from rapid eye movement sleep. These eight non-recallers with rapid eye movement sleep behaviour disorder did not differ in terms of cognition, clinical, treatment or sleep measures from the 17 dreamers with rapid eye movement sleep behaviour disorder matched for age, sex and disease. The scenic dreamlike behaviours reported and observed during rapid eye movement sleep in the rare non-recallers with rapid eye movement sleep behaviour disorder (even in the never-ever recallers) provide strong evidence that non-recallers produce dreams, but do not recall them. Rapid eye movement sleep behaviour disorder provides a new model to

  13. Caffeine and REM sleep deprivation: Effect on basal levels of signaling molecules in area CA1.

    PubMed

    Alkadhi, Karim A; Alhaider, Ibrahim A

    2016-03-01

    We have investigated the neuroprotective effect of chronic caffeine treatment on basal levels of memory-related signaling molecules in area CA1 of sleep-deprived rats. Animals in the caffeine groups were treated with caffeine in drinking water (0.3g/l) for four weeks before they were REM sleep-deprived for 24h in the Modified Multiple Platforms paradigm. Western blot analysis of basal protein levels of plasticity- and memory-related signaling molecules in hippocampal area CA1 showed significant down regulation of the basal levels of phosphorylated- and total-CaMKII, phosphorylated- and total-CREB as well as those of BDNF and CaMKIV in sleep deprived rats. All these changes were completely prevented in rats that chronically consumed caffeine. The present findings suggest an important neuroprotective property of caffeine in sleep deprivation.

  14. Caffeine and REM sleep deprivation: Effect on basal levels of signaling molecules in area CA1.

    PubMed

    Alkadhi, Karim A; Alhaider, Ibrahim A

    2016-03-01

    We have investigated the neuroprotective effect of chronic caffeine treatment on basal levels of memory-related signaling molecules in area CA1 of sleep-deprived rats. Animals in the caffeine groups were treated with caffeine in drinking water (0.3g/l) for four weeks before they were REM sleep-deprived for 24h in the Modified Multiple Platforms paradigm. Western blot analysis of basal protein levels of plasticity- and memory-related signaling molecules in hippocampal area CA1 showed significant down regulation of the basal levels of phosphorylated- and total-CaMKII, phosphorylated- and total-CREB as well as those of BDNF and CaMKIV in sleep deprived rats. All these changes were completely prevented in rats that chronically consumed caffeine. The present findings suggest an important neuroprotective property of caffeine in sleep deprivation. PMID:26767416

  15. A Classification method for eye movements direction during REM sleep trained on wake electro-oculographic recordings

    PubMed Central

    Betta, M.; Laurino, M.; Gemignani, A.; Landi, A.; Menicucci, D.

    2016-01-01

    Rapid eye movements (REMs) are a peculiar and intriguing aspect of REM sleep, even if their physiological function still remains unclear. During this work, a new automatic tool was developed, aimed at a complete description of REMs activity during the night, both in terms of their timing of occurrence that in term of their directional properties. A classification stage of each singular movement detected during the night according to its main direction, was in fact added to our procedure of REMs detection and ocular artifact removal. A supervised classifier was constructed, using as training and validation set EOG data recorded during voluntary saccades of five healthy volunteers. Different classification methods were tested and compared. The further information about REMs directional characteristic provided by the procedure would represent a valuable tool for a deeper investigation into REMs physiological origin and functional meaning. PMID:26736276

  16. Serotonin turnover in different duration of sleep recovery in discrete regions of young rat brain after 24 h REM sleep deprivation.

    PubMed

    Senthilvelan, M; Ravindran, R; Samson, J; Devi, R Sheela

    2006-09-01

    Sleep plays an important role in restorative function and serotonin (5-hydroxytryptamine: 5HT) equally plays important roles in sleep. Though various studies have revealed the roles of 5HT in sleep/wake cycle, the mechanism involved is yet unclear. In the present study we investigated alteration of the 5HT turnover in various regions of the young rat brains after 24 hours (h) REM sleep (sREM) deprivation to elucidate the roles of 5HT in sleep restoration function in the these regions. The 5HT turnover was evaluated by the ratio of 5-hydroxyindole acetic acid against 5HT. The sREM deprivation was performed by the inverted flowerpot technique. The 5HT turnover showed significant alteration in the all regions of the brain examined after 24h sREM deprivation, particular depending on the brain region. These results revealed that sREM modulates the 5HT turnover in the brain with region specificity and this may be one of the restorative functions of sleep indicating that sREM is regionally generated.

  17. Don't count your chickens before they're hatched: elaborative encoding in REM dreaming in face of the physiology of sleep stages.

    PubMed

    Deliens, Gaétane; Schwartz, Sophie; Peigneux, Philippe

    2013-12-01

    Llewellyn suggests that episodic memories undergo "elaborative encoding" during rapid eye movement (REM) dreams, generating novel associations between recent and remote memories that are then instantiated during non-REM (NREM) sleep. This hypothesis conflicts with our knowledge of the physiology of NREM and then REM sleep stages and their ordered succession. Moreover, associations during sleep might also involve the extraction of hidden patterns rather than de novo associations.

  18. Modafinil treatment prevents REM sleep deprivation-induced brain function impairment by increasing MMP-9 expression.

    PubMed

    He, Bin; Peng, Hua; Zhao, Ying; Zhou, Hui; Zhao, Zhongxin

    2011-12-01

    Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil treatment prevented REM-SD-induced impairment of cognitive function. Modafinil significantly reduced the number of errors compared to placebo and upregulated synapsin I expression in the dorsal hippocampal CA3 region. A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats.

  19. Sleep and cognition at baseline and the effects of REM sleep diminution after 1 week of antidepressive treatment in patients with depression.

    PubMed

    Göder, Robert; Seeck-Hirschner, Mareen; Stingele, Karoline; Huchzermeier, Christian; Kropp, Cornelia; Palaschewski, Milena; Aldenhoff, Josef; Koch, Jakob

    2011-12-01

    It has been hypothesized that non-rapid eye movement (NREM) sleep facilitates declarative memory consolidation, and rapid eye movement (REM) sleep is particularly important in promoting procedural learning. The aim of this study was to examine the effects of pharmacological REM sleep suppression on performance in different neuropsychological tasks. For our baseline, we chose 41 moderately depressed patients (age range 19-44 years), who were not taking antidepressants. In the morning after polysomnography, we tested memory recall and cognitive flexibility by assessment of verbal and figural fluency, a shift of attention task and the Trail Making Test B. After recording baseline values, patients were assigned randomly to one of three treatment groups: medication with citalopram; medication with reboxetine; or exclusive treatment with psychotherapy. Retesting took place 1 week after onset of treatment. The main results were: (1) an association of slow-wave sleep with verbal memory performance at baseline; (2) a suppression of REM sleep in patients taking citalopram and reboxetine; (3) no differences regarding neuropsychological performance within the treatment groups; and (4) no association of REM sleep diminution with decreases in memory performance or cognitive flexibility in patients treated with citalopram or reboxetine. In line with other studies, our results suggest that there are no negative effects of a decrease in REM sleep on memory performance in patients taking antidepressants.

  20. Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and REM Sleep.

    PubMed

    Urbano, Francisco J; D'Onofrio, Stasia M; Luster, Brennon R; Beck, Paige B; Hyde, James Robert; Bisagno, Veronica; Garcia-Rill, Edgar

    2014-01-01

    The pedunculopontine nucleus (PPN) is a major component of the reticular activating system (RAS) that regulates waking and REM sleep, states of high-frequency EEG activity. Recently, we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine PPN, intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. That is, the RAS may play an early permissive role in volition. Our latest results suggest that (1) the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, (3) leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and (4) following our discovery of electrical coupling in the RAS, we hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS.

  1. Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and REM Sleep

    PubMed Central

    Urbano, Francisco J.; D’Onofrio, Stasia M.; Luster, Brennon R.; Beck, Paige B.; Hyde, James Robert; Bisagno, Veronica; Garcia-Rill, Edgar

    2014-01-01

    The pedunculopontine nucleus (PPN) is a major component of the reticular activating system (RAS) that regulates waking and REM sleep, states of high-frequency EEG activity. Recently, we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine PPN, intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. That is, the RAS may play an early permissive role in volition. Our latest results suggest that (1) the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, (3) leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and (4) following our discovery of electrical coupling in the RAS, we hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS. PMID:25368599

  2. Sleep before and after learning promotes the consolidation of both neutral and emotional information regardless of REM presence.

    PubMed

    Cellini, Nicola; Torre, Jacopo; Stegagno, Luciano; Sarlo, Michela

    2016-09-01

    Sleep may play a role in consolidating emotional memories. However, studies on the effects of REM sleep on negative vs. neutral memories have produced inconsistent evidence. Here, we assess the role of NREM and REM sleep before and after learning in promoting the consolidation of neutral and arousing pleasant and unpleasant memories. Forty-six (32 F) healthy university students were exposed to a set of pictures at 1:00PM (Session 1) and to an equivalent set at 4:45PM (Session 2). All the pictures in Session 1 and Session 2 were presented again, intermixed with new similar pictures at 5:15PM in a memory recognition task. Following Session 1, participants took a 90/120-min nap (NAP group), while 16 participants remained awake (WAKE group). Via polysomnographic recording, the NAP group was segregated into REM (N=14) and NoREM groups (N=16). Indices of memory consolidation for both stimuli presented before (discriminability of Session 1 pictures in Session 3) and after sleep (discriminability of Session 2 pictures in Session 3) were calculated. Memory consolidation for pictures presented both before and after the sleep period was higher in the NAP group as compared to the WAKE group, but no differential role of REM sleep emerged. A memory consolidation advantage was evident for neutral over pleasant (but not unpleasant) pictures. Taken together, these results indicate that a daytime nap (with or without REM sleep) facilitates consolidation of declarative memories presented before and after sleep irrespective of their valence. PMID:27321589

  3. Aminergic and cholinergic afferents to REM sleep induction regions of the pontine reticular formation in the rat.

    PubMed

    Semba, K

    1993-04-22

    Microinjection of cholinergic agonists in a dorsolateral part of the mesopontine tegmentum has been shown to induce a rapid eye movement (REM) sleep-like state. Physiological evidence indicates that not only acetylcholine but also various amine transmitters, including those implicated in behavioral state regulation, affect neuronal activity in this region of the pontine reticular formation. In the present study, sources of select aminergic and cholinergic inputs to this REM sleep induction zone were identified and quantitatively analyzed by using fluorescence retrograde tracing combined with immunofluorescence in the rat. In addition to previously demonstrated cholinergic projections from the pedunculopontine and laterodorsal tegmental nuclei, the REM sleep induction zone received various aminergic inputs that originated in widely distributed regions of the brainstem and hypothalamus. Serotoninergic afferents represented a mean of 44% of all aminergic/cholinergic source neurons projecting to the REM sleep induction zone, which was comparable to the mean percentage of 39% represented by cholinergic afferent neurons. The serotoninergic afferents originated from the raphe nuclei at all brainstem levels, with heavier projections from the pontine than from the medullary raphe nuclei. Unexpectedly, an additional major serotoninergic input was provided by serotoninergic neurons in the nucleus prosupralemniscus (B9). Noradrenergic afferent neurons represented a mean of 14% of all aminergic/cholinergic source neurons, which was only about one-third of the mean percentage of either cholinergic or serotoninergic source neurons. These noradrenergic projection neurons were located not only in the locus ceruleus (8%) but also in the lateral tegmentum, including the A5 (4%) and A7 (2%) cell groups. Histaminergic neurons in the tuberomammillary hypothalamic nucleus represented a minor group of afferent neurons (3%), and a still smaller input came from adrenergic C1 neurons. The

  4. Trauma Associated Sleep Disorder: A Proposed Parasomnia Encompassing Disruptive Nocturnal Behaviors, Nightmares, and REM without Atonia in Trauma Survivors

    PubMed Central

    Mysliwiec, Vincent; O'Reilly, Brian; Polchinski, Jason; Kwon, Herbert P.; Germain, Anne; Roth, Bernard J.

    2014-01-01

    Study Objectives: To characterize the clinical, polysomnographic and treatment responses of patients with disruptive nocturnal behaviors (DNB) and nightmares following traumatic experiences. Methods: A case series of four young male, active duty U.S. Army Soldiers who presented with DNB and trauma related nightmares. Patients underwent a clinical evaluation in a sleep medicine clinic, attended overnight polysomnogram (PSG) and received treatment. We report pertinent clinical and PSG findings from our patients and review prior literature on sleep disturbances in trauma survivors. Results: DNB ranged from vocalizations, somnambulism to combative behaviors that injured bed partners. Nightmares were replays of the patient's traumatic experiences. All patients had REM without atonia during polysomnography; one patient had DNB and a nightmare captured during REM sleep. Prazosin improved DNB and nightmares in all patients. Conclusions: We propose Trauma associated Sleep Disorder (TSD) as a unique sleep disorder encompassing the clinical features, PSG findings, and treatment responses of patients with DNB, nightmares, and REM without atonia after trauma. Citation: Mysliwiec V, O'Reilly B, Polchinski J, Kwon HP, Germain A, Roth BJ. Trauma associated sleep disorder: a proposed parasomnia encompassing disruptive nocturnal behaviors, nightmares, and REM without atonia in trauma survivors. J Clin Sleep Med 2014;10(10):1143-1148. PMID:25317096

  5. Altered functional connectivity in lesional peduncular hallucinosis with REM sleep behavior disorder.

    PubMed

    Geddes, Maiya R; Tie, Yanmei; Gabrieli, John D E; McGinnis, Scott M; Golby, Alexandra J; Whitfield-Gabrieli, Susan

    2016-01-01

    Brainstem lesions causing peduncular hallucinosis (PH) produce vivid visual hallucinations occasionally accompanied by sleep disorders. Overlapping brainstem regions modulate visual pathways and REM sleep functions via gating of thalamocortical networks. A 66-year-old man with paroxysmal atrial fibrillation developed abrupt-onset complex visual hallucinations with preserved insight and violent dream enactment behavior. Brain MRI showed restricted diffusion in the left rostrodorsal pons suggestive of an acute ischemic stroke. REM sleep behavior disorder (RBD) was diagnosed on polysomnography. We investigated the integrity of ponto-geniculate-occipital circuits with seed-based resting-state functional connectivity MRI (rs-fcMRI) in this patient compared to 46 controls. Rs-fcMRI revealed significantly reduced functional connectivity between the lesion and lateral geniculate nuclei (LGN), and between LGN and visual association cortex compared to controls. Conversely, functional connectivity between brainstem and visual association cortex, and between visual association cortex and prefrontal cortex (PFC) was significantly increased in the patient. Focal damage to the rostrodorsal pons is sufficient to cause RBD and PH in humans, suggesting an overlapping mechanism in both syndromes. This lesion produced a pattern of altered functional connectivity consistent with disrupted visual cortex connectivity via de-afferentation of thalamocortical pathways.

  6. [REM sleep modulation by non-GABAergic neurons of the hypothalamus and basal forebrain].

    PubMed

    Reinoso Suárez, Fernando

    2010-01-01

    The ventral part of the oral pontine reticular nucleus (vRPO) is a demonstrated site of brainstem REM-sleep generation and maintenance. The vRPO has reciprocal connections with structures that control other states of the sleep-wakefulness cycle, many situated in the basal forebrain and the diencephalon. The aim of the present revision is to map, using the results described in previous publications of our group, the local origin of the basal forebrain and hypothalamus non-GABAergic projections to the vRPO, and specially the contribution of the hypothalamic neurons positive to hypocretin/orexin (H/O) peptides. I summarize non-GABAergic projections to the vRPO from the: ipsilateral central amygdaline nucleus and the stria terminalis bed nuclei, bilateral projections, but most abundant in the ipsilateral side, from the median preoptic nucleus, medial and lateral preoptic areas, abundant from the zona incerta and dorsal, lateral, posterior and perifornical hypothalamic areas. Very abundant bilateral projections of H/O neurons to the vRPO are described, expressive of the important modulation exerted by these neurons on the vRPO nucleus. I discuss the functional significance of the above results and the corresponding mechanisms, supported by physiological and ultrastructural results of our group. Based on the connections and action mechanisms of H/O neurons on the vRPO, which produce the decreased activity of neurons in this nucleus and, therefore, inhibition of REM sleep, I reflect briefly on narcolepsy pathophysiology.

  7. A brainstem inflammatory lesion causing REM sleep behavior disorder and sleepwalking (parasomnia overlap disorder).

    PubMed

    Limousin, Nadège; Dehais, Caroline; Gout, Olivier; Héran, Françoise; Oudiette, Delphine; Arnulf, Isabelle

    2009-10-01

    A 40-year-old woman with no prior parasomnia developed an acute inflammatory rhombencephalitis with multiple cranial nerve palsies and cerebellar ataxia, followed by myelitis 6 months later, and by an intracranial thrombophlebitis 1 month after. Between and after these episodes, she had a persistent, mild right internuclear ophtalmoplegia, a mild cerebellar ataxia, and a severe REM sleep behavior disorder (RBD) lasting for 2 years. She talked, sang and moved nightly while asleep, and injured her son (cosleeping with her) while asleep. In addition, she walked asleep nightly. During video-polysomnography, there were two arousals during slow wave sleep without abnormal behavior, while 44% of REM sleep was without chin muscle atonia with bilateral arm and leg movements. There were small hypointensities in the right pontine tegmentum and in the right dorsal medulla on T1-weighted magnetic resonance imaging, suggesting post-inflammatory lesions that persisted between acute episodes. The RBD and sleepwalking did not improve with clonazepam, but improved with melatonin 9 mg/d. The unilateral small lesion of the pontine tegmentum could be responsible for the parasomnia overlap disorder as in other rare lesional cases. PMID:19345142

  8. Altered functional connectivity in lesional peduncular hallucinosis with REM sleep behavior disorder.

    PubMed

    Geddes, Maiya R; Tie, Yanmei; Gabrieli, John D E; McGinnis, Scott M; Golby, Alexandra J; Whitfield-Gabrieli, Susan

    2016-01-01

    Brainstem lesions causing peduncular hallucinosis (PH) produce vivid visual hallucinations occasionally accompanied by sleep disorders. Overlapping brainstem regions modulate visual pathways and REM sleep functions via gating of thalamocortical networks. A 66-year-old man with paroxysmal atrial fibrillation developed abrupt-onset complex visual hallucinations with preserved insight and violent dream enactment behavior. Brain MRI showed restricted diffusion in the left rostrodorsal pons suggestive of an acute ischemic stroke. REM sleep behavior disorder (RBD) was diagnosed on polysomnography. We investigated the integrity of ponto-geniculate-occipital circuits with seed-based resting-state functional connectivity MRI (rs-fcMRI) in this patient compared to 46 controls. Rs-fcMRI revealed significantly reduced functional connectivity between the lesion and lateral geniculate nuclei (LGN), and between LGN and visual association cortex compared to controls. Conversely, functional connectivity between brainstem and visual association cortex, and between visual association cortex and prefrontal cortex (PFC) was significantly increased in the patient. Focal damage to the rostrodorsal pons is sufficient to cause RBD and PH in humans, suggesting an overlapping mechanism in both syndromes. This lesion produced a pattern of altered functional connectivity consistent with disrupted visual cortex connectivity via de-afferentation of thalamocortical pathways. PMID:26656284

  9. REM sleep deprivation increases the expression of interleukin genes in mice hypothalamus.

    PubMed

    Kang, Won Sub; Park, Hae Jeong; Chung, Joo-Ho; Kim, Jong Woo

    2013-11-27

    Recently, evidence has suggested the possible involvement of inflammatory cytokines in sleep deprivation (SD). In this study, we assessed the patterns of inflammatory gene regulation in the hypothalamus of REM SD mice. C57BL/6 mice were randomly assigned to two groups, SD (n=15) and control groups (n=15). Mice in the SD group were sleep-deprived for 72h using modified multiple platforms. Microarray analysis on inflammatory genes was performed in mice hypothalamus. In addition, interleukin 1 beta (IL1β) protein expression was analyzed by the immunochemistry method. Through microarray analysis, we found that expressions of IL subfamily genes, such as IL1β (2.55-fold), IL18 (1.92-fold), IL11 receptor alpha chain 1 (1.48-fold), IL5 (1.41-fold), and IL17E genes (1.31-fold), were up-regulated in the hypothalamus of SD mice compared to the control. The increase in the expression of these genes was also confirmed by RT-PCR. Among these genes, the expression of IL1β was particularly increased in the hypothalamus of SD mice. Interestingly, we found that the protein expression of endogenous IL1β was also elevated in the hypothalamus of SD mice compared to the control mice. These results implicate that IL subfamily genes, and in particular, IL1β, may play a role in sleep regulation in the hypothalamus of REM SD mice.

  10. A brainstem inflammatory lesion causing REM sleep behavior disorder and sleepwalking (parasomnia overlap disorder).

    PubMed

    Limousin, Nadège; Dehais, Caroline; Gout, Olivier; Héran, Françoise; Oudiette, Delphine; Arnulf, Isabelle

    2009-10-01

    A 40-year-old woman with no prior parasomnia developed an acute inflammatory rhombencephalitis with multiple cranial nerve palsies and cerebellar ataxia, followed by myelitis 6 months later, and by an intracranial thrombophlebitis 1 month after. Between and after these episodes, she had a persistent, mild right internuclear ophtalmoplegia, a mild cerebellar ataxia, and a severe REM sleep behavior disorder (RBD) lasting for 2 years. She talked, sang and moved nightly while asleep, and injured her son (cosleeping with her) while asleep. In addition, she walked asleep nightly. During video-polysomnography, there were two arousals during slow wave sleep without abnormal behavior, while 44% of REM sleep was without chin muscle atonia with bilateral arm and leg movements. There were small hypointensities in the right pontine tegmentum and in the right dorsal medulla on T1-weighted magnetic resonance imaging, suggesting post-inflammatory lesions that persisted between acute episodes. The RBD and sleepwalking did not improve with clonazepam, but improved with melatonin 9 mg/d. The unilateral small lesion of the pontine tegmentum could be responsible for the parasomnia overlap disorder as in other rare lesional cases.

  11. Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training.

    PubMed

    Walsh, Christine M; Booth, Victoria; Poe, Gina R

    2011-07-01

    This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair both hippocampus-dependent spatial learning and learning a new target location within a familiar environment: reversal learning. A 6-d protocol was divided into the initial spatial learning phase (3.5 d) immediately followed by the reversal phase (2.5 d). During the 6 h following four or 12 training trials/day of initial or reversal learning phases, REM sleep was eliminated and non-REM sleep left intact using the multiple inverted flowerpot method. Contrary to our hypotheses, REM sleep deprivation during four or 12 trials/day of initial spatial or reversal learning did not affect training performance. However, some probe trial measures indicated REM sleep-deprivation-associated impairment in initial spatial learning with four trials/day and enhancement of subsequent reversal learning. In naive animals, REM sleep deprivation during normal initial spatial learning was followed by a lack of preference for the subsequent reversal platform location during the probe. Our findings contradict reports that REM sleep is essential for spatial learning in the Morris water maze and newly reveal that short periods of REM sleep deprivation do not impair concurrent reversal learning. Effects on subsequent reversal learning are consistent with the idea that REM sleep serves the consolidation of incompletely learned items.

  12. The effects of 1 week of REM sleep deprivation on parvalbumin and calbindin immunoreactive neurons in central visual pathways of kittens.

    PubMed

    Hogan, D; Roffwarg, H P; Shaffery, J P

    2001-12-01

    Many maturational processes in the brain are at high levels prenatally as well as neonatally before eye-opening, when extrinsic sensory stimulation is limited. During these periods of rapid brain development, a large percentage of time is spent in rapid eye movement (REM) sleep, a state characterized by high levels of endogenously produced brain activity. The abundance of REM sleep in early life and its ensuing decline to lower levels in adulthood strongly suggest that REM sleep constitutes an integral part of the activity-dependent processes that enable normal physiological and structural brain development. We examined the effect of REM sleep deprivation during the critical period for visual development on the development of two calcium-binding proteins that are associated with developmental synaptic plasticity and are found in the lateral geniculate nucleus (LGN) and visual cortex. In this study, REM sleep deprivation was carried out utilizing a computer-controlled, cage-shaking apparatus that successfully suppressed REM sleep. Body weight data suggested that this method of REM sleep deprivation produced less stress than the classical multiple-platform-over-water method. In REM sleep-deprived animals with normal binocular vision, the number of parvalbumin-immunoreactive (PV) neurons in LGN was found to be lower compared with control animals but was not affected in visual cortex. The pattern of calbindin-immunoreactivity (CaB) was unchanged at either site after REM sleep deprivation. Parvalbumin-immunoreactivity develops later than calbindin-immunoreactivity in the LGN, and the REM sleep deprivation that we applied from postnatal day 42-49 delayed this essential step in the development of the kitten's visual system. These data suggest that in early postnatal brain development, REM sleep facilitates the usual time course of the expression of PV-immunoreactivity in LGN neurons.

  13. Effects of playing a computer game using a bright display on presleep physiological variables, sleep latency, slow wave sleep and REM sleep.

    PubMed

    Higuchi, Shigekazu; Motohashi, Yutaka; Liu, Yang; Maeda, Akira

    2005-09-01

    Epidemiological studies have shown that playing a computer game at night delays bedtime and shortens sleeping hours, but the effects on sleep architecture and quality have remained unclear. In the present study, the effects of playing a computer game and using a bright display on nocturnal sleep were examined in a laboratory. Seven male adults (24.7+/-5.6 years old) played exciting computer games with a bright display (game-BD) and a dark display (game-DD) and performed simple tasks with low mental load as a control condition in front of a BD (control-BD) and DD (control-DD) between 23:00 and 1:45 hours in randomized order and then went to bed at 2:00 hours and slept until 8:00 hours. Rectal temperature, electroencephalogram (EEG), heart rate and subjective sleepiness were recorded before sleep and a polysomnogram was recorded during sleep. Heart rate was significantly higher after playing games than after the control conditions, and it was also significantly higher after using the BD than after using the DD. Subjective sleepiness and relative theta power of EEG were significantly lower after playing games than after the control conditions. Sleep latency was significantly longer after playing games than after the control conditions. REM sleep was significantly shorter after the playing games than after the control conditions. No significant effects of either computer games or BD were found on slow-wave sleep. These results suggest that playing an exciting computer game affects sleep latency and REM sleep but that a bright display does not affect sleep variables.

  14. REM Sleep Behavior and Motor Findings in Parkinson's Disease: A Cross-sectional Analysis

    PubMed Central

    Mahajan, Abhimanyu; Rosenthal, Liana S.; Gamaldo, Charlene; Salas, Rachel E.; Pontone, Gregory M.; McCoy, Arita; Umeh, Chizoba; Mari, Zoltan

    2014-01-01

    Background Parkinson's disease (PD) represents a major public health challenge that will only grow in our aging population. Understanding the connection between PD and associated prodromal conditions, such as rapid eye movement sleep behavioral disorder (RBD), is critical to identifying prevention strategies. However, the relationship between RBD and severity of motor findings in early PD is unknown. This study aims to examine this relationship. Methods The study population consisted of 418 PD patients who completed the Movement Disorders Society-United Parkinson's Disease Rating Scale (MDS-UPDRS) and rapid eye movement sleep (REM) disorder questionnaires at the baseline visit of the Michael J. Fox's Parkinson's Progression Markers Initiative (PPMI). Cross-sectional analysis was carried out to assess the association between REM Sleep Behavior Screening Questionnaire score and MDS UPDRS-3 (motor) score categories. Correlation with a higher score category was described as “worse motor findings”. A score of 5 on the REM disorder questionnaire was defined as predictive of RBD. Results Out of the 418 PD patients, 113 (27.0%) had RBD. With univariate logistic regression analysis, individuals with scores predictive of RBD were 1.66 times more likely to have worse motor findings (p = 0.028). Even with age, gender, and Geriatric Depression Scale scores taken into account, individuals with scores predictive of RBD were 1.69 times more likely to have worse motor findings (p = 0.025). Discussion PD patients with RBD symptoms had worse motor findings than those unlikely to have RBD. This association provides further evidence for the relationship between RBD and PD. PMID:25009765

  15. Brain distribution of c-fos expression as a result of prolonged rapid eye movement (REM) sleep period duration.

    PubMed

    Merchant-Nancy, H; Vázquez, J; García, F; Drucker-Colín, R

    1995-05-29

    Auditory stimulation (AS) or recovery from sleep deprivation (SD) has been shown to increase REM sleep periods in rats, cats and humans. This increment in REM has been credited to an amplified level of excitability in a widely distributed neuronal network throughout the brain. Fos-like immunostaining (FLI) has been useful in constructing maps of post-synaptic neuronal activity with single cell resolution, and has been proposed to be tightly related with progressing neuronal activation. This study utilized FLI as a marker to determine the number of neurons and structures which express c-fos in broadly distributed areas of the brain in animals with REM periods prolonged by either AS or SD. The results indicated that the brain stem and diencephalon present FLI increases in a variety of structures that possibly share various functional aspects of the REM sleep mechanism. These results are discussed in terms of the possibility that REM maintenance is related to an increase in the recruitment of REM-on neurons.

  16. Effects of REM sleep deprivation on sensorimotor gating and startle habituation in rats: role of social isolation in early development.

    PubMed

    Chang, Hsin-An; Liu, Yia-Ping; Tung, Che-Se; Chang, Chuan-Chia; Tzeng, Nian-Sheng; Huang, San-Yuan

    2014-07-11

    The present study examined the role of rapid eye movement (REM) sleep on sensorimotor gating function in a developmentally rodent model of schizophrenic-spectrum disorders. Startle magnitude, prepulse inhibition (PPI) and startle habituation in an acoustic startle test were measured after 72-h of REM sleep deprivation (REMSD) in 14-week-old rats that were reared in one of the following conditions: control social interaction, 2-week isolation, and continuous isolation, since weaning. The results showed that REMSD significantly inhibited rats' PPI in socially controlled rats, and rats in two isolation groups appeared less sensitive to REMSD. After REMSD, startle habituation was significantly reduced in continuous-isolated rats but not in 2-week-isolated rats. These data indicate that REM sleep is essential for PPI; REMSD inhibits startle habituation in rats with continuous social isolation. In addition, social interaction, in early life or for the whole life, functions differently to the sensorimotor gating.

  17. Odor Identification Test in Idiopathic REM-Behavior Disorder and Parkinson's Disease in China

    PubMed Central

    Wu, Jian-Jun; Liu, Feng-Tao; Zhao, Jue; Lin, Wei; Guo, Si-Si; Wang, Yi-Xuan; Wang, Ying; Luo, Su-Shan; Sun, Yi-Min; Ding, Zheng-Tong; Yu, Huan; Wang, Jian

    2016-01-01

    Background Olfactory dysfunction is common in Parkinson's disease (PD) and idiopathic rapid eye movement sleep behavior disorder (iRBD), which is a risk factor in the development of PD. However, a few studies have conflicting results when comparing dysosmia in the patients with iRBD and PD. There is no study investigating the olfactory function in Chinese patients with iRBD. Additionally, the Sniffin’ Sticks screening 12 test (SS-12) contains several odors that are not familiar to people in different cultures. Methods Odor identification was evaluated in iRBD patients (n = 54), PD patients (n = 54) and healthy controls (n = 54). With the identification data, a brief odor identification test was established and then validated in other subjects. Results Odor identification scores in iRBD patients were significantly higher than those in PD patients (P<0.001) but lower than those in controls (P<0.001). At the cut-off value of 7.5, the Sniffin’ Sticks clearly differentiated iRBD and PD patients from the controls, and the brief test could increase the specificity in diagnosing PD. Neither the Sniffin’ Sticks nor the brief test could clearly differentiate PD and iRBD patients from each other. Conclusions Olfaction is more impaired in PD patients than in iRBD patients, possibly due to the heterogeneity of iRBD patients. The Sniffin’ Sticks could be a useful tool for differentiating iRBD patients from the healthy population, and it could be useful for screening people at high-risk of PD in China, especially when combined with polysomnography. To reduce the expense and time required for the Sniffin’ Sticks test, this study shows that a brief test is feasible. PMID:27483429

  18. The effects of total and REM sleep deprivation on laser-evoked potential threshold and pain perception.

    PubMed

    Azevedo, Eduardo; Manzano, Gilberto M; Silva, Andressa; Martins, Raquel; Andersen, Monica L; Tufik, Sergio

    2011-09-01

    We investigated the effects of total and rapid eye movement (REM) sleep deprivation on the thermal nociceptive threshold and pain perception using the objective laser-evoked potential (LEP) and the subjective visual analogue scale (VAS). Twenty-eight male adult volunteers were assigned into Control (CTRL), Total (T-SD), and REM (REM-SD) Sleep Deprivation groups. The T-SD and REM-SD volunteers were totally or selectively deprived of sleep for 2 and 4 consecutive nights, respectively. Pain parameters were measured daily during the experimental period. Volunteers were stimulated on the back of the hand by blocks of 50 diode laser pulses. Intensities increased between successive blocks, ranging from nonnoxious to noxious levels, and the LEP threshold was identified based on the evoked-response onset. Both the LEP threshold and VAS ratings were significantly increased after the second night of T-SD. No significant variations were observed in the REM-SD group, suggesting a predominant role for slow wave sleep rather than selective REM-SD in pain perception. Also, for both sleep-deprived groups, the mean values of the LEP threshold and VAS ratings showed a gradual increase that was proportional to the SD deprivation time, followed by a decrease after 1 night of sleep restoration. These findings demonstrate a hyperalgesic modification to pain perception (as reflected by the augmented VAS) and a concomitant increase in the LEP threshold following T-SD, an apparently contradictory effect that can be explained by differences in the ways that attention affects these pain measurements.

  19. Adenosine A1 receptors mediate inhibition of cAMP formation in vitro in the pontine, REM sleep induction zone.

    PubMed

    Marks, Gerald A; Birabil, Christian G; Speciale, Samuel G

    2005-11-01

    Microinjection of adenosine A1 receptor agonist or an inhibitor of adenylyl cyclase into the caudal, oral pontine reticular formation (PnOc) of the rat induces a long-lasting increase in REM sleep. Here, we report significant inhibition of forskolin-stimulated cAMP in dissected pontine tissue slices containing the PnOc incubated with the A1 receptor agonist, cyclohexaladenosine (10(-8) M). These data are consistent with adenosine A1 receptor agonist actions on REM sleep mediated through inhibition of cAMP.

  20. Rapid eye movement (REM) sleep deprivation in 6-OHDA nigro-striatal lesioned rats with and without transplants of dissociated chromaffin cells.

    PubMed

    Drucker-Colín, R; Durán-Vázquez, A; Salín-Pascual, R J; Verdugo-Díaz, L; Mendoza-Ramírez, J L; Jiménez-Anguiano, A

    1996-08-12

    Since both REM sleep deprivation and unilateral 6-OHDA lesions induce supersensitivity of DA receptors, the purpose of this study was to determine whether the response of rats with such lesions would be modified by REM sleep deprivation. In addition, the effect of grafts of dissociated chromaffin cells was also tested. Rats with 6-OHDA lesions were subjected to 24 or 72 h of REM sleep deprivation and tested with various doses of apomorphine to determine turning behavior frequencies. At end of those experiments, the animals were transplanted with dissociated chromaffin cells and turning behavior was tested again. The results showed that REM sleep deprivation nearly doubled the turning behavior frequency, that chromaffin cell grafts decreased it, but that REM deprivation in grafted animals still seemed to produce an increase of post-synaptic supersensitivity independent of denervation. The results were discussed in terms of the possible relationship of sleep with Parkinson's disease through the DA system.

  1. Perchance to dream? Primordial motor activity patterns in vertebrates from fish to mammals: their prenatal origin, postnatal persistence during sleep, and pathological reemergence during REM sleep behavior disorder.

    PubMed

    Corner, Michael A; Schenck, Carlos H

    2015-12-01

    An overview is presented of the literature dealing with sleep-like motility and concomitant neuronal activity patterns throughout the life cycle in vertebrates, ectothermic as well as endothermic. Spontaneous, periodically modulated, neurogenic bursts of non-purposive movements are a universal feature of larval and prenatal behavior, which in endothermic animals (i.e. birds and mammals) continue to occur periodically throughout life. Since the entire body musculature is involved in ever-shifting combinations, it is proposed that these spontaneously active periods be designated as 'rapid-BODY-movement' (RBM) sleep. The term 'rapid-EYE-movement (REM) sleep', characterized by attenuated muscle contractions and reduced tonus, can then be reserved for sleep at later stages of development. Mature stages of development in which sustained muscle atonia is combined with 'paradoxical arousal' of cortical neuronal firing patterns indisputably represent the evolutionarily most recent aspect of REM sleep, but more research with ectothermic vertebrates, such as fish, amphibians and reptiles, is needed before it can be concluded (as many prematurely have) that RBM is absent in these species. Evidence suggests a link between RBM sleep in early development and the clinical condition known as 'REM sleep behavior disorder (RBD)', which is characterized by the resurgence of periodic bouts of quasi-fetal motility that closely resemble RBM sleep. Early developmental neuromotor risk factors for RBD in humans also point to a relationship between RBM sleep and RBD.

  2. [The first film presentation of REM sleep behavior disorder precedes its scientific debut by 35 years].

    PubMed

    Janković, Slavko M; Sokić, Dragoslav V; Vojvodić, Nikola M; Ristić, Aleksandar J

    2006-01-01

    The perplexing and tantalizing disease of rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats. In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication, and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse. wever, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia. To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al [n 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep". Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene in a barn, clumsy and goofy dog Bruno is, as dogs

  3. [The first film presentation of REM sleep behavior disorder precedes its scientific debut by 35 years].

    PubMed

    Janković, Slavko M; Sokić, Dragoslav V; Vojvodić, Nikola M; Ristić, Aleksandar J

    2006-01-01

    The perplexing and tantalizing disease of rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by peculiar, potentially dangerous behavior during REM sleep. It was described both in animals and humans. RBD in mammals was first described by Jouvet and Delorme in 1965, based on an experimental model induced by lesion in pontine region of cats. In 1972, Passouant et al. described sleep with eye movements and persistent tonic muscle activity induced by tricyclic antidepressant medication, and Tachibana et al., in 1975, the preservation of muscle tone during REM sleep in the acute psychosis induced by alcohol and meprobamate abuse. wever, the first formal description of RBD in humans as new parasomnia was made by Schenck et al in 1986. Subsequently, in 1990, the International Classification of Sleep Disorders definitely recognized RBD as new parasomnia. To our knowledge, arts and literature do not mention RBD. Except for the quotation, made by Schenck et al [n 2002, of Don Quixote de la Mancha whose behavior in sleep strongly suggested that Miguel de Servantes actually described RBD, no other artistic work has portrayed this disorder. Only recently we become aware of the cinematic presentation of RBD which by decades precedes the first scientific description. The first presentation of RBD on film was made prior to the era of advanced electroencephalography and polysomnography, and even before the discovery of REM sleep by Aserinsky and Kleitman in 1953. The artistic and intuitive presentation of RBD was produced in Technicolor in a famous film "Cinderella" created by Walt Disney in 1950, some 35 years prior to its original publication in the journal "Sleep". Since there is an earlier version of the film initially produced in 1920, presumably containing this similar scene, we can only speculate that the first cinematic presentation of RBD might precede its scientific debut by 65 years. In a scene in a barn, clumsy and goofy dog Bruno is, as dogs

  4. GABAA receptor antagonism at the hypoglossal motor nucleus increases genioglossus muscle activity in NREM but not REM sleep.

    PubMed

    Morrison, Janna L; Sood, Sandeep; Liu, Hattie; Park, Eileen; Nolan, Philip; Horner, Richard L

    2003-04-15

    The pharyngeal muscles, such as the genioglossus (GG) muscle of the tongue, are important for effective lung ventilation since they maintain an open airspace. Rapid-eye-movement (REM) sleep, however, recruits powerful neural mechanisms that can abolish GG activity, even during strong reflex respiratory stimulation by elevated CO2. In vitro studies have demonstrated the presence of GABAA receptors on hypoglossal motoneurons, and these and other data have led to the speculation that GABAA mechanisms may contribute to the suppression of hypoglossal motor outflow to the GG muscle in REM sleep. We have developed an animal model that allows us to chronically manipulate neurotransmission at the hypoglossal motor nucleus using microdialysis across natural sleep-wake states in rats. The present study tests the hypothesis that microdialysis perfusion of the GABAA receptor antagonist bicuculline into the hypoglossal motor nucleus will prevent the suppression of GG muscle activity in REM sleep during both room-air and CO2-stimulated breathing. Ten rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and GG and diaphragm electrodes for respiratory muscle recording. Microdialysis probes were implanted into the hypoglossal motor nucleus for perfusion of artificial cerebrospinal fluid (ACSF) or 100 microM bicuculline during room-air and CO2-stimulated breathing (7 % inspired CO2). GABAA receptor antagonism at the hypoglossal motor nucleus increased respiratory-related GG activity during both room-air (P = 0.01) and CO2-stimulated breathing (P = 0.007), indicating a background inhibitory GABA tone. However, the effects of bicuculline on GG activity depended on the prevailing sleep-wake state (P < 0.005), with bicuculline increasing GG activity in non-REM (NREM) sleep and wakefulness both in room air and hypercapnia (P < 0.01), but GG activity was effectively abolished in those REM periods without phasic twitches in the GG muscle

  5. Circadian variation of EEG power spectra in NREM and REM sleep in humans: dissociation from body temperature

    NASA Technical Reports Server (NTRS)

    Dijk, D. J.

    1999-01-01

    In humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra - collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28-h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24-h period - was carried out. EEG power spectra were computed for NREM and REM sleep occurring between 90-120 and 270-300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the 'morning' and just after the 'evening' increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72 degrees C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed. The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.

  6. Overnight emotional adaptation to negative stimuli is altered by REM sleep deprivation and is correlated with intervening dream emotions.

    PubMed

    Lara-Carrasco, Jessica; Nielsen, Tore A; Solomonova, Elizaveta; Levrier, Katia; Popova, Ani

    2009-06-01

    Rapid eye movement (REM) sleep and dreaming may be implicated in cross-night adaptation to emotionally negative events. To evaluate the impact of REM sleep deprivation (REMD) and the presence of dream emotions on a possible emotional adaptation (EA) function, 35 healthy subjects randomly assigned to REMD (n = 17; mean age 26.4 +/- 4.3 years) and control (n = 18; mean age 23.7 +/- 4.4 years) groups underwent a partial REMD and control nights in the laboratory, respectively. In the evening preceding and morning following REMD, subjects rated neutral and negative pictures on scales of valence and arousal and EA scores were calculated. Subjects also rated dream emotions using the same scales and a 10-item emotions list. REMD was relatively successful in decreasing REM% on the experimental night, although a mean split procedure was applied to better differentiate subjects high and low in REM%. High and low groups differed - but in a direction contrary to expectations. Subjects high in REMD% showed greater adaptation to negative pictures on arousal ratings than did those low in REMD% (P < 0.05), even after statistically controlling sleep efficiency and awakening times. Subjects above the median on EA(valence) had less intense overall dream negativity (P < 0.005) and dream sadness (P < 0.004) than subjects below the median. A correlation between the emotional intensities of the morning dream and the morning picture ratings supports a possible emotional carry-over effect. REM sleep may enhance morning reactivity to negative emotional stimuli. Further, REM sleep and dreaming may be implicated in different dimensions of cross-night adaptation to negative emotions.

  7. Lithium affects REM sleep occurrence, autonomic activity and brain second messengers in the rat.

    PubMed

    Jones, Christine Ann; Perez, Emanuele; Amici, Roberto; Luppi, Marco; Baracchi, Francesca; Cerri, Matteo; Dentico, Daniela; Zamboni, Giovanni

    2008-03-01

    The effects of a single intraperitoneal administration of lithium, a drug used to prevent the recurrence of mania in bipolar disorders, were determined in the rat by studying changes in: (i) the wake-sleep cycle; (ii) autonomic parameters (hypothalamic and tail temperature, heart rate); (iii) the capacity to accumulate cAMP and IP(3) in the preoptic-anterior hypothalamic region (PO-AH) and in the cerebral cortex (CC) under an hypoxic stimulation at normal laboratory and at low ambient temperature (T(a)). In the immediate hours following the injection, lithium induced: (i) a significant reduction in REM sleep; (ii) a non-significant reduction in the delta power density of the EEG in NREM sleep; (iii) a significant decrease in the concentration of cAMP in PO-AH at normal laboratory T(a); (iv) a significant increase of IP(3) concentration in CC following exposure to low T(a). The earliest and most sensitive effects of lithium appear to be those concerning sleep. These changes are concomitant with biochemical effects that, in spite of a systemic administration of the substance, may be differentiated according to the second messenger involved, the brain region and the ambient condition.

  8. REM sleep deprivation generates cognitive and neurochemical disruptions in the intranigral rotenone model of Parkinson's disease.

    PubMed

    Dos Santos, Ana Carolina D; Castro, Marcela Alexandra V; Jose, Elis Angela K; Delattre, Ana Márcia; Dombrowski, Patrícia A; Da Cunha, Claudio; Ferraz, Anete C; Lima, Marcelo M S

    2013-11-01

    The recently described intranigral rotenone model of Parkinson's disease (PD) in rodents provides an interesting model for studying mechanisms of toxin-induced dopaminergic neuronal injury. The relevance of this model remains unexplored with regard to sleep disorders that occur in PD. On this basis, the construction of a PD model depicting several behavioral and neurochemical alterations related to sleep would be helpful in understanding the association between PD and sleep regulation. We performed bilateral intranigral injections of rotenone (12 μg) on day 0 and the open-field test initially on day 20 after rotenone. Acquisition phase of the object-recognition test, executed also during day 20, was followed by an exact period of 24 hr of rapid eye movement (REM) sleep deprivation (REMSD; day 21). In the subsequent day (22), the rats were re-exposed to the open-field test and to the object-recognition test (choice phase). After the last session of behavioral tests, the rat brains were immediately dissected, and their striata were collected for neurochemical purposes. We observed that a brief exposure to REMSD was able to impair drastically the object-recognition test, similarly to a nigrostriatal lesion promoted by intranigral rotenone. However, the combination of REMSD and rotenone surprisingly did not inflict memory impairment, concomitant with a moderate compensatory mechanism mediated by striatal dopamine release. In addition, we demonstrated the existence of changes in serotonin and noradrenaline neurotransmissions within the striatum mostly as a function of REMSD and REMSD plus rotenone, respectively.

  9. Medullary respiratory neural activity during hypoxia in NREM and REM sleep in the cat.

    PubMed

    Lovering, Andrew T; Fraigne, Jimmy J; Dunin-Barkowski, Witali L; Vidruk, Edward H; Orem, John M

    2006-02-01

    Intact unanesthetized cats hyperventilate in response to hypocapnic hypoxia in both wakefulness and sleep. This hyperventilation is caused by increases in diaphragmatic activity during inspiration and expiration. In this study, we recorded 120 medullary respiratory neurons during sleep in hypoxia. Our goal was to understand how these neurons change their activity to increase breathing efforts and frequency in response to hypoxia. We found that the response of medullary respiratory neurons to hypoxia was variable. While the activity of a small majority of inspiratory (58%) and expiratory (56%) neurons was increased in response to hypoxia, the activity of a small majority of preinspiratory (57%) neurons was decreased. Cells that were more active in hypoxia had discharge rates that averaged 183% (inspiratory decrementing), 154% (inspiratory augmenting), 155% (inspiratory), 230% (expiratory decrementing), 191% (expiratory augmenting), and 136% (expiratory) of the rates in normoxia. The response to hypoxia was similar in non-rapid-eye-movement (NREM) and REM sleep. Additionally, changes in the profile of activity were observed in all cell types examined. These changes included advanced, prolonged, and abbreviated patterns of activity in response to hypoxia; for example, some inspiratory neurons prolonged their discharge into expiration during the postinspiratory period in hypoxia but not in normoxia. Although changes in activity of the inspiratory neurons could account for the increased breathing efforts and activity of the diaphragm observed during hypoxia, the mechanisms responsible for the change in respiratory rate were not revealed by our data.

  10. The effects of leptin on REM sleep and slow wave delta in rats are reversed by food deprivation.

    PubMed

    Sinton, C M; Fitch, T E; Gershenfeld, H K

    1999-09-01

    Leptin (ob protein) is an adipose tissue derived circulating hormone that acts at specific receptors in the hypothalamus to reduce food intake. The protein is also critically involved in energy balance and metabolic status. Here the effect of leptin on sleep architecture in rats was evaluated because food consumption and metabolic status are known to influence sleep. Sprague-Dawley rats were chronically implanted with electrodes for EEG and EMG recording and diurnal sleep parameters were quantified over 9-h periods following leptin administration. Murine recombinant leptin (rMuLep) was administered systemically to rats that either had undergone 18 h of prior food deprivation or had received food ad libitum. In the normally fed rats, leptin significantly decreased the duration of rapid eye movement sleep (REMS) by about 30% and increased the duration of slow wave sleep (SWS) by about 13%, the latter effect reflecting enhanced power in the delta frequency band. These results are consistent with studies that have linked changes in metabolic rate with effects on sleep. Leptin administration has previously been shown to alter neuroendocrine parameters that could have mediated these changes in sleep architecture. Unexpectedly, prior food deprivation negated the effect of leptin on both REMS and SWS, a result that emphasizes the significance of the apparent coupling between sleep parameters and energy status.

  11. Paradoxical (REM) sleep genesis by the brainstem is under hypothalamic control.

    PubMed

    Luppi, Pierre-Hervé; Clément, Olivier; Fort, Patrice

    2013-10-01

    The purpose of this review is to outline our latest hypothesis on the mechanisms responsible for the genesis of paradoxical (REM) sleep (PS). On the basis of recent data, we propose that the onset and maintenance of PS are due to the activation by intrinsic and extrinsic factors of MCH/GABAergic neurons located in the lateral hypothalamic area. These neurons would inhibit during PS, GABAergic PS-off neurons located in the ventrolateral periaqueductal gray region. A number of results strongly suggest that these PS-off neurons gate the activation of the PS-on glutamatergic neurons located in the sublaterodorsal tegmental nucleus (SLD) and responsible for cortical activation and muscle atonia via descending projections to GABA/glycinergic neurons localized in the ventral medullary reticular nuclei.

  12. 5'-Ectonucleotidase-knockout mice lack non-REM sleep responses to sleep deprivation.

    PubMed

    Zielinski, Mark R; Taishi, Ping; Clinton, James M; Krueger, James M

    2012-06-01

    Adenosine and extracellular adenosine triphosphate (ATP) have multiple physiological central nervous system actions including regulation of cerebral blood flow, inflammation and sleep. However, their exact sleep regulatory mechanisms remain unknown. Extracellular ATP and adenosine diphosphate are converted to adenosine monophosphate (AMP) by the enzyme ectonucleoside triphosphate diphosphohydrolase 1, also known as CD39, and extracellular AMP is in turn converted to adenosine by the 5'-ectonuleotidase enzyme CD73. We investigated the role of CD73 in sleep regulation. Duration of spontaneous non-rapid eye movement sleep (NREMS) was greater in CD73-knockout (KO) mice than in C57BL/6 controls whether determined in our laboratory or by others. After sleep deprivation (SD), NREMS was enhanced in controls but not CD73-KO mice. Interleukin-1 beta (IL1β) enhanced NREMS in both strains, indicating that the CD73-KO mice were capable of sleep responses. Electroencephalographic power spectra during NREMS in the 1.0-2.5 Hz frequency range was significantly enhanced after SD in both CD73-KO and WT mice; the increases were significantly greater in the WT mice than in the CD73-KO mice. Rapid eye movement sleep did not differ between strains in any of the experimental conditions. With the exception of CD73 mRNA, the effects of SD on various adenosine-related mRNAs were small and similar in the two strains. These data suggest that sleep is regulated, in part, by extracellular adenosine derived from the actions of CD73.

  13. REM sleep behavior disorder and other sleep disturbances in Disney animated films.

    PubMed

    Iranzo, Alex; Schenck, Carlos H; Fonte, Jorge

    2007-08-01

    During a viewing of Disney's animated film Cinderella (1950), one author (AI) noticed a dog having nightmares with dream-enactment that strongly resembled RBD. This prompted a study in which all Disney classic full-length animated films and shorts were analyzed for other examples of RBD. Three additional dogs were found with presumed RBD in the classic films Lady and the Tramp (1955) and The Fox and the Hound (1981), and in the short Pluto's Judgment Day (1935). These dogs were elderly males who would pant, whine, snuffle, howl, laugh, paddle, kick, and propel themselves while dreaming that they were chasing someone or running away. In Lady and the Tramp the dog was also losing both his sense of smell and his memory, two associated features of human RBD. These four films were released before RBD was first formally described in humans and dogs. In addition, systematic viewing of the Disney films identified a broad range of sleep disorders, including nightmares, sleepwalking, sleep related seizures, disruptive snoring, excessive daytime sleepiness, insomnia and circadian rhythm sleep disorder. These sleep disorders were inserted as comic elements. The inclusion of a broad range of accurately depicted sleep disorders in these films indicates that the Disney screenwriters were astute observers of sleep and its disorders. PMID:17512793

  14. Acute nicotine treatment prevents REM sleep deprivation-induced learning and memory impairment in rat.

    PubMed

    Aleisa, A M; Helal, G; Alhaider, I A; Alzoubi, K H; Srivareerat, M; Tran, T T; Al-Rejaie, S S; Alkadhi, K A

    2011-08-01

    Rapid eye movement (REM) sleep deprivation (SD) is implicated in impairment of spatial learning and memory and hippocampal long-term potentiation (LTP). An increase in nicotine consumption among habitual smokers and initiation of tobacco use by nonsmokers was observed during SD. Although nicotine treatment was reported to attenuate the impairment of learning and memory and LTP associated with several mental disorders, the effect of nicotine on SD-induced learning and memory impairment has not been studied. Modified multiple platform paradigm was used to induce SD for 24 or 48 h during which rats were injected with saline or nicotine (1 mg kg(-1) s.c.) twice a day. In the radial arm water maze (RAWM) task, 24- or 48-h SD significantly impaired learning and short-term memory. In addition, extracellular recordings from CA1 and dentate gyrus (DG) regions of the hippocampus in urethane anesthetized rats showed a significant impairment of LTP after 24- and 48-h SD. Treatment of normal rats with nicotine for 24 or 48 h did not enhance spatial learning and memory or affect magnitude of LTP in the CA1 and DG regions. However, concurrent, acute treatment of rats with nicotine significantly attenuated SD-induced impairment of learning and STM and prevented SD-induced impairment of LTP in the CA1 and DG regions. These results show that acute nicotine treatment prevented the deleterious effect of sleep loss on cognitive abilities and synaptic plasticity.

  15. Mechanism of noradrenaline-induced stimulation of Na-K ATPase activity in the rat brain: implications on REM sleep deprivation-induced increase in brain excitability.

    PubMed

    Mallick, Birendra Nath; Singh, Sudhuman; Singh, Abhishek

    2010-03-01

    Rapid eye movement (REM) sleep is a unique phenomenon expressed in all higher forms of animals. Its quantity varies in different species and with ageing; it is also affected in several psycho-somatic disorders. Several lines of studies showed that after REM sleep loss, the levels of noradrenaline (NA) increase in the brain. The NA in the brain modulates neuronal Na-K ATPase activity, which helps maintaining the brain excitability status. The detailed mechanism of increase in NA level after REM sleep loss and the effect of NA on stimulation of Na-K ATPase in the neurons have been discussed. The findings have been reviewed and discussed with an aim to understand the role of REM sleep in maintaining brain excitability status.

  16. Trazodone Effects on Obstructive Sleep Apnea and Non-REM Arousal Threshold

    PubMed Central

    Edwards, Bradley A.; Deyoung, Pam N.; McSharry, David G.; Wellman, Andrew; Velasquez, Adrian; Owens, Robert; Orr, Jeremy E.; Malhotra, Atul

    2015-01-01

    Rationale: A low respiratory arousal threshold is a physiological trait involved in obstructive sleep apnea (OSA) pathogenesis. Trazodone may increase arousal threshold without compromising upper airway muscles, which should improve OSA. Objectives: We aimed to examine how trazodone alters OSA severity and arousal threshold. We hypothesized that trazodone would increase the arousal threshold and improve the apnea/hypopnea index (AHI) in selected patients with OSA. Methods: Subjects were studied on two separate nights in a randomized crossover design. Fifteen unselected subjects with OSA (AHI ≥ 10/h) underwent a standard polysomnogram plus an epiglottic catheter to measure the arousal threshold. Subjects were studied after receiving trazodone (100 mg) and placebo, with 1 week between conditions. The arousal threshold was calculated as the nadir pressure before electrocortical arousal from approximately 20 spontaneous respiratory events selected randomly. Measurements and Main Results: Compared with placebo, trazodone resulted in a significant reduction in AHI (38.7 vs. 28.5 events/h, P = 0.041), without worsening oxygen saturation or respiratory event duration. Trazodone was not associated with a significant change in the non-REM arousal threshold (−20.3 vs. −19.3 cm H2O, P = 0.51) compared with placebo. In subgroup analysis, responders to trazodone spent less time in N1 sleep (20.1% placebo vs. 9.0% trazodone, P = 0.052) and had an accompanying reduction in arousal index, whereas nonresponders were not observed to have a change in sleep parameters. Conclusions: These findings suggest that trazodone could be effective therapy for patients with OSA without worsening hypoxemia. Future studies should focus on underlying mechanisms and combination therapies to eliminate OSA. Clinical trial registered with www.clinicaltrials.gov (NCT 01817907). PMID:25719754

  17. REM sleep deprivation reverses neurochemical and other depressive-like alterations induced by olfactory bulbectomy.

    PubMed

    Maturana, Maira J; Pudell, Cláudia; Targa, Adriano D S; Rodrigues, Laís S; Noseda, Ana Carolina D; Fortes, Mariana H; Dos Santos, Patrícia; Da Cunha, Cláudio; Zanata, Sílvio M; Ferraz, Anete C; Lima, Marcelo M S

    2015-02-01

    There is compelling evidence that sleep deprivation (SD) is an effective strategy in promoting antidepressant effects in humans, whereas few studies were performed in relevant animal models of depression. Acute administration of antidepressants in humans and rats generates a quite similar effect, i.e., suppression of rapid eye movement (REM) sleep. Then, we decided to investigate the neurochemical alterations generated by a protocol of rapid eye movement sleep deprivation (REMSD) in the notably known animal model of depression induced by the bilateral olfactory bulbectomy (OBX). REMSD triggered antidepressant mechanisms such as the increment of brain-derived neurotrophic factor (BDNF) levels, within the substantia nigra pars compacta (SNpc), which were strongly correlated to the swimming time (r = 0.83; P < 0.0001) and hippocampal serotonin (5-HT) content (r = 0.66; P = 0.004). Moreover, there was a strong correlation between swimming time and hippocampal 5-HT levels (r = 0.70; P = 0.003), strengthen the notion of an antidepressant effect associated to REMSD in the OBX rats. In addition, REMSD robustly attenuated the hippocampal 5-HT deficiency produced by the OBX procedure. Regarding the rebound (REB) period, we observed the occurrence of a sustained antidepressant effect, indicated mainly by the swimming and climbing times which could be explained by the maintenance of the increased nigral BDNF expression. Hence, hippocampal 5-HT levels remained enhanced in the OBX group after this period. We suggested that the neurochemical complexity inflicted by the OBX model, counteracted by REMSD, is directly correlated to the nigral BDNF expression and hippocampal 5-HT levels. The present findings provide new information regarding the antidepressant mechanisms triggered by REMSD.

  18. How REM sleep deprivation and amantadine affects male rat sexual behavior.

    PubMed

    Ferraz, M R; Ferraz, M M; Santos, R

    2001-01-01

    There are conflicting findings about the sexual effects of REM sleep deprivation (REMd). Otherwise, several studies show a dopaminergic hypersensitivity after REMd. The effect of REMd and amantadine (AMA) was studied for standard measures and temporal patterning in the first experiment, in four groups: normal with vehicle, normal with AMA (5.0 and 10 mg/kg), REMd with vehicle and REMd with AMA (5.0 and 10.0 mg/kg). REMd reduced mount latency (ML), intromission latency (IL) and mount number (MN) and increased copulatory efficiency (CE) and hit rate factor. REMd also reduced the mount bout number (MBN) and increased the sexual interaction (mount bout time, MBT) among male and female during copula. AMA stimulates initiation and hit rate factors and accelerates the temporal patterning of sexual behavior, evoking fewer and quicker mount bouts. In the experiments with combination of REMd and AMA administration, AMA did not increase behavior effects evoked by REM deprivation, probably due to a top or a bottom effect, depending on the measures considered. A second experiment studied the effects of AMA (1.25 to 5.0 mg/kg) and REMd on the sexual reflexes of nonimmobilized male rats. REMd enhanced the AMA effects upon the seminal emission reflex, but inhibited the penile erection reflex elicited by 1.25 mg/kg of AMA. Curiously, our results showed that REMd, like AMA, a dopaminergic agonist, causes similar effects of sexual behavior in the male rat, particularly those related to arousal mechanism and hit rate factor. The results are discussed and the effects of REMd probably involve dopaminergic hypersensitivity and increased sexual motivational response.

  19. The coeruleus/subcoeruleus complex in idiopathic rapid eye movement sleep behaviour disorder.

    PubMed

    Ehrminger, Mickael; Latimier, Alice; Pyatigorskaya, Nadya; Garcia-Lorenzo, Daniel; Leu-Semenescu, Smaranda; Vidailhet, Marie; Lehericy, Stéphane; Arnulf, Isabelle

    2016-04-01

    Idiopathic rapid eye movement sleep behaviour disorder is characterized by nocturnal violence, increased muscle tone during rapid eye movement sleep and the lack of any other neurological disease. However, idiopathic rapid eye movement sleep behaviour disorder can precede parkinsonism and dementia by several years. Using 3 T magnetic resonance imaging and neuromelanin-sensitive sequences, we previously found that the signal intensity was reduced in the locus coeruleus/subcoeruleus area of patients with Parkinson's disease and rapid eye movement sleep behaviour disorder. Here, we studied the integrity of the locus coeruleus/subcoeruleus complex with neuromelanin-sensitive imaging in 21 patients with idiopathic rapid eye movement sleep behaviour disorder and compared the results with those from 21 age- and gender-matched healthy volunteers. All subjects underwent a clinical examination, motor, cognitive, autonomous, psychological, olfactory and colour vision tests, and rapid eye movement sleep characterization using video-polysomnography and 3 T magnetic resonance imaging. The patients more frequently had preclinical markers of alpha-synucleinopathies, including constipation, olfactory deficits, orthostatic hypotension, and subtle motor impairment. Using neuromelanin-sensitive imaging, reduced signal intensity was identified in the locus coeruleus/subcoeruleus complex of the patients with idiopathic rapid eye movement sleep behaviour. The mean sensitivity of the visual analyses of the signal performed by neuroradiologists who were blind to the clinical diagnoses was 82.5%, and the specificity was 81% for the identification of idiopathic rapid eye movement sleep behaviour. The results confirm that this complex is affected in idiopathic rapid eye movement sleep behaviour (to the same degree as it is affected in Parkinson's disease). Neuromelanin-sensitive imaging provides an early marker of non-dopaminergic alpha-synucleinopathy that can be detected on an individual

  20. The role of vestibular system and the cerebellum in adapting to gravitoinertial, spatial orientation and postural challenges of REM sleep.

    PubMed

    Dharani, Nataraj E

    2005-01-01

    The underlying reasons for, and mechanisms of rapid eye movement (REM) sleep events remain a mystery. The mystery has arisen from interpreting REM sleep events as occurring in 'isolation' from the world at large, and phylogenetically ancient brain areas using 'primal' gravity-dependent coordinates, reflexes and stimuli parameters to relay and process information about self and environment. This paper views REM sleep as a phylogenetically older form of wakefulness, wherein the brain uses a gravitoinertial-centred reference frame and an internal self-object model to evaluate and integrate inputs from several sensory systems and to adapt to spatial-temporal disintegration and malignant cholinergic-induced vasodepressor/ventilatory threat. The integration of vestibular and non-vestibular sensory graviceptor signals enables estimation and control of centre of the body mass, position and spatial relationship of body parts, gaze, head and whole-body tilt, spatial orientation and autonomic functions relative to gravity. The vestibulocerebellum and vermis, via vestibular and fastigial nucleus, coordinate inputs and outputs from several sensory systems and modulate the amplitude and duration of 'fight-or-flight' vestibulo-orienting and autonomic 'burst' responses to overcome the ongoing challenges. Resolving multisystem conflicts during the unique stresses (gravitoinertial, hypoxic, thermal, immobilisation, etc.) of REM sleep enables learning, cross-modal plasticity, higher-order integration and multidimensional spatial updating of sensory-motor-cognitive components. This paper aims to generate discussion, reinterpretation and creative testing of this novel hypothesis, which, if experimentally confirmed, has major implications across medicine, bioscience and space physiology, from developmental, clinical, research and theoretical perspectives.

  1. Effects of Chronic REM Sleep Restriction on D1 Receptor and Related Signal Pathways in Rat Prefrontal Cortex

    PubMed Central

    Han, Yan; Wen, Xiaosa; Rong, Fei; Chen, Xinmin; Ouyang, Ruying; Wu, Shuai; Nian, Hua; Ma, Wenling

    2015-01-01

    The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P < 0.01, P < 0.05); the expression of phosphor-PKAcα was significantly lowered in CSR rats (P < 0.05). The present results suggested that the alteration of neuropathology and D1R expression in PFC may be associated with CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function. PMID:25793215

  2. REM sleep deprivation promotes a dopaminergic influence in the striatal MT2 anxiolytic-like effects.

    PubMed

    Noseda, Ana Carolina D; Targa, Adriano D S; Rodrigues, Lais S; Aurich, Mariana F; Lima, Marcelo M S

    2016-01-01

    The aim of this study was to investigate the possible anxiolytic-like effects of striatal MT2 activation, and its counteraction induced by the selective blockade of this receptor. Furthermore, we analyzed this condition under the paradigm of rapid eye movement (REM) sleep deprivation (REMSD) and the animal model of Parkinson's disease (PD) induced by rotenone. Male Wistar rats were infused with intranigral rotenone (12 μg/μL), and 7 days later were subjected to 24 h of REMSD. Afterwards the rats underwent striatal micro-infusions of selective melatonin MT2 receptor agonist, 8-M-PDOT (10 μg/μL) or selective melatonin MT2 receptor antagonist, 4-P-PDOT (5 μg/μL) or vehicle. Subsequently, the animals were tested in the open-field (OP) and elevated plus maze (EPM) tests. Results indicated that the activation of MT2 receptors produced anxiolytic-like effects. In opposite, the MT2 blockade did not show an anxiogenic-like effect. Besides, REMSD induced anxiolytic-like effects similar to 8-M-PDOT. MT2 activation generated a prevalent locomotor increase compared to MT2 blockade in the context of REMSD. Together, these results suggest a striatal MT2 modulation associated to the REMSD-induced dopaminergic supersensitivity causing a possible dopaminergic influence in the MT2 anxiolytic-like effects in the intranigral rotenone model of PD.

  3. REM sleep deprivation promotes a dopaminergic influence in the striatal MT2 anxiolytic-like effects.

    PubMed

    Noseda, Ana Carolina D; Targa, Adriano D S; Rodrigues, Lais S; Aurich, Mariana F; Lima, Marcelo M S

    2016-01-01

    The aim of this study was to investigate the possible anxiolytic-like effects of striatal MT2 activation, and its counteraction induced by the selective blockade of this receptor. Furthermore, we analyzed this condition under the paradigm of rapid eye movement (REM) sleep deprivation (REMSD) and the animal model of Parkinson's disease (PD) induced by rotenone. Male Wistar rats were infused with intranigral rotenone (12 μg/μL), and 7 days later were subjected to 24 h of REMSD. Afterwards the rats underwent striatal micro-infusions of selective melatonin MT2 receptor agonist, 8-M-PDOT (10 μg/μL) or selective melatonin MT2 receptor antagonist, 4-P-PDOT (5 μg/μL) or vehicle. Subsequently, the animals were tested in the open-field (OP) and elevated plus maze (EPM) tests. Results indicated that the activation of MT2 receptors produced anxiolytic-like effects. In opposite, the MT2 blockade did not show an anxiogenic-like effect. Besides, REMSD induced anxiolytic-like effects similar to 8-M-PDOT. MT2 activation generated a prevalent locomotor increase compared to MT2 blockade in the context of REMSD. Together, these results suggest a striatal MT2 modulation associated to the REMSD-induced dopaminergic supersensitivity causing a possible dopaminergic influence in the MT2 anxiolytic-like effects in the intranigral rotenone model of PD. PMID:27226821

  4. REM sleep deprivation promotes a dopaminergic influence in the striatal MT2 anxiolytic-like effects

    PubMed Central

    Noseda, Ana Carolina D.; Targa, Adriano D.S.; Rodrigues, Lais S.; Aurich, Mariana F.; Lima, Marcelo M.S.

    2015-01-01

    The aim of this study was to investigate the possible anxiolytic-like effects of striatal MT2 activation, and its counteraction induced by the selective blockade of this receptor. Furthermore, we analyzed this condition under the paradigm of rapid eye movement (REM) sleep deprivation (REMSD) and the animal model of Parkinson’s disease (PD) induced by rotenone. Male Wistar rats were infused with intranigral rotenone (12 μg/μL), and 7 days later were subjected to 24 h of REMSD. Afterwards the rats underwent striatal micro-infusions of selective melatonin MT2 receptor agonist, 8-M-PDOT (10 μg/μL) or selective melatonin MT2 receptor antagonist, 4-P-PDOT (5 μg/μL) or vehicle. Subsequently, the animals were tested in the open-field (OP) and elevated plus maze (EPM) tests. Results indicated that the activation of MT2 receptors produced anxiolytic-like effects. In opposite, the MT2 blockade did not show an anxiogenic-like effect. Besides, REMSD induced anxiolytic-like effects similar to 8-M-PDOT. MT2 activation generated a prevalent locomotor increase compared to MT2 blockade in the context of REMSD. Together, these results suggest a striatal MT2 modulation associated to the REMSD-induced dopaminergic supersensitivity causing a possible dopaminergic influence in the MT2 anxiolytic-like effects in the intranigral rotenone model of PD. PMID:27226821

  5. High amplitude theta wave bursts: a novel electroencephalographic feature of rem sleep and cataplexy.

    PubMed

    Lo Martire, Viviana Carmen; Bastianini, Stefano; Berteotti, Chiara; Silvani, Alessandro; Zoccoli, Giovanna

    2015-01-01

    High amplitude theta wave bursts (HATs) were originally described during REMS and cataplexy in ORX-deficient mice as a novel neurophysiological correlate of narcolepsy (Bastianini et al., 2012). This finding was replicated the following year by Vassalli et al. in both ORX-deficient narcoleptic mice and narcoleptic children during cataplexy episodes (Vassalli et al., 2013). The relationship between HATs and narcolepsy-cataplexy in mice and patients indicates that the lack of ORX peptides is responsible for this abnormal EEG activity, the physiological meaning of which is still unknown. This review aimed to explore different phasic EEG events previously described in the published literature in order to find analogies and differences with HATs observed in narcoleptic mice and patients. We found similarities in terms of morphology, frequency and duration between HATs and several physiological (mu and wicket rhythms, sleep spindles, saw-tooth waves) or pathological (SWDs, HVSs, bursts of polyphasic complexes EEG complexes reported in a mouse model of CJD, and BSEs) EEG events. However, each of these events also shows significant differences from HATs, and thus cannot be equaled to them. The available evidence thus suggests that HATs are a novel neurophysiological phenomenon. Further investigations on HATs are required in order to investigate their physiological meaning, to individuate their brain structure(s) of origin, and to clarify the neural circuits involved in their manifestation. PMID:26742662

  6. Wheel running improves REM sleep and attenuates stress-induced flattening of diurnal rhythms in F344 rats.

    PubMed

    Thompson, Robert S; Roller, Rachel; Greenwood, Benjamin N; Fleshner, Monika

    2016-05-01

    Regular physical activity produces resistance to the negative health consequences of stressor exposure. One way that exercise may confer stress resistance is by reducing the impact of stress on diurnal rhythms and sleep; disruptions of which contribute to stress-related disease including mood disorders. Given the link between diurnal rhythm disruptions and stress-related disorders and that exercise both promotes stress resistance and is a powerful non-photic biological entrainment cue, we tested if wheel running could reduce stress-induced disruptions of sleep/wake behavior and diurnal rhythms. Adult, male F344 rats with or without access to running wheels were instrumented for biotelemetric recording of diurnal rhythms of locomotor activity, heart rate, core body temperature (CBT), and sleep (i.e. REM, NREM, and WAKE) in the presence of a 12 h light/dark cycle. Following 6 weeks of sedentary or exercise conditions, rats were exposed to an acute stressor known to disrupt diurnal rhythms and produce behaviors associated with mood disorders. Prior to stressor exposure, exercise rats had higher CBT, more locomotor activity during the dark cycle, and greater %REM during the light cycle relative to sedentary rats. NREM and REM sleep were consolidated immediately following peak running to a greater extent in exercise, compared to sedentary rats. In response to stressor exposure, exercise rats expressed higher stress-induced hyperthermia than sedentary rats. Stressor exposure disrupted diurnal rhythms in sedentary rats; and wheel running reduced these effects. Improvements in sleep and reduced diurnal rhythm disruptions following stress could contribute to the health promoting and stress protective effects of exercise. PMID:27124542

  7. Wheel running improves REM sleep and attenuates stress-induced flattening of diurnal rhythms in F344 rats.

    PubMed

    Thompson, Robert S; Roller, Rachel; Greenwood, Benjamin N; Fleshner, Monika

    2016-05-01

    Regular physical activity produces resistance to the negative health consequences of stressor exposure. One way that exercise may confer stress resistance is by reducing the impact of stress on diurnal rhythms and sleep; disruptions of which contribute to stress-related disease including mood disorders. Given the link between diurnal rhythm disruptions and stress-related disorders and that exercise both promotes stress resistance and is a powerful non-photic biological entrainment cue, we tested if wheel running could reduce stress-induced disruptions of sleep/wake behavior and diurnal rhythms. Adult, male F344 rats with or without access to running wheels were instrumented for biotelemetric recording of diurnal rhythms of locomotor activity, heart rate, core body temperature (CBT), and sleep (i.e. REM, NREM, and WAKE) in the presence of a 12 h light/dark cycle. Following 6 weeks of sedentary or exercise conditions, rats were exposed to an acute stressor known to disrupt diurnal rhythms and produce behaviors associated with mood disorders. Prior to stressor exposure, exercise rats had higher CBT, more locomotor activity during the dark cycle, and greater %REM during the light cycle relative to sedentary rats. NREM and REM sleep were consolidated immediately following peak running to a greater extent in exercise, compared to sedentary rats. In response to stressor exposure, exercise rats expressed higher stress-induced hyperthermia than sedentary rats. Stressor exposure disrupted diurnal rhythms in sedentary rats; and wheel running reduced these effects. Improvements in sleep and reduced diurnal rhythm disruptions following stress could contribute to the health promoting and stress protective effects of exercise.

  8. Motor disturbances during non-REM and REM sleep in narcolepsy-cataplexy: a video-polysomnographic analysis.

    PubMed

    Frauscher, Birgit; Gschliesser, Viola; Brandauer, Elisabeth; Schönwald, Suzana V; Falkenstetter, Tina; Ehrmann, Laura; Tokmak, Ismail; Poewe, Werner; Högl, Birgit

    2011-12-01

    Motor events during sleep can be frequently observed in patients with narcolepsy-cataplexy. We hypothesized that increased motor events and related arousals contribute to sleep fragmentation in this disease. We aimed to perform a detailed whole-night video-polysomnographic analysis of all motor events during non-rapid eye movement and rapid eye movement sleep in a group of narcolepsy-cataplexy patients and matched controls, and to assess the association with arousals. Video-polysomnographic registrations of six narcolepsy-cataplexy patients and six sex- and age-matched controls were analysed. Each motor event in the video was classified according to topography, number of involved body parts, duration and its association with arousals. The mean motor activity index was 59.9 ± 23.0 h(-1) in patients with narcolepsy-cataplexy compared with 15.4 ± 9.2 h(-1) in controls (P = 0.004). Distribution of motor events was similar in non-rapid eye movement and rapid eye movement sleep in the patient group (P = 0.219). In narcolepsy-cataplexy, motor events involved significantly more body parts (≥ 2 body regions: 38.2 ± 15.6 versus 14.9 ± 10.0; P = 0.011). In addition, the proportion of motor events lasting longer than 1 s was higher in patients than controls (88% versus 44.4%; P < 0.001). Both total and motor activity-related arousal indices were increased in narcolepsy-cataplexy (total arousal index: 21.6 ± 9.0 versus 8.7 ± 3.5; P = 0.004; motor activity-related arousal index: 17.6 ± 9.8 versus 5.9 ± 2.3; P = 0.002). Motor activity and motor activity-related arousal indices are increased in both non-rapid eye movement and rapid eye movement sleep in narcolepsy-cataplexy compared with controls. This supports the concept of a general sleep motor dysregulation in narcolepsy-cataplexy, which potentially contributes to or even underlies sleep fragmentation in this disease.

  9. Auditory responses and stimulus-specific adaptation in rat auditory cortex are preserved across NREM and REM sleep.

    PubMed

    Nir, Yuval; Vyazovskiy, Vladyslav V; Cirelli, Chiara; Banks, Matthew I; Tononi, Giulio

    2015-05-01

    Sleep entails a disconnection from the external environment. By and large, sensory stimuli do not trigger behavioral responses and are not consciously perceived as they usually are in wakefulness. Traditionally, sleep disconnection was ascribed to a thalamic "gate," which would prevent signal propagation along ascending sensory pathways to primary cortical areas. Here, we compared single-unit and LFP responses in core auditory cortex as freely moving rats spontaneously switched between wakefulness and sleep states. Despite robust differences in baseline neuronal activity, both the selectivity and the magnitude of auditory-evoked responses were comparable across wakefulness, Nonrapid eye movement (NREM) and rapid eye movement (REM) sleep (pairwise differences <8% between states). The processing of deviant tones was also compared in sleep and wakefulness using an oddball paradigm. Robust stimulus-specific adaptation (SSA) was observed following the onset of repetitive tones, and the strength of SSA effects (13-20%) was comparable across vigilance states. Thus, responses in core auditory cortex are preserved across sleep states, suggesting that evoked activity in primary sensory cortices is driven by external physical stimuli with little modulation by vigilance state. We suggest that sensory disconnection during sleep occurs at a stage later than primary sensory areas.

  10. Dorsolateral prefrontal transcranial magnetic stimulation in patients with major depression locally affects alpha power of REM sleep

    PubMed Central

    Pellicciari, Maria Concetta; Cordone, Susanna; Marzano, Cristina; Bignotti, Stefano; Gazzoli, Anna; Miniussi, Carlo; De Gennaro, Luigi

    2013-01-01

    Sleep alterations are among the most important disabling manifestation symptoms of Major Depression Disorder (MDD). A critical role of sleep importance is also underlined by the fact that its adjustment has been proposed as an objective marker of clinical remission in MDD. Repetitive transcranial magnetic stimulation (rTMS) represents a relatively novel therapeutic tool for the treatment of drug-resistant depression. Nevertheless, besides clinical evaluation of the mood improvement after rTMS, we have no clear understanding of what are the neurophysiological correlates of such treatment. One possible marker underlying the clinical outcome of rTMS in MDD could be cortical changes on wakefulness and sleep activity. The aim of this open-label study was to evaluate the efficacy of a sequential bilateral rTMS treatment over the dorsolateral prefrontal cortex (DLPFC) to improve the mood in MDD patients, and to determine if rTMS can induce changes on the sleep structure, and if those changes can be used as a surrogate marker of the clinical state of the patient. Ten drug-resistant depressed patients participated to ten daily sessions of sequential bilateral rTMS with a low-frequency TMS (1 Hz) over right-DLPFC and a subsequent high-frequency (10 Hz) TMS over left-DLPFC. The clinical and neurophysiological effects induced by rTMS were evaluated, respectively by means of the Hamilton Depression Rating Scale (HDRS), and by comparing the sleep pattern modulations and the spatial changes of EEG frequency bands during both NREM and REM sleep, before and after the real rTMS treatment. The sequential bilateral rTMS treatment over the DLPFC induced topographical-specific decrease of the alpha activity during REM sleep over left-DLPFC, which is significantly associated to the clinical outcome. In line with the notion of a left frontal hypoactivation in MDD patients, the observed local decrease of alpha activity after rTMS treatment during the REM sleep suggests that alpha frequency

  11. The serotonin 5-HT7 receptor agonist LP-44 microinjected into the dorsal raphe nucleus suppresses REM sleep in the rat.

    PubMed

    Monti, Jaime M; Leopoldo, Marcello; Jantos, Héctor

    2008-08-22

    The effects of LP-44, a selective 5-HT7 receptor agonist, and of SB-269970, a selective 5-HT7 receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The 5-HT7 receptor ligands were microinjected directly into the dorsal raphe nucleus (DRN) during the light period of the 12-h light/12-h dark cycle. Infusion of LP-44 (1.25-5.0 mM) into the DRN induced a significant reduction of rapid-eye-movement sleep (REMS) and of the number of REM periods. Similar effects were observed after the direct administration into the DRN of SB-269970 (0.5-1.0 mM). Pretreatment with a dose of SB-269970 (0.5 mM) that significantly affects sleep variables antagonized the LP-44 (2.5 mM)-induced suppression of REMS and of the number of REM periods. It is proposed that the suppression of REMS after microinjection of LP-44 into the DRN is related, at least in part, to the activation of GABAergic neurons in the DRN that contribute to long projections that reach, among others, the laterodorsal and pedunculopontine tegmental nuclei involved in the promotion of REMS.

  12. Inhibition of A5 Neurons Facilitates the Occurrence of REM Sleep-Like Episodes in Urethane-Anesthetized Rats: A New Role for Noradrenergic A5 Neurons?

    PubMed

    Fenik, Victor B; Marchenko, Vitaliy; Davies, Richard O; Kubin, Leszek

    2012-01-01

    When rapid eye movement (REM) sleep occurs, noradrenergic cells become silent, with the abolition of activity in locus coeruleus (LC) neurons seen as a key event permissive for the occurrence of REM sleep. However, it is not known whether silencing of other than LC noradrenergic neurons contributes to the generation of REM sleep. In urethane-anesthetized rats, stereotyped REM sleep-like episodes can be repeatedly elicited by injections of the cholinergic agonist, carbachol, into a discrete region of the dorsomedial pons. We used this preparation to test whether inhibition of ventrolateral pontine noradrenergic A5 neurons only, or together with LC neurons, also can elicit REM sleep-like effects. To silence noradrenergic cells, we sequentially injected the α(2)-adrenergic agonist clonidine (20-40 nl, 0.75 mM) into both A5 regions and then the LC. In two rats, successful bilateral clonidine injections into the A5 region elicited the characteristic REM sleep-like episodes (hippocampal theta rhythm, suppression of hypoglossal nerve activity, reduced respiratory rate). In five rats, bilateral clonidine injections into the A5 region and then into one LC triggered REM sleep-like episodes, and in two rats injections into both A5 and then both LC were needed to elicit the effect. In contrast, in three rats, uni- or bilateral clonidine injections only into the LC had no effect, and clonidine injections placed in another six rats outside of the A5 and/or LC regions were without effect. The REM sleep-like episodes elicited by clonidine had similar magnitude of suppression of hypoglossal nerve activity (by 75%), similar pattern of hippocampal changes, and similar durations (2.5-5.3 min) to the episodes triggered in the same preparation by carbachol injections into the dorsomedial pontine reticular formation. Thus, silencing of A5 cells may importantly enable the occurrence of REM sleep-like episodes, at least under anesthesia. This is a new role for noradrenergic A5

  13. Inhibition of A5 Neurons Facilitates the Occurrence of REM Sleep-Like Episodes in Urethane-Anesthetized Rats: A New Role for Noradrenergic A5 Neurons?

    PubMed Central

    Fenik, Victor B.; Marchenko, Vitaliy; Davies, Richard O.; Kubin, Leszek

    2012-01-01

    When rapid eye movement (REM) sleep occurs, noradrenergic cells become silent, with the abolition of activity in locus coeruleus (LC) neurons seen as a key event permissive for the occurrence of REM sleep. However, it is not known whether silencing of other than LC noradrenergic neurons contributes to the generation of REM sleep. In urethane-anesthetized rats, stereotyped REM sleep-like episodes can be repeatedly elicited by injections of the cholinergic agonist, carbachol, into a discrete region of the dorsomedial pons. We used this preparation to test whether inhibition of ventrolateral pontine noradrenergic A5 neurons only, or together with LC neurons, also can elicit REM sleep-like effects. To silence noradrenergic cells, we sequentially injected the α2-adrenergic agonist clonidine (20–40 nl, 0.75 mM) into both A5 regions and then the LC. In two rats, successful bilateral clonidine injections into the A5 region elicited the characteristic REM sleep-like episodes (hippocampal theta rhythm, suppression of hypoglossal nerve activity, reduced respiratory rate). In five rats, bilateral clonidine injections into the A5 region and then into one LC triggered REM sleep-like episodes, and in two rats injections into both A5 and then both LC were needed to elicit the effect. In contrast, in three rats, uni- or bilateral clonidine injections only into the LC had no effect, and clonidine injections placed in another six rats outside of the A5 and/or LC regions were without effect. The REM sleep-like episodes elicited by clonidine had similar magnitude of suppression of hypoglossal nerve activity (by 75%), similar pattern of hippocampal changes, and similar durations (2.5–5.3 min) to the episodes triggered in the same preparation by carbachol injections into the dorsomedial pontine reticular formation. Thus, silencing of A5 cells may importantly enable the occurrence of REM sleep-like episodes, at least under anesthesia. This is a new role for noradrenergic A5

  14. Spatiotemporal structure of REM sleep twitching reveals developmental origins of motor synergies

    PubMed Central

    Blumberg, Mark S.; Coleman, Cassandra M.; Gerth, Ashlynn I.; McMurray, Bob

    2013-01-01

    Summary Background During active (or REM) sleep, infant rats and other mammals exhibit myoclonic twitches of skeletal muscles throughout the body, resulting in jerky, discrete movements of the distal limbs. Hundreds of thousands of limb twitches are produced each day and sensory feedback from these movements is a substantial driver of infant brain activity, suggesting that these movements contribute to motor learning and sensorimotor integration. However, it is not known whether the production of twitches is random or spatiotemporally structured, or whether the patterning of twitching changes with age. Such information is critical if we are to understand how twitches contribute to development. Results We used high-speed videography and 3-D motion tracking to assess the spatiotemporal structure of twitching at forelimb joints in 2- and 8-day-old rats. At both ages, twitches exhibited highly structured spatiotemporal properties at multiple timescales, including synergistic and multi-joint movements within and across forelimbs. Hierarchical cluster analysis and latent class analysis revealed developmental changes in the quantity and patterning of twitching. Critically, we found evidence for a selectionist process whereby movement patterns at the early age compete for retention and expression over development. Conclusions These findings indicate that twitches are not produced randomly, but rather are highly structured at multiple timescales. This structure has important implications for our understanding of the brain and spinal mechanisms that produce twitching and the role that sensory feedback from twitching plays in the development of sensorimotor systems. We suggest that twitches represent a heretofore overlooked form of motor exploration that helps animals probe the biomechanics of their limbs, build motor synergies, and lay a foundation for complex, automatic, and goal-directed wake movements. PMID:24139739

  15. Neural Correlates of Dream Lucidity Obtained from Contrasting Lucid versus Non-Lucid REM Sleep: A Combined EEG/fMRI Case Study

    PubMed Central

    Dresler, Martin; Wehrle, Renate; Spoormaker, Victor I.; Koch, Stefan P.; Holsboer, Florian; Steiger, Axel; Obrig, Hellmuth; Sämann, Philipp G.; Czisch, Michael

    2012-01-01

    Study Objectives: To investigate the neural correlates of lucid dreaming. Design: Parallel EEG/fMRI recordings of night sleep. Setting: Sleep laboratory and fMRI facilities. Participants: Four experienced lucid dreamers. Interventions: N/A. Measurements and Results: Out of 4 participants, one subject had 2 episodes of verified lucid REM sleep of sufficient length to be analyzed by fMRI. During lucid dreaming the bilateral precuneus, cuneus, parietal lobules, and prefrontal and occipito-temporal cortices activated strongly as compared with non-lucid REM sleep. Conclusions: In line with recent EEG data, lucid dreaming was associated with a reactivation of areas which are normally deactivated during REM sleep. This pattern of activity can explain the recovery of reflective cognitive capabilities that are the hallmark of lucid dreaming. Citation: Dresler M; Wehrle R; Spoormaker VI; Koch SP; Holsboer F; Steiger A; Obrig H; Sämann PG; Czisch M. Neural correlates of dream lucidity obtained from contrasting lucid versus non-lucid REM sleep: a combined EEG/fMRI case study. SLEEP 2012;35(7):1017–1020. PMID:22754049

  16. Hypocretinergic and non-hypocretinergic projections from the hypothalamus to the REM sleep executive area of the pons.

    PubMed

    Torterolo, Pablo; Sampogna, Sharon; Chase, Michael H

    2013-01-23

    Within the postero-lateral hypothalamus neurons that utilize hypocretin or melanin-concentrating hormone (MCH) as neuromodulators are co-distributed. These neurons have been involved in the control of behavioral states, and a deficit in the hypocretinergic system is the pathogenic basis of narcolepsy with cataplexy. In this report, utilizing immunohistochemistry and retrograde tracing techniques, we examined the hypocretinergic innervation of the nucleus pontis oralis (NPO), which is the executive site that is responsible for the generation of REM sleep in the cat. The retrograde tracer cholera toxin subunit b (CTb) was administered in pontine regions where carbachol microinjections induced REM sleep. Utilizing immunohistochemical techniques, we found that approximately 1% of hypocretinergic neurons in the tuberal area of the hypothalamus project to the NPO. In addition, approximately 6% of all CTb+ neurons in this region were hypocretinergic. The hypocretinergic innervation of the NPO was also compared with the innervation of the same site by MCH-containing neurons. More than three times as many MCHergic neurons were found to project to the NPO compared with hypocretinergic cells; both neuronal types exhibited bilateral projections. We also identified a group of non-hypocretinergic non-MCHergic neuronal group of neurons that were intermingled with both hypocretinergic and MCHergic neurons that also projected to this same brainstem region. These neurons were grater in number that either hypocretin or MCH-containing neurons; their soma size was also smaller and their projections were mainly ipsilateral. The present anatomical data suggest that hypocretinergic, MCHergic and an unidentified companion group of neurons of the postero-lateral hypothalamus participate in the regulation of the neuronal activity of NPO neurons, and therefore, are likely to participate in the control of wakefulness and REM sleep. PMID:23122879

  17. Hypocretinergic and non-hypocretinergic projections from the hypothalamus to the REM sleep executive area of the pons.

    PubMed

    Torterolo, Pablo; Sampogna, Sharon; Chase, Michael H

    2013-01-23

    Within the postero-lateral hypothalamus neurons that utilize hypocretin or melanin-concentrating hormone (MCH) as neuromodulators are co-distributed. These neurons have been involved in the control of behavioral states, and a deficit in the hypocretinergic system is the pathogenic basis of narcolepsy with cataplexy. In this report, utilizing immunohistochemistry and retrograde tracing techniques, we examined the hypocretinergic innervation of the nucleus pontis oralis (NPO), which is the executive site that is responsible for the generation of REM sleep in the cat. The retrograde tracer cholera toxin subunit b (CTb) was administered in pontine regions where carbachol microinjections induced REM sleep. Utilizing immunohistochemical techniques, we found that approximately 1% of hypocretinergic neurons in the tuberal area of the hypothalamus project to the NPO. In addition, approximately 6% of all CTb+ neurons in this region were hypocretinergic. The hypocretinergic innervation of the NPO was also compared with the innervation of the same site by MCH-containing neurons. More than three times as many MCHergic neurons were found to project to the NPO compared with hypocretinergic cells; both neuronal types exhibited bilateral projections. We also identified a group of non-hypocretinergic non-MCHergic neuronal group of neurons that were intermingled with both hypocretinergic and MCHergic neurons that also projected to this same brainstem region. These neurons were grater in number that either hypocretin or MCH-containing neurons; their soma size was also smaller and their projections were mainly ipsilateral. The present anatomical data suggest that hypocretinergic, MCHergic and an unidentified companion group of neurons of the postero-lateral hypothalamus participate in the regulation of the neuronal activity of NPO neurons, and therefore, are likely to participate in the control of wakefulness and REM sleep.

  18. Principal component structuring of the non-REM Sleep EEG spectrum in older adults yields age-related changes in the sleep and wake drives.

    PubMed

    Putilov, Arcady A; Münch, Mirjam Y; Cajochen, Christian

    2013-12-01

    Age-related disturbances of the sleep-wake cycle can reflect ontogenetic changes in regulatory mechanisms underlying normal and pathological aging, but the exact nature of these changes remains unclear. The present report is the first attempt to apply principal component analysis to the electroencephalographic (EEG) spectrum to examine of whether the observed age-related changes in the objective sleep measures can be linked to the opponent sleep-promoting and wake-promoting processes. The EEG indicators of these processes--scores on the 1st and 2nd principal components of the EEG spectrum, respectively--were compared in 15 older (57-74 years) and 16 younger (20-31 years) healthy volunteers. The scores were calculated for non-REM sleep episodes which occurred during ten 75-min naps scheduled every 150 min throughout a 40-h constant routine protocol. Both, a decrease of the 1st principal component score and an increase of the 2nd principal component score were found to contribute to such most obvious age-related modification of the sleep EEG spectrum as attenuation of EEG slow-wave activity in older people. Therefore, we concluded that the normal aging process can reflect both a weakening of the sleep-promoting process and a strengthening of the wake-promoting process, respectively. Such bidirectional changes in chronoregulatory processes may explain why sleep of older people is characterized by the few profitable and a number of detrimental features (i.e., a better ability to cope with daytime sleepiness and sleep loss vs. difficulty of falling asleep, decreased total nighttime sleep, "lightened" and fragmentized sleep, unwanted early morning awakenings, etc.).

  19. Induction of active (REM) sleep and motor inhibition by hypocretin in the nucleus pontis oralis of the cat.

    PubMed

    Xi, Ming-Chu; Fung, Simon J; Yamuy, Jack; Morales, Francisco R; Chase, Michael H

    2002-06-01

    Hypocretin (orexin)-containing neurons in the hypothalamus, which have been implicated in the pathology of narcolepsy, project to nuclei in the brain stem reticular formation that are involved in the control of the behavioral states of sleep and wakefulness. Among these nuclei is the nucleus pontis oralis (NPO). Consequently, the present study was undertaken to determine if the hypocretinergic system provides regulatory input to neurons in the NPO with respect to the generation of the states of sleep and wakefulness. Accordingly, polygraphic recordings and behavioral observations were obtained before and after hypocretin-1 and -2 were microinjected into the NPO in chronic, unanesthetized cats. Microinjections of either hypocretin-1 or -2 elicited, with a short latency, a state of active [rapid eye movement (REM)] sleep that appeared identical to naturally occurring active sleep. The percentage of time spent in active sleep was significantly increased. Dissociated states, which are characterized by the presence of muscle atonia without one or more of the electrophysiological correlates of active sleep, also arose following the injection. The effect of juxtacellular application of hypocretin-1 on the electrical activity of intracellularly recorded NPO neurons was then examined in the anesthetized cat. In this preparation, the application of hypocretin-1 resulted in the depolarization of NPO neurons, an increase in the frequency of their discharge and an increase in their excitability. These latter data represent the first description of the in vivo action of hypocretin on intracellularly recorded neuronal activity and provide evidence that the active sleep-inducing effects of hypocretin are due to a direct excitatory action on NPO neurons. Therefore we suggest that hypocretinergic processes in the NPO may play a role in the generation of active sleep, particularly muscle atonia and therefore are likely to be involved in the pathology of narcolepsy. PMID:12037191

  20. Up-regulated neuronal COX-2 expression after cortical spreading depression is involved in non-REM sleep induction in rats.

    PubMed

    Cui, Yilong; Kataoka, Yosky; Inui, Takashi; Mochizuki, Takatoshi; Onoe, Hirotaka; Matsumura, Kiyoshi; Urade, Yoshihiro; Yamada, Hisao; Watanabe, Yasuyoshi

    2008-03-01

    Cortical spreading depression is an excitatory wave of depolarization spreading throughout cerebral cortex at a rate of 2-5 mm/min and has been implicated in various neurological disorders, such as epilepsy, migraine aura, and trauma. Although sleepiness or sleep is often induced by these neurological disorders, the cellular and molecular mechanism has remained unclear. To investigate whether and how the sleep-wake behavior is altered by such aberrant brain activity, we induced cortical spreading depression in freely moving rats, monitoring REM and non-REM (NREM) sleep and sleep-associated changes in cyclooxygenase (COX)-2 and prostaglandins (PGs). In such a model for aberrant neuronal excitation in the cerebral cortex, the amount of NREM sleep, but not of REM sleep, increased subsequently for several hours, with an up-regulated expression of COX-2 in cortical neurons and considerable production of PGs. A specific inhibitor of COX-2 completely arrested the increase in NREM sleep. These results indicate that up-regulated neuronal COX-2 would be involved in aberrant brain excitation-induced NREM sleep via production of PGs.

  1. Percentage of REM sleep is associated with overnight change in leptin.

    PubMed

    Olson, Christy A; Hamilton, Nancy A; Somers, Virend K

    2016-08-01

    Sleep contributes importantly to energy homeostasis, and may impact hormones regulating appetite, such as leptin, an adipocyte-derived hormone. There is increasing evidence that sleep duration, and reduced rapid eye movement sleep, are linked to obesity. Leptin has central neural effects beyond modulation of appetite alone. As sleep is not a unifrom process, interactions between leptin and sleep stages including rapid eye movement sleep may play a role in the relationship between sleep and obesity. This study examined the relationship between serum leptin and rapid eye movement sleep in a sample of healthy adults. Participants were 58 healthy adults who underwent polysomnography. Leptin was measured before and after sleep. It was hypothesized that a lower percentage of rapid eye movement sleep would be related to lower leptin levels during sleep. The relationship between percentage of rapid eye movement sleep and leptin was analysed using hierarchical linear regression. An increased percentage of rapid eye movement sleep was related to a greater reduction in leptin during sleep even when controlling for age, gender, percent body fat and total sleep time. A greater percentage of rapid eye movement sleep was accompanied by more marked reductions in leptin. Studies examining the effects of selective rapid eye movement sleep deprivation on leptin levels, and hence on energy homeostasis in humans, are needed. PMID:26919408

  2. I know how you felt last night, or do I? Self- and external ratings of emotions in REM sleep dreams.

    PubMed

    Sikka, Pilleriin; Valli, Katja; Virta, Tiina; Revonsuo, Antti

    2014-04-01

    We investigated whether inconsistencies in previous studies regarding emotional experiences in dreams derive from whether dream emotions are self-rated or externally evaluated. Seventeen subjects were monitored with polysomnography in the sleep laboratory and awakened from every rapid eye movement (REM) sleep stage 5 min after the onset of the stage. Upon awakening, participants gave an oral dream report and rated their dream emotions using the modified Differential Emotions Scale, whereas external judges rated the participants' emotions expressed in the dream reports, using the same scale. The two approaches produced diverging results. Self-ratings, as compared to external ratings, resulted in greater estimates of (a) emotional dreams; (b) positively valenced dreams; (c) positive and negative emotions per dream; and (d) various discrete emotions represented in dreams. The results suggest that this is mostly due to the underrepresentation of positive emotions in dream reports. Possible reasons for this discrepancy are discussed.

  3. Postural sway in idiopathic rapid eye movement sleep behavior disorder: a potential marker of prodromal Parkinson's disease.

    PubMed

    Chen, Tuan-Zhi; Xu, Guang-Jun; Zhou, Guang-An; Wang, Jing-Ru; Chan, Piu; Du, Yi-Feng

    2014-04-22

    There is compelling evidence that postural instability occurs at very early clinical stages of Parkinson's disease (PD), making it tempting to speculate that changes in postural sway may even occur at a prodromal phase. Studies estimate that approximately half of patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) will eventually develop PD, so RBD may be an indicator of prodromal PD. This study was undertaken to investigate postural sway and its relation to stereopsis function in patients with RBD. We examined 24 patients with polysomnography-confirmed RBD and 23 healthy, sex-and age-matched control subjects. Postural sway was measured with an accelerometer at the center of mass at the lower spine. Subjects were asked to stand quietly for 30s under two usual conditions (eyes open and eyes closed) and three challenging conditions (eyes open with dual task, eyes closed with dual task, and tandem standing). Stereopsis was assessed using the Titmus fly test. RBD patients showed an increased variability of trunk acceleration and a decrease of smoothness of sway, compared to control subjects. These differences reached significance in the challenging conditions. RBD patients demonstrated significant impairment in stereopsis. There were statistically significant correlations between log seconds of arc of the Titmus test and some sway parameters within the RBD group. RBD patients with abnormal stereopsis showed a significant increase of JERK values compared to patients with normal stereopsis in the challenging conditions. Our results indicate that idiopathic RBD patients, especially with abnormal stereopsis, have subtle signs of postural instability under challenging conditions. Postural sway performance may serve as a biological marker for prodromal PD.

  4. Not only … but also: REM sleep creates and NREM Stage 2 instantiates landmark junctions in cortical memory networks.

    PubMed

    Llewellyn, Sue; Hobson, J Allan

    2015-07-01

    This article argues both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep contribute to overnight episodic memory processes but their roles differ. Episodic memory may have evolved from memory for spatial navigation in animals and humans. Equally, mnemonic navigation in world and mental space may rely on fundamentally equivalent processes. Consequently, the basic spatial network characteristics of pathways which meet at omnidirectional nodes or junctions may be conserved in episodic brain networks. A pathway is formally identified with the unidirectional, sequential phases of an episodic memory. In contrast, the function of omnidirectional junctions is not well understood. In evolutionary terms, both animals and early humans undertook tours to a series of landmark junctions, to take advantage of resources (food, water and shelter), whilst trying to avoid predators. Such tours required memory for emotionally significant landmark resource-place-danger associations and the spatial relationships amongst these landmarks. In consequence, these tours may have driven the evolution of both spatial and episodic memory. The environment is dynamic. Resource-place associations are liable to shift and new resource-rich landmarks may be discovered, these changes may require re-wiring in neural networks. To realise these changes, REM may perform an associative, emotional encoding function between memory networks, engendering an omnidirectional landmark junction which is instantiated in the cortex during NREM Stage 2. In sum, REM may preplay associated elements of past episodes (rather than replay individual episodes), to engender an unconscious representation which can be used by the animal on approach to a landmark junction in wake. PMID:25921620

  5. REM sleep deprivation-induced noradrenaline stimulates neuronal and inhibits glial Na-K ATPase in rat brain: in vivo and in vitro studies.

    PubMed

    Baskey, Ganesh; Singh, Abhishek; Sharma, Rakhi; Mallick, Birendra Nath

    2009-01-01

    Increased noradrenaline, induced by rapid eye movement (REM) sleep deprivation, stimulates Na-K ATPase activity in the rat brain. The brain contains neurons as well as glia and both possess Na-K ATPase, however, it was not known if REM sleep deprivation affects the enzyme in both types of cells identically. Rats were REM sleep deprived by the flowerpot method and free moving, large platform and recovery controls were carried out. Na-K ATPase activity was measured in membranes prepared from whole brain as well as from neuronal and glial fractions separated from REM sleep-deprived and control rats. The effects of noradrenaline (NA) in different fractions were studied with or without in vivo i.p. treatment of prazosin, an alpha1-adrenpceptor antagonist, as well as in vitro membranes prepared from neurons and glia separated from normal rat brain. Further, to confirm the findings, membranes were prepared from neuro2a and C6 cell lines treated with NA in the presence and absence of prazosin and Na-K ATPase activity was estimated. The results showed that neuron and neuro2a as well as glia and C6 possess comparable Na-K ATPase activity. After REM sleep deprivation the neuronal Na-K ATPase activity increased, while the glial enzyme activity decreased and these changes were mediated by NA acting on alpha1-adrenoceptor; comparable results were obtained by treating the neuro2a and C6 cell lines with NA. The opposite actions of NA on neuronal and glial Na-K ATPase activity probably help maintain neuronal homeostasis.

  6. Sleep problems and associated factors in children with juvenile idiopathic arthritis: a systematic review

    PubMed Central

    2014-01-01

    Background Sleep problems are common among children with chronic illnesses such as Juvenile Idiopathic Arthritis (or JIA). However, little is known about the frequency and severity of sleep disturbance(s) and the factors that are associated with sleep problems in children with JIA. The mechanism(s) of the relationships characterizing the development or exacerbation of sleep problems in children with JIA are still unknown, however studies have reported an association. The purpose of this study was to synthesize existing research related to sleep problems in children with JIA. Methods The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement guided the conduct and reporting of this review. An experienced librarian conducted searches in MEDLINE, EMBASE, PsychINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to January 2012, to identify potentially relevant citations. Two members independently selected, rated methodological quality using the QUIPS tool, and extracted data from included studies. Results Ten studies were included and findings varied across studies; studies were mostly cross-sectional, or case-controlled designs, with only one cohort study available. Four studies found that children and adolescents diagnosed with JIA had significantly more sleep disturbances when compared to healthy controls. Pain was most often associated with sleep disturbances. The heterogeneous findings highlight the complex relationships between JIA and sleep, and low methodological quality of studies in the field. Conclusions This review supports an association between poor sleep and increased symptoms related to JIA, specifically the experience of pain. However, results need to be interpreted cautiously given the inconsistent findings regarding factors associated with sleep problems in JIA, the limited evidence available, and its low quality. Furthermore it is not yet determined if the poor sleep patterns predate the

  7. Increases in number of REMS and REM density in humans following an intensive learning period.

    PubMed

    Smith, C; Lapp, L

    1991-08-01

    Animal studies have recently demonstrated that increases in rapid eye movement (REM) sleep and actual number of rapid eye movements (REMs) over normal levels followed successful learning of an avoidance task. These increases persisted for many days following the end of the training sessions. It was hypothesized that similar extended increases in REM sleep parameters would follow an intensive learning task in humans. Senior college students were sleep monitored following the end of their Christmas examinations. Results showed that there was a significant increase in the number of REMs observed following the exams as compared to baseline and control subject values. The number of extra REMs was mot prominent during the fifth REM period of the night. A significantly increased REM density was observed at the fourth REM sleep period of the night. Results support the idea of REM sleep and/or the REMs themselves being involved in long-term memory processing several days after the end of training.

  8. Slow wave and rem sleep mechanisms are differently altered in hereditary pick disease associated with the TAU G389R mutation.

    PubMed

    Gemignani, A; Pietrini, P; Murrell, J R; Glazier, B S; Zolo, P; Guazzelli, M; Ghetti, B

    2005-02-01

    Sleep disturbances are found in the course of most dementing syndromes. We report a longitudinal polysomnographic and 18FDG-PET study in a 38-year-old male with FTDP17 carrying the Tau gene mutation G389R. All-night sleep EEG and wake cerebral glucose metabolism at rest (eyes/ears covered) of the preceding day were studied twice, eight months (Night 1; PET 1) and sixteen months (Night 2; PET 2) after the initial neurological evaluation. The Night 1 study showed sleep fragmentation associated to a short REM latency and a severe reduction of slow wave sleep, with relatively preserved NREM-REM sleep cycles; daytime PET 1 revealed severe cerebral glucose metabolic reductions in frontal and temporal areas, with relative preservation of remaining cortical regions and subcortical structures. On Night 2, the total sleep time was less than 5 hours, delta sleep and REM latency remained shortened and only two sleep cycles could be identified; daytime PET 2 exam revealed a greater cortical metabolic impairment and an involvement of subcortical brain regions as compared to PET 1. Post-mortem neuropathological data showed severe neuronal loss, spongiosis and gliosis that were mostly marked in cortical layers I, II, V and VI. In vivo, neurometabolic and post-mortem neuropathological data are consistent with and indicative of a severe dysfunction of intra- and trans-hemispheric regional connectivity and of cortico-thalamic circuits. These findings suggest that the decreased cortical and subcortical connectivity may have been the main pathophysiological mechanism responsible for delta sleep reduction and the cognitive decline.

  9. Sleep and Aging

    MedlinePlus

    ... There are two types of sleep: non-rapid eye movement -- or NREM sleep -- and rapid eye movement -- or REM sleep. NREM sleep includes four stages, ranging from light to deep sleep. Then we go into REM sleep, the most active ... During REM sleep, the eyes move back and forth beneath the eyelids and ...

  10. Relevance of the metabotropic glutamate receptor (mGluR5) in the regulation of NREM-REM sleep cycle and homeostasis: evidence from mGluR5 (-/-) mice.

    PubMed

    Ahnaou, A; Raeymaekers, L; Steckler, T; Drinkenbrug, W H I M

    2015-04-01

    Sleep is a homeostatically regulated behavior and sleep loss evokes a proportional increase in sleep time and delta slow wave activity. Glutamate and pharmacological modulation of the metabotropic glutamate receptors (mGluR) signaling have been implicated in the organization of vigilance states. Here, the role of the mGluR5 on homeostatic regulation of sleep-wake cycle and electroencephalographic (EEG) activity was examined in mGluR5 (-/-) mice. We first characterized the sleep-wake EEG phenotype in mGluR5 (-/-) and wild-type (WT) littermates mice by continuous recording for 72h of EEG, body temperature (BT) and locomotor activity (LMA). Next, we investigated the influence of sleep deprivation on the recovery sleep and EEG slow wave activity (1-4Hz) during NREM sleep to assess whether mGluR5 deletion affects the sleep homeostasis process. Like the control animals, mGluR5 (-/-) mice exhibited a clear-cut circadian sleep-wake architecture, however they showed reduced REM sleep time during the light phase with shorter REM sleep bouts and reduced state transitions in the NREM sleep-REM sleep cycle during the first and last 24h of the spontaneous 72h recording period. In addition, mGluR5 (-/-) mice had decreased slow EEG delta power during NREM sleep and enhanced LMA associated with elevated BT during the dark phase. Moreover, mGluR5 (-/-) mice exhibited reduced slow wave activity and sleep drive after sleep deprivation, indicating altered sleep homeostatic processes. The findings strongly indicate that mGluR5 is involved in shaping the stability of NREM sleep-REM sleep state transitions, NREM slow wave activity and homeostatic response to sleep loss.

  11. Parasomnias and movement disorders of sleep.

    PubMed

    Avidan, Alon Y

    2009-09-01

    Neurologists are often enlisted to help diagnose, evaluate, and manage a spectrum of abnormal spells during the night ranging from parasomnias to motor disturbance that span the sleep-wake cycle. Parasomnias are undesirable emotional or physical events that accompany sleep. These events typically occur during entry into sleep from wakefulness, or during arousals from sleep, and are often augmented by the sleep state. Some parasomnias, such as the rapid eye movement (REM) sleep behavior disorder may be extremely undesirable, while others such as somniloquy are often of little concern. The parasomnias include a spectrum of abnormal emotions, movements, behaviors, sensory perceptions, dream mentation, and autonomic activity. Basic physiologic drives, such as sex, hunger, and aggression, may manifest as sleep-related eating, sleep-related sexual behaviors, and sleep-related violence. Parasomnias have a very bizarre nature, but are readily explainable, diagnosable, and treatable. They are hypothesized to be due to changes in brain organization across multiple states of being, and are particularly apt to occur during the incomplete transition or oscillation from one sleep state to another. Parasomnias are often explained on the basis that wakefulness and sleep are not mutually exclusive states, and abnormal intrusion of wakefulness into non-REM (NREM) sleep produces arousal disorders, and intrusion of wakefulness into REM sleep produces REM sleep parasomnias and REM sleep behavior disorder (RBD). Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD), two closely related conditions that often result in disturbed sleep onset and sleep maintenance, are also reviewed in this article. Although the mechanisms that underlie idiopathic RLS or PLMD are not fully understood, there is currently substantial evidence that dopaminergic dysfunction is likely involved in both conditions. The discussion will conclude with the "other parasomnias" and sleep

  12. 2-AG into the lateral hypothalamus increases REM sleep and cFos expression in melanin concentrating hormone neurons in rats.

    PubMed

    Pérez-Morales, Marcel; De La Herrán-Arita, Alberto K; Méndez-Díaz, Mónica; Ruiz-Contreras, Alejandra E; Drucker-Colín, René; Prospéro-García, Oscar

    2013-07-01

    Orexins/hypocretins (OX) and melanin-concentrating hormone (MCH) neurons located in the lateral hypothalamus seem to modulate different stages of the sleep-wake cycle. OX are necessary for wakefulness and MCH appears to regulate rapid eye movement sleep (REMS). Likewise, endocannabinoids, the endogenous ligands for cannabinoid receptors 1 and 2 (CB1R, CB2R), also modulate REMS in rats. Moreover, it has been shown that the activation of the CB1R in the lateral hypothalamus of rats excites MCH neurons while inhibiting OX neurons in in vitro preparations. Hence, we assessed the effects of 2-arachidonoylglicerol (2-AG, an endocannabinoid) in the lateral hypothalamus on the sleep-wake cycle of rats. We also utilized the CB1R inverse agonist AM251 to further support the involvement of this receptor, and we performed double immunofluorescence experiments to detect c-Fos, as a marker of neural activation, in OX and in MCH neurons to determine which neurons were activated. Our results indicate that 2-AG increases REMS through CB1R activation, and increases c-Fos expression in MCH neurons. These results suggest that endocannabinoid activation of the CB1R in the lateral hypothalamus, which activates MCH neurons, is one mechanism by which REMS is triggered.

  13. The anorexigenic peptide cocaine-and-amphetamine-regulated transcript modulates rem-sleep in rats.

    PubMed

    Méndez-Díaz, M; Domínguez Martín, E; Pérez Morales, M; Ruiz-Contreras, A E; Navarro, L; Prospéro-García, O

    2009-12-01

    It is known that the sleep-waking cycle is modulated by several molecules that may also regulate food intake, among them several neuropeptides. The cocaine-and-amphetamine-regulated transcript has been studied in relation to food ingestion, but it seems to have several other functions that may include sleep regulation. In this context, we studied the effect of the intracerebroventricular administration of the cocaine-and-amphetamine-regulated transcript (0.15, 0.3, 0.6, 0.9nmol) on the sleep-waking cycle (12-h recordings), as well as its effect on food intake in rats. Additionally, we analyzed the neuronal activity as measured by c-Fos expression induced by the cocaine-and-amphetamine-regulated transcript in neurons of nuclei involved in the regulation of sleep and feeding behavior. Our main finding is that 0.3nmol of the cocaine-and-amphetamine-regulated transcript increases rapid-eye-movement sleep. In addition, our results further support that this neuropeptide triggers satiety; c-Fos expression suggested that the cocaine-and-amphetamine-regulated transcript activates specific hypothalamic nuclei without affecting other brain structures known to be involved in sleep regulation. These data further support the notion that a few neuropeptides are involved in the regulation of both the sleep-waking and the hunger-satiety cycles.

  14. Sleep-related epileptic behaviors and non-REM-related parasomnias: Insights from stereo-EEG.

    PubMed

    Gibbs, Steve A; Proserpio, Paola; Terzaghi, Michele; Pigorini, Andrea; Sarasso, Simone; Lo Russo, Giorgio; Tassi, Laura; Nobili, Lino

    2016-02-01

    During the last decade, many clinical and pathophysiological aspects of sleep-related epileptic and non-epileptic paroxysmal behaviors have been clarified. Advances have been achieved in part through the use of intracerebral recording methods such as stereo-electroencephalography (S-EEG), which has allowed a unique "in vivo" neurophysiological insight into focal epilepsy. Using S-EEG, the local features of physiological and pathological EEG activity in different cortical and subcortical structures have been better defined during the entire sleep-wake spectrum. For example, S-EEG has contributed to clarify the semiology of sleep-related seizures as well as highlight the specific epileptogenic networks involved during ictal activity. Moreover, intracerebral EEG recordings derived from patients with epilepsy have been valuable to study sleep physiology and specific sleep disorders. The occasional co-occurrence of NREM-related parasomnias in epileptic patients undergoing S-EEG investigation has permitted the recordings of such events, highlighting the presence of local electrophysiological dissociated states and clarifying the underlying pathophysiological substrate of such NREM sleep disorders. Based on these recent advances, the authors review and summarize the current and relevant S-EEG literature on sleep-related hypermotor epilepsies and NREM-related parasomnias. Finally, novel data and future research hypothesis will be discussed.

  15. Brain Basics: Understanding Sleep

    MedlinePlus

    ... Many of the body's cells also show increased production and reduced breakdown of proteins during deep sleep. ... deep sleep, REM sleep is associated with increased production of proteins. One study found that REM sleep ...

  16. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation

    PubMed Central

    Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Soto-Rodríguez, Sofía; González-Perez, Oscar

    2016-01-01

    Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P < 0.021). The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD. PMID:27579149

  17. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation.

    PubMed

    López-Armas, Gabriela; Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Jave-Suarez, Luis Felipe; Soto-Rodríguez, Sofía; Rusanova, Iryna; Acuña-Castroviejo, Dario; González-Perez, Oscar; González-Castañeda, Rocío Elizabeth

    2016-01-01

    Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P < 0.021). The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD.

  18. Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation.

    PubMed

    López-Armas, Gabriela; Flores-Soto, Mario Eduardo; Chaparro-Huerta, Verónica; Jave-Suarez, Luis Felipe; Soto-Rodríguez, Sofía; Rusanova, Iryna; Acuña-Castroviejo, Dario; González-Perez, Oscar; González-Castañeda, Rocío Elizabeth

    2016-01-01

    Purpose. The aim of this study was to assess the effect of melatonin in the proliferation of neural progenitors, melatonin concentration, and antiapoptotic proteins in the hippocampus of adult mice exposed to 96 h REM sleep deprivation (REMSD) prophylactic administration of melatonin for 14 days. Material and Methods. Five groups of Balb/C mice were used: (1) control, (2) REMSD, (3) melatonin (10 mg/kg) plus REMSD, (4) melatonin and intraperitoneal luzindole (once a day at 5 mg/kg) plus REMSD, and (5) luzindole plus REMSD. To measure melatonin content in hippocampal tissue we used HPLC. Bcl-2 and Bcl-xL proteins were measured by Western Blot and neurogenesis was determined by injecting 5-bromo-2-deoxyuridine (BrdU) and BrdU/nestin expressing cells in the subgranular zone of the dentate gyrus were quantified by epifluorescence. Results. The melatonin-treated REMSD group showed an increased neural precursor in 44% with respect to the REMSD group and in 28% when contrasted with the control group (P < 0.021). The melatonin-treated REMSD group also showed the highest expression of Bcl-2 and Bcl-xL as compared to the rest of the groups. Conclusion. The exogenous administration of melatonin restores the tissue levels of sleep-deprived group and appears to be an efficient neuroprotective agent against the deleterious effects of REMSD. PMID:27579149

  19. The role of dorsal raphe nucleus serotonergic and non-serotonergic neurons, and of their receptors, in regulating waking and rapid eye movement (REM) sleep.

    PubMed

    Monti, Jaime M

    2010-10-01

    Based on electrophysiological, neurochemical, genetic and neuropharmacological approaches it is currently accepted that serotonin (5-HT) functions to promote waking (W) and to inhibit rapid-eye movement sleep (REMS). The serotonin-containing neurons of the dorsal raphe nucleus (DRN) provide part of the serotonergic innervation of the telencephalon, diencephalon, mesencephalon and rhombencephalon of laboratory animals and man. The DRN has been subdivided into several clusters on the basis of differences in cellular morphology, expression of other neurotransmitters and afferent and efferent connections. These differences among subpopulations of 5-HT neurons may have important implications for neural mechanisms underlying 5-HT modulation of sleep and waking. The DRN contains 5-HT and non-5-HT neurons. The latter express a variety of substances including dopamine, γ-aminobutyric acid (GABA) and glutamate. In addition, nitric oxide and a number of neuropeptides have been characterized in the DRN. Available evidence tends to indicate that non-5-HT cells contribute to the regulation of the activity of 5-HT neurons during the sleep-wake cycle through local circuits and/or their mediation of the effects of afferent inputs. Mutant mice that do not express 5-HT(1A) or 5-HT(1B) receptor exhibit greater amounts of REMS than their wild-type couterparts. 5-HT(2A) and 5-HT(2C) receptor knockout mice show a significant increase of W and a reduction of slow wave sleep that is related, at least in part, to the increased release of norepinephrine and dopamine. A normal circadian sleep pattern is observed in 5-HT(7) receptor knockout mice; however, the mutants spend less time in REMS. Local microinjection of 5-HT(1B), 5-HT(2A/2C), 5-HT(3) and 5-HT(7) receptor agonists into the DRN selectively suppresses REMS in the rat. In contrast, microinjection of 5-HT(1A) receptor agonists promotes REMS. Similarly, local administration of the melanin-concentrating hormone or the GABA(A) receptor

  20. Spherical Harmonics Reveal Standing EEG Waves and Long-Range Neural Synchronization during Non-REM Sleep.

    PubMed

    Sivakumar, Siddharth S; Namath, Amalia G; Galán, Roberto F

    2016-01-01

    Previous work from our lab has demonstrated how the connectivity of brain circuits constrains the repertoire of activity patterns that those circuits can display. Specifically, we have shown that the principal components of spontaneous neural activity are uniquely determined by the underlying circuit connections, and that although the principal components do not uniquely resolve the circuit structure, they do reveal important features about it. Expanding upon this framework on a larger scale of neural dynamics, we have analyzed EEG data recorded with the standard 10-20 electrode system from 41 neurologically normal children and adolescents during stage 2, non-REM sleep. We show that the principal components of EEG spindles, or sigma waves (10-16 Hz), reveal non-propagating, standing waves in the form of spherical harmonics. We mathematically demonstrate that standing EEG waves exist when the spatial covariance and the Laplacian operator on the head's surface commute. This in turn implies that the covariance between two EEG channels decreases as the inverse of their relative distance; a relationship that we corroborate with empirical data. Using volume conduction theory, we then demonstrate that superficial current sources are more synchronized at larger distances, and determine the characteristic length of large-scale neural synchronization as 1.31 times the head radius, on average. Moreover, consistent with the hypothesis that EEG spindles are driven by thalamo-cortical rather than cortico-cortical loops, we also show that 8 additional patients with hypoplasia or complete agenesis of the corpus callosum, i.e., with deficient or no connectivity between cortical hemispheres, similarly exhibit standing EEG waves in the form of spherical harmonics. We conclude that spherical harmonics are a hallmark of spontaneous, large-scale synchronization of neural activity in the brain, which are associated with unconscious, light sleep. The analogy with spherical harmonics in

  1. Spherical Harmonics Reveal Standing EEG Waves and Long-Range Neural Synchronization during Non-REM Sleep

    PubMed Central

    Sivakumar, Siddharth S.; Namath, Amalia G.; Galán, Roberto F.

    2016-01-01

    Previous work from our lab has demonstrated how the connectivity of brain circuits constrains the repertoire of activity patterns that those circuits can display. Specifically, we have shown that the principal components of spontaneous neural activity are uniquely determined by the underlying circuit connections, and that although the principal components do not uniquely resolve the circuit structure, they do reveal important features about it. Expanding upon this framework on a larger scale of neural dynamics, we have analyzed EEG data recorded with the standard 10–20 electrode system from 41 neurologically normal children and adolescents during stage 2, non-REM sleep. We show that the principal components of EEG spindles, or sigma waves (10–16 Hz), reveal non-propagating, standing waves in the form of spherical harmonics. We mathematically demonstrate that standing EEG waves exist when the spatial covariance and the Laplacian operator on the head's surface commute. This in turn implies that the covariance between two EEG channels decreases as the inverse of their relative distance; a relationship that we corroborate with empirical data. Using volume conduction theory, we then demonstrate that superficial current sources are more synchronized at larger distances, and determine the characteristic length of large-scale neural synchronization as 1.31 times the head radius, on average. Moreover, consistent with the hypothesis that EEG spindles are driven by thalamo-cortical rather than cortico-cortical loops, we also show that 8 additional patients with hypoplasia or complete agenesis of the corpus callosum, i.e., with deficient or no connectivity between cortical hemispheres, similarly exhibit standing EEG waves in the form of spherical harmonics. We conclude that spherical harmonics are a hallmark of spontaneous, large-scale synchronization of neural activity in the brain, which are associated with unconscious, light sleep. The analogy with spherical harmonics

  2. Spherical Harmonics Reveal Standing EEG Waves and Long-Range Neural Synchronization during Non-REM Sleep.

    PubMed

    Sivakumar, Siddharth S; Namath, Amalia G; Galán, Roberto F

    2016-01-01

    Previous work from our lab has demonstrated how the connectivity of brain circuits constrains the repertoire of activity patterns that those circuits can display. Specifically, we have shown that the principal components of spontaneous neural activity are uniquely determined by the underlying circuit connections, and that although the principal components do not uniquely resolve the circuit structure, they do reveal important features about it. Expanding upon this framework on a larger scale of neural dynamics, we have analyzed EEG data recorded with the standard 10-20 electrode system from 41 neurologically normal children and adolescents during stage 2, non-REM sleep. We show that the principal components of EEG spindles, or sigma waves (10-16 Hz), reveal non-propagating, standing waves in the form of spherical harmonics. We mathematically demonstrate that standing EEG waves exist when the spatial covariance and the Laplacian operator on the head's surface commute. This in turn implies that the covariance between two EEG channels decreases as the inverse of their relative distance; a relationship that we corroborate with empirical data. Using volume conduction theory, we then demonstrate that superficial current sources are more synchronized at larger distances, and determine the characteristic length of large-scale neural synchronization as 1.31 times the head radius, on average. Moreover, consistent with the hypothesis that EEG spindles are driven by thalamo-cortical rather than cortico-cortical loops, we also show that 8 additional patients with hypoplasia or complete agenesis of the corpus callosum, i.e., with deficient or no connectivity between cortical hemispheres, similarly exhibit standing EEG waves in the form of spherical harmonics. We conclude that spherical harmonics are a hallmark of spontaneous, large-scale synchronization of neural activity in the brain, which are associated with unconscious, light sleep. The analogy with spherical harmonics in

  3. Rhythmic dendritic Ca2+ oscillations in thalamocortical neurons during slow non-REM sleep-related activity in vitro.

    PubMed

    Errington, Adam C; Hughes, Stuart W; Crunelli, Vincenzo

    2012-08-15

    The distribution of T-type Ca2+ channels along the entire somatodendritic axis of sensory thalamocortical (TC) neurons permits regenerative propagation of low threshold spikes (LTS) accompanied by global dendritic Ca2+ influx. Furthermore, T-type Ca2+ channels play an integral role in low frequency oscillatory activity (<1–4 Hz) that is a defining feature of TC neurons. Nonetheless, the dynamics of T-type Ca2+ channel-dependent dendritic Ca2+ signalling during slow sleep-associated oscillations remains unknown. Here we demonstrate using patch clamp recording and two-photon Ca2+ imaging of dendrites from cat TC neurons undergoing spontaneous slow oscillatory activity that somatically recorded δ (1–4 Hz) and slow (<1 Hz) oscillations are associated with rhythmic and sustained global oscillations in dendritic Ca2+. In addition, our data reveal the presence of LTS-dependent Ca2+ transients (Δ[Ca2+]) in dendritic spine-like structures on proximal TC neuron dendrites during slow (<1 Hz) oscillations whose amplitudes are similar to those observed in the dendritic shaft. We find that the amplitude of oscillation associated Δ[Ca2+] do not vary significantly with distance from the soma whereas the decay time constant (τdecay) of Δ[Ca2+] decreases significantly in more distal dendrites. Furthermore, τdecay of dendritic Δ[Ca2+] increases significantly as oscillation frequency decreases from δ to slow frequencies where pronounced depolarised UP states are observed. Such rhythmic dendritic Ca2+ entry in TC neurons during sleep-related firing patterns could be an important factor in maintaining the oscillatory activity and associated biochemical signalling processes, such as synaptic downscaling, that occur in non-REM sleep.

  4. REM sleep-like episodes of motoneuronal depression and respiratory rate increase are triggered by pontine carbachol microinjections in in situ perfused rat brainstem preparation.

    PubMed

    Brandes, Ivo F; Stettner, Georg M; Mörschel, Michael; Kubin, Leszek; Dutschmann, Mathias

    2011-05-01

    Hypoglossal nerve activity (HNA) controls the position and movements of the tongue. In persons with compromised upper airway anatomy, sleep-related hypotonia of the tongue and other pharyngeal muscles causes increased upper airway resistance, or total upper airway obstructions, thus disrupting both sleep and breathing. Hypoglossal nerve activity reaches its nadir, and obstructive episodes are longest and most severe, during rapid eye movement stage of sleep (REMS). Microinjections of a cholinergic agonist, carbachol, into the pons have been used in vivo to investigate the mechanisms of respiratory control during REMS. Here, we recorded inspiratory-modulated phrenic nerve activity and HNA and microinjected carbachol (25-50 nl, 10 mm) into the pons in an in situ perfused working heart-brainstem rat preparation (WHBP), an ex vivo model previously validated for studies of the chemical and reflex control of breathing. Carbachol microinjections were made into 40 sites in 33 juvenile rat preparations and, at 24 sites, they triggered depression of HNA with increased respiratory rate and little change of phrenic nerve activity, a pattern akin to that during natural REMS in vivo. The REMS-like episodes started 151 ± 73 s (SD) following microinjections, lasted 20.3 ± 4.5 min, were elicited most effectively from the dorsal part of the rostral nucleus pontis oralis, and were prevented by perfusion of the preparation with atropine. The WHBP offers a novel model with which to investigate cellular and neurochemical mechanisms of REMS-related upper airway hypotonia in situ without anaesthesia and with full control over the cellular environment.

  5. Gudden's dorsal tegmental nucleus is activated in carbachol-induced active (REM) sleep and active wakefulness.

    PubMed

    Torterolo, Pablo; Sampogna, Sharon; Morales, Francisco R; Chase, Michael H

    2002-07-19

    Previous studies have shown that GABAergic processes in the ponto-mesencephalic region of the brainstem are involved in the generation of wakefulness and active sleep (AS). The dorsal and ventral tegmental nuclei of Gudden (DTN and VTN, respectively) are known to contain a large population of GABAergic neurons. In the present study, utilizing Fos immunoreactivity as a marker of neuronal activity, it was determined that GABAergic DTN pars dorsalis neurons are active during active wakefulness and AS induced by carbachol, but not during quiet wakefulness or quiet sleep. In contrast, no differences in the number of Fos immunoreactive neurons were observed in the DTN pars ventralis and VTN across behavioral states.

  6. The pontine REM switch: past and present.

    PubMed

    Fuller, Patrick M; Saper, Clifford B; Lu, Jun

    2007-11-01

    Rapid eye movement (REM) sleep is a behavioural state characterized by activation of the cortical and hippocampal EEG, rapid eye movements and muscle atonia. For the past 30 years, the most widely accepted neural circuitry model for the regulation of REM sleep has emphasized reciprocal inhibitory interactions between pontine brainstem monoaminergic and cholinergic neurons. In general support of the reciprocal interaction model, neuropharmacological studies have shown that cholinergic agonists promote REM sleep and muscarinic antagonists and monoamines inhibit REM sleep. It has nevertheless proven difficult to reconcile both the theoretical framework of this model and the pharmacological data with the fact that selective lesions of either cholinergic or monoaminergic (noradrenergic, serotoninergic or dopaminergic) nuclei in the brainstem have relatively limited effects on REM sleep. Recent work by our laboratory has revealed the presence of non-cholinergic and non-monoaminergic mutually inhibitory REM-off and REM-on areas in the mesopontine tegmentum that may form the neuroanatomical basis of the switching circuitry for REM sleep. These findings posit a REM switching circuitry model that is analogous to an electronic 'flip-flop' switch. In this flip-flop switch arrangement, GABAergic REM-on neurons (located in the sublaterodorsal tegmental nucleus (SLD)) inhibit GABAergic REM-off neurons (located in the ventrolateral periaqueductal grey matter (vlPAG) and lateral pontine tegmentum (LPT)) and vice versa. In the REM-on area are two populations of glutamatergic neurons, the first of which projects to the basal forebrain and regulates EEG components of REM sleep and the second of which projects to the ventromedial medulla and spinal cord and regulates atonia during REM sleep. Our findings demonstrating independent pathways mediating atonia and the EEG components of REM provide a basis for their occasional dissociation in pathological states, e.g. REM sleep behaviour

  7. A novel NREM and REM parasomnia with sleep breathing disorder associated with antibodies against IgLON5: a case series, pathological features, and characterization of the antigen

    PubMed Central

    Sabater, Lidia; Gaig, Carles; Gelpi, Ellen; Bataller, Luis; Lewerenz, Jan; Torres-Vega, Estefanía; Contreras, Angeles; Giometto, Bruno; Compta, Yaroslau; Embid, Cristina; Vilaseca, Isabel; Iranzo, Alex; Santamaría, Joan; Dalmau, Josep; Graus, Francesc

    2014-01-01

    Summary Background Autoimmunity may be involved in sleep and neurodegenerative disorders. We aimed to describe a neurological syndrome with prominent sleep dysfunction and antibodies to a previously unknown neuronal antigen. Methods In this observational study, clinical and video-polysomnography (V- PSG) investigations identified a novel sleep disorder in three patients referred to the Sleep Unit of Hospital Clinic University of Barcelona for abnormal sleep behaviors and obstructive sleep apnea(OSA). They had antibodies against a neuronal surface antigen also present in five additional patients referred to our laboratory for antibody studies. These five patients had been evaluated with PSG and in two, the study was done or reviewed in our Sleep Unit. Two patients underwent postmortem brain examination. Immunoprecipitation and mass spectrometry were used to characterize the antigen and to develop a diagnostic test. Serum or CSF from 285 patients with neurodegenerative, sleep, or autoimmune disorders served as controls. Findings All eight patients (five women; range: 52–76 years, median 59) had abnormal sleep movements and behaviors and OSA confirmed by PSG. Six patients had a chronic evolution (range 2–12 years, median 5.5); in four the sleep disorder was the initial and most prominent feature, and in two it was preceded by gait instability, and followed by dysarthria, dysphagia, ataxia, or chorea. Two patients had a rapid evolution with disequilibrium, dysarthria, dysphagia, and central hypoventilation, and died two and six months after symptom onset. In 5/5 patients, the V-PSG reviewed in our Unit disclosed OSA, stridor, and abnormal sleep architecture with undifferentiated NREM sleep or poorly structured stage N2 with simple movements and finalistic behaviors, normalization of NREM sleep by the end of the night, and REM sleep behavior disorder. Four/4 patients carried the HLA-DRB1*1001 and HLA-DQB1*0501 alleles. All patients had antibodies (mainly IgG4

  8. EEG spectral power in phasic and tonic REM sleep: different patterns in young adults and children.

    PubMed

    Simor, Péter; Gombos, Ferenc; Szakadát, Sára; Sándor, Piroska; Bódizs, Róbert

    2016-06-01

    Rapid eye movement sleep is composed of phasic and tonic periods, two distinguishable microstates in terms of arousal thresholds and sensory processing. Background electroencephalogram oscillations are also different between periods with (phasic state) and periods without (tonic state) eye movements. In Study 1, previous findings analysing electroencephalogram spectral power in phasic and tonic rapid eye movement sleep were replicated, and analyses extended to the high gamma range (52-90 Hz). In Study 2, phasic and tonic spectral power differences within a group of 4-8-year-old children were examined. Based on the polysomnographic data of 20 young adults, the phasic state yielded increased delta and theta power in anterior sites, as well as generally decreased high alpha and beta power in comparison to the tonic state. Moreover, phasic periods exhibited greater spectral power in the lower and the higher gamma band. Interestingly, children (n = 18) exhibited a different pattern, showing increased activity in the low alpha range during phasic periods. Moreover, during phasic in contrast to tonic rapid eye movement sleep, increased low and high gamma and enhanced low gamma band power emerged in anterior and posterior regions, respectively. The current findings show that spectral activity within the high gamma range substantially contributes to the differences between phasic and tonic rapid eye movement sleep, especially in adults. Moreover, the current data underscore the heterogeneity of rapid eye movement sleep, and point to marked differences between young adults and children regarding phasic/tonic electroencephalogram spectral power. These results suggest that the differentiation between phasic and tonic rapid eye movement periods undergoes maturation. PMID:26762188

  9. EEG spectral power in phasic and tonic REM sleep: different patterns in young adults and children.

    PubMed

    Simor, Péter; Gombos, Ferenc; Szakadát, Sára; Sándor, Piroska; Bódizs, Róbert

    2016-06-01

    Rapid eye movement sleep is composed of phasic and tonic periods, two distinguishable microstates in terms of arousal thresholds and sensory processing. Background electroencephalogram oscillations are also different between periods with (phasic state) and periods without (tonic state) eye movements. In Study 1, previous findings analysing electroencephalogram spectral power in phasic and tonic rapid eye movement sleep were replicated, and analyses extended to the high gamma range (52-90 Hz). In Study 2, phasic and tonic spectral power differences within a group of 4-8-year-old children were examined. Based on the polysomnographic data of 20 young adults, the phasic state yielded increased delta and theta power in anterior sites, as well as generally decreased high alpha and beta power in comparison to the tonic state. Moreover, phasic periods exhibited greater spectral power in the lower and the higher gamma band. Interestingly, children (n = 18) exhibited a different pattern, showing increased activity in the low alpha range during phasic periods. Moreover, during phasic in contrast to tonic rapid eye movement sleep, increased low and high gamma and enhanced low gamma band power emerged in anterior and posterior regions, respectively. The current findings show that spectral activity within the high gamma range substantially contributes to the differences between phasic and tonic rapid eye movement sleep, especially in adults. Moreover, the current data underscore the heterogeneity of rapid eye movement sleep, and point to marked differences between young adults and children regarding phasic/tonic electroencephalogram spectral power. These results suggest that the differentiation between phasic and tonic rapid eye movement periods undergoes maturation.

  10. Inhibitory and excitatory amino acid neurotransmitters are utilized by the projection from the dorsal deep mesencephalic nucleus to the sublaterodorsal nucleus REM sleep induction zone.

    PubMed

    Liang, Chang-Lin; Quang Nguyen, Tin; Marks, Gerald A

    2014-06-01

    The sublaterodorsal nucleus (SLD) in the pons of the rat is a locus supporting short-latency induction of a REM sleep-like state following local application of a GABAA receptor antagonist or kainate, glutamate receptor agonist. One putatively relevant source of these neurotransmitters is from the region of the deep mesencephalic nucleus (DpMe) just ventrolateral to the periaquiductal gray, termed the dorsal DpMe (dDpMe). Here, the amino acid neurotransmitter innervation of SLD from dDpMe was studied utilizing anterograde tract-tracing with biotinylated dextranamine (BDA) and fluorescence immunohistochemistry visualized with laser scanning confocal microscopy. Both markers for inhibitory and excitatory amino acid neurotransmitters were found in varicose axon fibers in SLD originating from dDpMe. Vesicular glutamate transporter2 (VGLUT2) represented the largest number of anterogradely labeled varicosities followed by vesicular GABA transporter (VGAT). Numerous VGAT and VGLUT2 labeled varicosities were observed apposed to dDpMe-labeled axon fibers indicating both excitatory and inhibitory presynaptic, local modulation within the SLD. Some double-labeled BDA/VGAT varicosities were seen apposed to small somata labeled for glutamate consistent with being presynaptic to the phenotype of REM sleep-active SLD neurons. Results found support the current theoretical framework of the interaction of dDpMe and SLD in control of REM sleep, while also indicating operation of mechanisms with a greater level of complexity.

  11. Short Meditation Trainings Enhance Non-REM Sleep Low-Frequency Oscillations

    PubMed Central

    Dentico, Daniela; Ferrarelli, Fabio; Riedner, Brady A.; Smith, Richard; Zennig, Corinna; Lutz, Antoine; Tononi, Giulio; Davidson, Richard J.

    2016-01-01

    Study Objectives We have recently shown higher parietal-occipital EEG gamma activity during sleep in long-term meditators compared to meditation-naive individuals. This gamma increase was specific for NREM sleep, was present throughout the entire night and correlated with meditation expertise, thus suggesting underlying long-lasting neuroplastic changes induced through prolonged training. The aim of this study was to explore the neuroplastic changes acutely induced by 2 intensive days of different meditation practices in the same group of practitioners. We also repeated baseline recordings in a meditation-naive cohort to account for time effects on sleep EEG activity. Design High-density EEG recordings of human brain activity were acquired over the course of whole sleep nights following intervention. Setting Sound-attenuated sleep research room. Patients or Participants Twenty-four long-term meditators and twenty-four meditation-naïve controls. Interventions Two 8-h sessions of either a mindfulness-based meditation or a form of meditation designed to cultivate compassion and loving kindness, hereafter referred to as compassion meditation. Measurements and Results We found an increase in EEG low-frequency oscillatory activities (1–12 Hz, centered around 7–8 Hz) over prefrontal and left parietal electrodes across whole night NREM cycles. This power increase peaked early in the night and extended during the third cycle to high-frequencies up to the gamma range (25–40 Hz). There was no difference in sleep EEG activity between meditation styles in long-term meditators nor in the meditation naïve group across different time points. Furthermore, the prefrontal-parietal changes were dependent on meditation life experience. Conclusions This low-frequency prefrontal-parietal activation likely reflects acute, meditation-related plastic changes occurring during wakefulness, and may underlie a top-down regulation from frontal and anterior parietal areas to the posterior

  12. MCHergic projections to the nucleus pontis oralis participate in the control of active (REM) sleep.

    PubMed

    Torterolo, Pablo; Sampogna, Sharon; Chase, Michael H

    2009-05-01

    Neurons that utilize melanin-concentrating hormone (MCH) as a neuromodulator are located in the lateral hypothalamus and incerto-hypothalamic area and project diffusely throughout the central nervous system, including areas that participate in the generation and maintenance of sleep and wakefulness. Recent studies have shown that hypothalamic MCHergic neurons are active during active sleep (AS), and that intraventricular microinjections of MCH induce AS sleep; however, there are no data available regarding the manner in which MCHergic neurons participate in the control of this behavioral state. Utilizing immunohistochemical and retrograde tracing techniques, we examined, in the cat, projections from MCHergic neurons to the nucleus pontis oralis (NPO), which is considered to be the executive area that is responsible for the generation and maintenance of AS. In addition, we explored the effects on sleep and waking states produced by the microinjection of MCH into the NPO. We first determined that MCHergic fibers and terminals are present in the NPO. We also found that when a retrograde tracer (cholera toxin subunit B) was placed in the NPO MCHergic neurons of the hypothalamus were labeled. When MCH was microinjected into the NPO, there was a significant increase in the amount of AS (19.8+/-1.4% versus 11.9+/-0.2%, P<0.05) and a significant decrease in the latency to AS (10.4+/-4.2 versus 26.6+/-2.3 min, P<0.05). The preceding anatomical and functional data support our hypothesis that the MCHergic system participates in the regulation of AS by modulating neuronal activity in the NPO. PMID:19269278

  13. MCHergic projections to the nucleus pontis oralis participate in the control of active (REM) sleep.

    PubMed

    Torterolo, Pablo; Sampogna, Sharon; Chase, Michael H

    2009-05-01

    Neurons that utilize melanin-concentrating hormone (MCH) as a neuromodulator are located in the lateral hypothalamus and incerto-hypothalamic area and project diffusely throughout the central nervous system, including areas that participate in the generation and maintenance of sleep and wakefulness. Recent studies have shown that hypothalamic MCHergic neurons are active during active sleep (AS), and that intraventricular microinjections of MCH induce AS sleep; however, there are no data available regarding the manner in which MCHergic neurons participate in the control of this behavioral state. Utilizing immunohistochemical and retrograde tracing techniques, we examined, in the cat, projections from MCHergic neurons to the nucleus pontis oralis (NPO), which is considered to be the executive area that is responsible for the generation and maintenance of AS. In addition, we explored the effects on sleep and waking states produced by the microinjection of MCH into the NPO. We first determined that MCHergic fibers and terminals are present in the NPO. We also found that when a retrograde tracer (cholera toxin subunit B) was placed in the NPO MCHergic neurons of the hypothalamus were labeled. When MCH was microinjected into the NPO, there was a significant increase in the amount of AS (19.8+/-1.4% versus 11.9+/-0.2%, P<0.05) and a significant decrease in the latency to AS (10.4+/-4.2 versus 26.6+/-2.3 min, P<0.05). The preceding anatomical and functional data support our hypothesis that the MCHergic system participates in the regulation of AS by modulating neuronal activity in the NPO.

  14. GABAergic mechanisms in the pedunculopontine tegmental nucleus of the cat promote active (REM) sleep.

    PubMed

    Torterolo, Pablo; Morales, Francisco R; Chase, Michael H

    2002-07-19

    The pedunculopontine tegmental nucleus (PPT) has been implicated in the generation and/or maintenance of both active sleep (AS) and wakefulness (W). GABAergic neurons are present within this nucleus and recent studies have shown that these neurons are active during AS. In order to examine the role of mesopontine GABAergic processes in the generation of AS, the GABA(A) agonist muscimol and the GABA(A) antagonist bicuculline were microinjected into the PPT of chronic cats that were prepared for recording the states of sleep and wakefulness. Muscimol increased the time spent in AS by increasing the frequency and duration of AS episodes; this increase in AS was at the expense of the time spent in wakefulness. A decrease in PGO density during AS was also observed following the microinjection of muscimol. On the other hand, bicuculline decreased both AS and quiet sleep and increased the time spent in wakefulness. These data suggest that GABA acts on GABA(A) receptors within the PPT to facilitate the generation of AS by suppressing the activity of waking-related processes within this nucleus. PMID:12106660

  15. Fear-conditioned suppression of REM sleep: relationship to Fos expression patterns in limbic and brainstem regions in BALB/cJ mice.

    PubMed

    Liu, Xianling; Tang, Xiangdong; Sanford, Larry D

    2003-11-21

    In fear conditioning, shock training (ST) and shock-associated fearful cues (FC) produce relatively selective decreases in rapid eye movement sleep (REM) in mice that vary with strain, and can last for an extended period. We examined sleep in BALB/cJ mice over 6 h after ST and FC, and in handling and tone control conditions. In separate groups of mice, we used immunohistochemical techniques to examine Fos expression in limbic and brainstem regions involved in fear conditioning and in the regulation of REM in 2-h intervals over this period. Significant reductions in REM were observed at 2 and 4 h after ST. Fos expression in the brainstem was significantly elevated at 2 h after ST in the laterodorsal and peduculopontine tegmentum, up to 4 h in the dorsal raphe nucleus (DRN) and up to 6 h in the locus coeruleus (LC). Significant elevations in Fos expression were observed in several regions of the amygdala up to 4 and 6 h after ST. Decreases in REM after FC were significant at 2 h. Increased Fos expression was observed in LC at 2 h and in DRN up to 6 h after FC. Increased Fos expression in the amygdala was observed in several regions of the amygdala at 2 h after FC, but not longer. Significant changes in Fos expression in the central nucleus of the amygdala were not observed at any time point examined or in any condition. The data are discussed with respect to the putative role of brainstem nuclei in regulating REM and the role of the amygdala in conditioned fear.

  16. Tail-pinch stress and REM sleep deprivation differentially affect sensorimotor gating function in modafinil-treated rats.

    PubMed

    Liu, Yia-Ping; Tung, Che-Se; Chuang, Chia-Hsin; Lo, Shih-Mao; Ku, Yu-Chi

    2011-05-16

    Prepulse inhibition (PPI) is a phenomenon in which a mild stimulus attenuates a cross-modality startle response to later intense stimulation. PPI is thought to index the central inhibitory mechanism through which behavioural responses are filtered. The present study compared the effects of two stress paradigms on the acoustic startle response (ASR) and on PPI in a rat model. The tail-pinch (TP) method produces an acute and immediate stressful condition, whereas rapid eye movement (REM) sleep deprivation (REMSD) leads to a more persistent and long-term stress. Our results demonstrated that in rats, TP stress reduced the size of the ASR, and REMSD impaired PPI. The wake-promoting agent modafinil (MOD) had no effect on PPI if given alone. However, MOD reduced the ASR and PPI under TP stress, whereas only PPI was reduced by MOD after 96 h of REMSD. These results suggest that distinct stress paradigms differentially mediated sensorimotor gating abilities in terms of either responsiveness to the stimulus or information-filtering capabilities.

  17. Depressed REM Sleep Behavior Disorder Patients Are Less Likely to Recall Enacted Dreams than Non-Depressed Ones

    PubMed Central

    Lee, Hyeong Gon; Choi, Jae Won; Lee, Yu Jin

    2016-01-01

    Objective REM sleep behavior disorder (RBD) is associated with psychiatric symptoms, such as anxiety and alexithymia. However, only a few studies on the relationship between depression and RBD have been published. In this study, we investigated the occurrence of depression and associated factors in patients with RBD. Methods In total 94 patients (mean age: 61.9±12.7 years, male: 70.2%) diagnosed as RBD were examined using detailed clinical histories, the Beck Depression Inventory (BDI), the Epworth Sleepiness Scale (ESS), and nocturnal polysomnography (PSG). Results The mean BDI score of all patients was 12.4±10.3 and 44.7% of RBD patients showed depressed mood (BDI >11 points). Depressed RBD patients were less able to recall enacted dreams than were non-depressed patients (61.9% vs. 86.5%, p=0.008). Logistic regression analysis showed that failure to recall enacted dreams was significantly associated with depression, after controlling for confounding variables including the respiratory disturbance index and a history of psychiatric disorders (odds ratio=0.323, p=0.041). Conclusion In this study, 44.7% of RBD patients were found to suffer from depressed mood. And, depression was found to be associated with reduced ability to recall enacted dreams. We suggest that routine evaluation of depression be performed in RBD patients, particularly when failure to recall enacted dreams is evident. We speculate that such failure may be associated with emotional dysregulation or neurodegeneration. PMID:27081385

  18. Idiopathic pulmonary fibrosis and sleep disorders: no longer strangers in the night.

    PubMed

    Schiza, Sophia; Mermigkis, Charalampos; Margaritopoulos, George A; Daniil, Zoi; Harari, Sergio; Poletti, Venerino; Renzoni, Elizabetta A; Torre, Olga; Visca, Dina; Bouloukaki, Isolde; Sourvinos, George; Antoniou, Katerina M

    2015-06-01

    The prevalence of obstructive sleep apnoea (OSA) is continuously increasing in patients with idiopathic pulmonary fibrosis (IPF) and, for the first time, the recent IPF guidelines recognise OSA as an important associated comorbidity that can affect patient's survival. Thus, it becomes conceivable that clinicians should refer patients with newly diagnosed IPF to sleep centres for the diagnosis and treatment of OSA as well as for addressing issues regarding the reduced compliance of patients with continuous positive airway pressure therapy. The discovery of biomarkers common to both disorders may help early diagnosis, institution of the most appropriate treatment and follow-up of patients. Better understanding of epigenetic changes may provide useful information about pathogenesis and, possibly, development of new drugs for a dismal disease like IPF.

  19. Idiopathic pulmonary fibrosis and sleep disorders: no longer strangers in the night.

    PubMed

    Schiza, Sophia; Mermigkis, Charalampos; Margaritopoulos, George A; Daniil, Zoi; Harari, Sergio; Poletti, Venerino; Renzoni, Elizabetta A; Torre, Olga; Visca, Dina; Bouloukaki, Isolde; Sourvinos, George; Antoniou, Katerina M

    2015-06-01

    The prevalence of obstructive sleep apnoea (OSA) is continuously increasing in patients with idiopathic pulmonary fibrosis (IPF) and, for the first time, the recent IPF guidelines recognise OSA as an important associated comorbidity that can affect patient's survival. Thus, it becomes conceivable that clinicians should refer patients with newly diagnosed IPF to sleep centres for the diagnosis and treatment of OSA as well as for addressing issues regarding the reduced compliance of patients with continuous positive airway pressure therapy. The discovery of biomarkers common to both disorders may help early diagnosis, institution of the most appropriate treatment and follow-up of patients. Better understanding of epigenetic changes may provide useful information about pathogenesis and, possibly, development of new drugs for a dismal disease like IPF. PMID:26028644

  20. Sleep, stress, neurocognitive profile and health-related quality of life in adolescents with idiopathic musculoskeletal pain

    PubMed Central

    Molina, Juliana; Dos Santos, Flávia Heloísa; Terreri, Maria Teresa R. A.; Fraga, Melissa Mariti; Silva, Simone Guerra; Hilário, Maria Odete E.; Len, Claudio A.

    2012-01-01

    OBJECTIVES: The aims of this study were to measure levels of sleep, stress, and depression, as well as health-related quality of life, and to assess the neurocognitive profiles in a sample of adolescents with idiopathic musculoskeletal pain. METHODS: Nineteen adolescents with idiopathic musculoskeletal pain and 20 age-matched healthy control subjects were evaluated regarding their levels of sleep and stress, as well as quality of life, and underwent neurocognitive testing. RESULTS: The sample groups consisted predominantly of females (84%), and the socioeconomic status did not differ between the two groups. In addition, the occurrence of depressive symptoms was similar between the two groups; specifically, 26% of the idiopathic musculoskeletal pain patients and 30% of the control subjects had scores indicative of depression. Teenagers in the group with idiopathic musculoskeletal pain reported poorer quality of life and sleep scores than those in the control group. Regarding stress, patients had worse scores than the control group; whereas 79% of the adolescents with idiopathic musculoskeletal pain met the criteria for a diagnosis of stress, only 35% of the adolescents in the control group met the criteria. In both groups, we observed scores that classified adolescents as being in the resistance phase (intermediate) and exhaustion phase (pathological) of distress. However, the idiopathic musculoskeletal pain group more frequently reported symptomatic complaints of physical and emotional distress. The neurocognitive assessment showed no significant impairments in either group. CONCLUSION: Adolescents with idiopathic musculoskeletal pain did not exhibit cognitive impairments. However, adolescents with idiopathic musculoskeletal pain did experience intermediate to advanced psychological distress and lower health-related quality of life, which may increase their risk of cognitive dysfunction in the future. PMID:23070339

  1. Microinjection of the 5-HT7 receptor antagonist SB-269970 into the rat brainstem and basal forebrain: site-dependent effects on REM sleep.

    PubMed

    Monti, Jaime M; Leopoldo, Marcello; Jantos, Héctor; Lagos, Patricia

    2012-08-01

    The effects of SB-269970, a selective 5-HT7 receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The 5-HT7 receptor ligand was microinjected into the horizontal limb of the diagonal band of Broca (HDB) and the laterodorsal tegmental nucleus (LDT) during the light period of the 12-h light/12-h dark cycle. For comparative purposes the compound was administered systemically and, in addition, injected directly into the dorsal raphe nucleus (DRN). Microinjection of SB-269970 into the HDB and the DRN induced a significant reduction of rapid-eye-movement sleep (REMS). Similar effects were observed after systemic administration of the 5-HT7 receptor antagonist. On the other hand, local infusion of the compound into the LDT provoked the opposite effect. It is proposed that the deactivation of GABAergic cells located in the HDB, DRN and LDT is responsible for the changes induced by SB-269970 on REM sleep values. It is suggested that the antidepressant effect of the 5-HT7 receptor antagonist could partly depend on the involvement of neuronal systems located in the DRN and the HDB.

  2. State- or trait-like individual differences in dream recall: preliminary findings from a within-subjects study of multiple nap REM sleep awakenings

    PubMed Central

    Scarpelli, Serena; Marzano, Cristina; D’Atri, Aurora; Gorgoni, Maurizio; Ferrara, Michele; De Gennaro, Luigi

    2015-01-01

    We examined the question whether the role of EEG oscillations in predicting presence/absence of dream recall (DR) is explained by “state-” or “trait-like” factors. Six healthy subjects were awakened from REM sleep in a within-subjects design with multiple naps, until a recall and a non-recall condition were obtained. Naps were scheduled in the early afternoon and were separated by 1 week. Topographical EEG data of the 5-min of REM sleep preceding each awakening were analyzed by power spectral analysis [Fast Fourier Transform (FFT)] and by a method to detect oscillatory activity [Better OSCillations (BOSC)]. Both analyses show that REC is associated to higher frontal theta activity (5–7 Hz) and theta oscillations (6.06 Hz) compared to NREC condition, but only the second comparison reached significance. Our pilot study provides support to the notion that sleep and wakefulness share similar EEG correlates of encoding in episodic memories, and supports the “state-like hypothesis”: DR may depend on the physiological state related to the sleep stage from which the subject is awakened rather than on a stable individual EEG pattern. PMID:26217264

  3. The Phenomenon of Sleep Paralysis

    MedlinePlus

    ... of sleep where vivid dreams occur (known as REM sleep), your arms and legs are temporarily paralyzed so ... alien abductions." Since breathing can be irregular during REM sleep, those experiencing sleep paralysis may feel like they' ...

  4. Persistent Hyperdopaminergia Decreases the Peak Frequency of Hippocampal Theta Oscillations during Quiet Waking and REM Sleep

    PubMed Central

    Dzirasa, Kafui; Santos, Lucas M.; Ribeiro, Sidarta; Stapleton, Jennifer; Gainetdinov, Raul R.; Caron, Marc G.; Nicolelis, Miguel A. L.

    2009-01-01

    Long-term changes in dopaminergic signaling are thought to underlie the pathophysiology of a number of psychiatric disorders. Several conditions are associated with cognitive deficits such as disturbances in attention processes and learning and memory, suggesting that persistent changes in dopaminergic signaling may alter neural mechanisms underlying these processes. Dopamine transporter knockout (DAT-KO) mice exhibit a persistent five-fold increase in extracellular dopamine levels. Here, we demonstrate that DAT-KO mice display lower hippocampal theta oscillation frequencies during baseline periods of waking and rapid-eye movement sleep. These altered theta oscillations are not reversed via treatment with the antidopaminergic agent haloperidol. Thus, we propose that persistent hyperdopaminergia, together with secondary alterations in other neuromodulatory systems, results in lower frequency activity in neural systems responsible for various cognitive processes. PMID:19381303

  5. Olfactory impairment in the rotenone model of Parkinson’s disease is associated with bulbar dopaminergic D2 activity after REM sleep deprivation

    PubMed Central

    Rodrigues, Lais S.; Targa, Adriano D. S.; Noseda, Ana Carolina D.; Aurich, Mariana F.; Da Cunha, Cláudio; Lima, Marcelo M. S.

    2014-01-01

    Olfactory and rapid eye movement (REM) sleep deficits are commonly found in untreated subjects with a recent diagnosis of Parkinson’s disease (PD). Additionally, different studies report declines in olfactory performance during a short period of sleep deprivation. Mechanisms underlying these clinical manifestations are poorly understood, and impairment of dopamine (DA) neurotransmission in the olfactory bulb and the nigrostriatal pathway may have important roles in olfaction and REM sleep disturbances. Therefore, we hypothesized that modulation of the dopaminergic D2 receptors in the olfactory bulb could provide a more comprehensive understanding of the olfactory deficits in PD and REM sleep deprivation (REMSD). We decided to investigate the olfactory, neurochemical, and histological alterations generated through the administration of piribedil (a selective D2 agonist) or raclopride (a selective D2 antagonist) within the glomerular layer of the olfactory bulb, in rats subjected to intranigral rotenone and REMSD. Our findings provide evidence of the occurrence of a negative correlation (r = −0.52, P = 0.04) between the number of periglomerular TH-ir neurons and the bulbar levels of DA in the rotenone, but not sham, groups. A significant positive correlation (r = 0.34, P = 0.03) was observed between nigrostriatal DA levels and olfactory discrimination index (DI) for the sham groups, indicating that increased DA levels in the substantia nigra pars compacta (SNpc) are associated with enhanced olfactory discrimination performance. Also, increased levels in bulbar and striatal DA were induced by piribedil in the rotenone control and rotenone REMSD groups, consistent with reductions in the DI. The present evidence reinforce the idea that DA produced by periglomerular neurons, particularly the bulbar dopaminergic D2 receptors, is an essential participant in olfactory discrimination processes, as the SNpc, and the striatum. PMID:25520618

  6. Olfactory impairment in the rotenone model of Parkinson's disease is associated with bulbar dopaminergic D2 activity after REM sleep deprivation.

    PubMed

    Rodrigues, Lais S; Targa, Adriano D S; Noseda, Ana Carolina D; Aurich, Mariana F; Da Cunha, Cláudio; Lima, Marcelo M S

    2014-01-01

    Olfactory and rapid eye movement (REM) sleep deficits are commonly found in untreated subjects with a recent diagnosis of Parkinson's disease (PD). Additionally, different studies report declines in olfactory performance during a short period of sleep deprivation. Mechanisms underlying these clinical manifestations are poorly understood, and impairment of dopamine (DA) neurotransmission in the olfactory bulb and the nigrostriatal pathway may have important roles in olfaction and REM sleep disturbances. Therefore, we hypothesized that modulation of the dopaminergic D2 receptors in the olfactory bulb could provide a more comprehensive understanding of the olfactory deficits in PD and REM sleep deprivation (REMSD). We decided to investigate the olfactory, neurochemical, and histological alterations generated through the administration of piribedil (a selective D2 agonist) or raclopride (a selective D2 antagonist) within the glomerular layer of the olfactory bulb, in rats subjected to intranigral rotenone and REMSD. Our findings provide evidence of the occurrence of a negative correlation (r = -0.52, P = 0.04) between the number of periglomerular TH-ir neurons and the bulbar levels of DA in the rotenone, but not sham, groups. A significant positive correlation (r = 0.34, P = 0.03) was observed between nigrostriatal DA levels and olfactory discrimination index (DI) for the sham groups, indicating that increased DA levels in the substantia nigra pars compacta (SNpc) are associated with enhanced olfactory discrimination performance. Also, increased levels in bulbar and striatal DA were induced by piribedil in the rotenone control and rotenone REMSD groups, consistent with reductions in the DI. The present evidence reinforce the idea that DA produced by periglomerular neurons, particularly the bulbar dopaminergic D2 receptors, is an essential participant in olfactory discrimination processes, as the SNpc, and the striatum.

  7. Quantification of muscle activity during sleep for patients with neurodegenerative diseases.

    PubMed

    Hanif, Umaer; Trap, Lotte; Jennum, Poul; Zoetmulder, Marielle; Sorensen, Helge B D

    2015-01-01

    Idiopathic REM sleep behavior disorder (iRBD) is a very strong predictor for later development of Parkinson's disease (PD), and is characterized by REM sleep without atonia (RSWA), resulting in increased muscle activity during REM sleep. Abundant studies have shown the loss of atonia during REM sleep, but our aim was to investigate whether iRBD and PD patients have increased muscle activity in both REM and NREM sleep compared to healthy controls. This was achieved by developing a semi-automatic algorithm for quantification of mean muscle activity per second during all sleep stages for the enrolled patients. The three groups examined included patients suffering from iRBD, PD and healthy control subjects (CO). To determine muscle activity, a baseline and threshold were established after pre-processing of the raw surface electromyography (sEMG) signal. The signal was then segmented according to the different sleep stages and muscle activity beyond the threshold was counted. The results were evaluated statistically using the two-sided Mann-Whitney U-test. The results suggested that iRBD patients also exhibit distinctive muscle activity characteristics in NREM sleep, however not as evident as in REM sleep, leading to the conclusion that RSWA still is the most distinct characteristic of RBD. Furthermore, the muscle activity of PD patients was comparable to that of controls with only slightly elevated amplitudes. PMID:26737659

  8. Subthreshold excitatory activity and motoneuron discharge during REM periods of active sleep.

    PubMed

    Chase, M H; Morales, F R

    1983-09-16

    A striking paradox of the rapid eye movement periods of active sleep, which are typically characterized by the exacerbation of somatomotor atonia, is the occurrence of muscle twitches and jerks. The purpose of this study was to examine the specific motoneuron membrane potential processes responsible for these myoclonic patterns of activity. In lumbar motoneurons, examined intracellularly in the cat prepared for long-term study, these processes consisted of recurrent depolarizing membrane potential shifts and spontaneous action potentials that were either full-sized or of partial amplitude. In addition, the invasion of antidromically induced spikes into the soma was often blocked. Hyperpolarizing potentials were evident in the intervals between spontaneous spikes. Hyperpolarization was also observed immediately before depolarization and spike activity, in contrast to the gradual depolarization of the motoneuron membrane potential that always occurred during wakefulness. Thus, during rapid eye movement periods, in conjunction with muscle twitches and jerks, a strong excitatory input is superimposed on a background of inhibitory input. The unique patterns of membrane potential change that arise thus seem to result from the simultaneous coactivation of excitatory and inhibitory processes. PMID:6310749

  9. The beneficial effects of leptin on REM sleep deprivation-induced cognitive deficits in mice.

    PubMed

    Chang, Hsiao-Fu; Su, Chun-Lin; Chang, Chih-Hua; Chen, Yu-Wen; Gean, Po-Wu

    2013-05-17

    Leptin, a 167 amino acid peptide, is synthesized predominantly in the adipose tissues and plays a key role in the regulation of food intake and body weight. Recent studies indicate that leptin receptor is expressed with high levels in many brain regions that may regulate synaptic plasticity. Here we show that deprivation of rapid eye movement (REMD) sleep resulted in impairment of both cue and contextual fear memory. In parallel, surface expression of GluR1 was reduced in the amygdala. Intraperitoneal injection of leptin to the REMD mice rescued memory impairment and reversed surface GluR1 reduction. Using whole-cell recording to evaluate the synaptic function of the thalamus-lateral amygdala (LA) pathway, we found a decrease in frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) concomitant with reduced AMPA/NMDA ratios in the REMD mice. By contrast, paired-pulse facilitation (PPF) was increased. The effects of REMD on mEPSCs and AMPA/NMDA ratio could be reversed by leptin treatment, whereas on PPR it could not. Phosphatase and tensin homolog (PTEN), a dual protein/lipid phosphatase, down-regulates the effect of the PI-3 kinase pathway. Fear conditioning increased whereas REMD led to a decrease in the phosphorylated states of PTEN, Akt, and glycogen synthase kinase-3β (GSK3β), and the effects of REMD were reversed by leptin. These results suggest that both pre- and postsynaptic functions of the thalamus-LA pathway were altered by fear conditioning and REMD in opposite directions. Leptin treatment reversed REMD-induced memory deficits primarily by a postsynaptic action by restoring surface expression of GluR1 without affecting PPR.

  10. Cholinergic and noncholinergic brainstem neurons expressing Fos after paradoxical (REM) sleep deprivation and recovery.

    PubMed

    Verret, Laure; Léger, Lucienne; Fort, Patrice; Luppi, Pierre-Hervé

    2005-05-01

    It is well accepted that populations of neurons responsible for the onset and maintenance of paradoxical sleep (PS) are restricted to the brainstem. To localize the structures involved and to reexamine the role of mesopontine cholinergic neurons, we compared the distribution of Fos- and choline acetyltransferase-labelled neurons in the brainstem of control rats, rats selectively deprived of PS for approximately 72 h and rats allowed to recover from such deprivation. Only a few cholinergic neurons from the laterodorsal (LDTg) and pedunculopontine tegmental nuclei were Fos-labelled after PS recovery. In contrast, a large number of noncholinergic Fos-labelled cells positively correlated with the percentage of time spent in PS was observed in the LDTg, sublaterodorsal, alpha and ventral gigantocellular reticular nuclei, structures known to contain neurons specifically active during PS. In addition, a large number of Fos-labelled cells were seen after PS rebound in the lateral, ventrolateral and dorsal periaqueductal grey, dorsal and lateral paragigantocellular reticular nuclei and the nucleus raphe obscurus. Interestingly, half of the cells in the latter nucleus were immunoreactive to choline acetyltransferase. In contrast to the well-accepted hypothesis, our results strongly suggest that neurons active during PS, recorded in the mesopontine cholinergic nuclei, are in the great majority noncholinergic. Our findings further demonstrate that many brainstem structures not previously identified as containing neurons active during PS contain cholinergic or noncholinergic neurons active during PS, and these structures may therefore play a key role during this state. Altogether, our results open a new avenue of research to identify the specific role of the populations of neurons revealed, their interrelations and their neurochemical identity.

  11. Substance P in the descending cholinergic projection to REM sleep-induction regions of the rat pontine reticular formation: anatomical and electrophysiological analyses.

    PubMed

    Kohlmeier, Kristi A; Burns, Joan; Reiner, Peter B; Semba, Kazue

    2002-01-01

    Release of acetylcholine within the pontine reticular formation (PRF) from the axon terminals of mesopontine cholinergic neurons has long been hypothesized to play an important role in rapid eye movement (REM) sleep generation. As some of these cholinergic neurons are known to contain substance P (SP), we used anatomical, electrophysiological and pharmacological techniques to characterize this projection in the rat. Double immunofluorescence demonstrated that 16% of all cholinergic neurons within the mesopontine tegmentum contained SP; this percentage increased to 27% in its caudal regions. When double immunofluorescence was combined with retrograde tracing techniques, it was observed that up to 11% of all SP-containing cholinergic neurons project to the PRF. Whole-cell patch-clamp recordings from in vitro brainstem slices revealed that SP administration depolarized or evoked an inward current in a dose-dependent manner in all PRF neurons examined, and that these effects were antagonized by a SP antagonist. The amplitude of the SP-induced inward current varied with changes in the Na+ concentration, did not reverse at the calculated K+ or Cl- equilibrium potentials, and was not attenuated in the presence of tetrodotoxin, low Ca2+ concentration or caesium ions. These data suggest that activation of a tetrodotoxin-insensitive cation channel(s) permeable to Na+ is responsible for a SP-induced inward current at resting membrane potentials. The depolarizing actions of SP appeared to be primarily due to activation of the adenylate cyclase pathway, and were additive with cholinergic receptor activation even at maximal concentrations. These data indicate that SP is colocalized in a subpopulation of mesopontine tegmental cholinergic neurons projecting to REM sleep-induction regions of the PRF, and that actions of these two neuroactive substances on PRF neurons are additive. If SP is coreleased with acetylcholine, the additive actions of the two neurotransmitters might

  12. An association analysis of HLA-DQB1 with narcolepsy without cataplexy and idiopathic hypersomnia with/without long sleep time in a Japanese population

    PubMed Central

    Miyagawa, Taku; Toyoda, Hiromi; Kanbayashi, Takashi; Imanishi, Aya; Sagawa, Yohei; Kotorii, Nozomu; Kotorii, Tatayu; Hashizume, Yuji; Ogi, Kimihiro; Hiejima, Hiroshi; Kamei, Yuichi; Hida, Akiko; Miyamoto, Masayuki; Ikegami, Azusa; Wada, Yamato; Takami, Masanori; Fujimura, Yota; Tamura, Yoshiyuki; Omata, Naoto; Masuya, Yasuhiro; Kondo, Hideaki; Moriya, Shunpei; Furuya, Hirokazu; Kato, Mitsuhiro; Kojima, Hiroto; Kashiwase, Koichi; Saji, Hiroh; Khor, Seik-Soon; Yamasaki, Maria; Ishigooka, Jun; Wada, Yuji; Chiba, Shigeru; Yamada, Naoto; Okawa, Masako; Kuroda, Kenji; Kume, Kazuhiko; Hirata, Koichi; Uchimura, Naohisa; Shimizu, Tetsuo; Inoue, Yuichi; Honda, Yutaka; Mishima, Kazuo; Honda, Makoto; Tokunaga, Katsushi

    2015-01-01

    Narcolepsy without cataplexy (NA w/o CA) (narcolepsy type 2) is a lifelong disorder characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, but no cataplexy. In the present study, we examined the human leukocyte antigen HLA-DQB1 in 160 Japanese patients with NA w/o CA and 1,418 control subjects. Frequencies of DQB1*06:02 were significantly higher in patients with NA w/o CA compared with controls (allele frequency: 16.6 vs. 7.8%, P=1.1×10−7, odds ratio (OR)=2.36; carrier frequency: 31.3 vs. 14.7%, P=7.6×10−8, OR=2.64). Distributions of HLA-DQB1 alleles other than DQB1*06:02 were compared between NA w/o CA and narcolepsy with cataplexy (NA-CA) to assess whether the genetic backgrounds of the two diseases have similarities. The distribution of the HLA-DQB1 alleles in DQB1*06:02-negative NA w/o CA was significantly different from that in NA-CA (P=5.8×10−7). On the other hand, the patterns of the HLA-DQB1 alleles were similar between DQB1*06:02-positive NA w/o CA and NA-CA. HLA-DQB1 analysis was also performed in 186 Japanese patients with idiopathic hypersomnia (IHS) with/without long sleep time, but no significant associations were observed. PMID:27081540

  13. An association analysis of HLA-DQB1 with narcolepsy without cataplexy and idiopathic hypersomnia with/without long sleep time in a Japanese population.

    PubMed

    Miyagawa, Taku; Toyoda, Hiromi; Kanbayashi, Takashi; Imanishi, Aya; Sagawa, Yohei; Kotorii, Nozomu; Kotorii, Tatayu; Hashizume, Yuji; Ogi, Kimihiro; Hiejima, Hiroshi; Kamei, Yuichi; Hida, Akiko; Miyamoto, Masayuki; Ikegami, Azusa; Wada, Yamato; Takami, Masanori; Fujimura, Yota; Tamura, Yoshiyuki; Omata, Naoto; Masuya, Yasuhiro; Kondo, Hideaki; Moriya, Shunpei; Furuya, Hirokazu; Kato, Mitsuhiro; Kojima, Hiroto; Kashiwase, Koichi; Saji, Hiroh; Khor, Seik-Soon; Yamasaki, Maria; Ishigooka, Jun; Wada, Yuji; Chiba, Shigeru; Yamada, Naoto; Okawa, Masako; Kuroda, Kenji; Kume, Kazuhiko; Hirata, Koichi; Uchimura, Naohisa; Shimizu, Tetsuo; Inoue, Yuichi; Honda, Yutaka; Mishima, Kazuo; Honda, Makoto; Tokunaga, Katsushi

    2015-01-01

    Narcolepsy without cataplexy (NA w/o CA) (narcolepsy type 2) is a lifelong disorder characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, but no cataplexy. In the present study, we examined the human leukocyte antigen HLA-DQB1 in 160 Japanese patients with NA w/o CA and 1,418 control subjects. Frequencies of DQB1*06:02 were significantly higher in patients with NA w/o CA compared with controls (allele frequency: 16.6 vs. 7.8%, P=1.1×10(-7), odds ratio (OR)=2.36; carrier frequency: 31.3 vs. 14.7%, P=7.6×10(-8), OR=2.64). Distributions of HLA-DQB1 alleles other than DQB1*06:02 were compared between NA w/o CA and narcolepsy with cataplexy (NA-CA) to assess whether the genetic backgrounds of the two diseases have similarities. The distribution of the HLA-DQB1 alleles in DQB1*06:02-negative NA w/o CA was significantly different from that in NA-CA (P=5.8×10(-7)). On the other hand, the patterns of the HLA-DQB1 alleles were similar between DQB1*06:02-positive NA w/o CA and NA-CA. HLA-DQB1 analysis was also performed in 186 Japanese patients with idiopathic hypersomnia (IHS) with/without long sleep time, but no significant associations were observed.

  14. GABAergic and non-GABAergic thalamic, hypothalamic and basal forebrain projections to the ventral oral pontine reticular nucleus: their implication in REM sleep modulation.

    PubMed

    Rodrigo-Angulo, Margarita L; Heredero, Susana; Rodríguez-Veiga, Elisia; Reinoso-Suárez, Fernando

    2008-05-19

    The ventral part of the oral pontine reticular nucleus (vRPO) is a demonstrated site of brainstem REM-sleep generation and maintenance. The vRPO has reciprocal connections with structures that control other states of the sleep-wakefulness cycle, many situated in the basal forebrain and the diencephalon. Some of these connections utilize the inhibitory neurotransmitter GABA. The aim of the present work is to map the local origin of the basal forebrain and diencephalon projections to the vRPO whether GABAergic or non-GABAergic. A double-labelling technique combining vRPO injections of the neuronal tracer, cholera-toxin (CTB), with GAD-immunohistochemistry, was used for this purpose in adult cats. All of the numerous CTB-positive neurons in the reticular thalamic and dorsocaudal hypothalamic nuclei were double-labelled (CTB/GAD-positive) neurons. Approximately 15%, 14% and 16% of the CTB-positive neurons in the zona incerta and the dorsal and lateral hypothalamic areas are, respectively, CTB/GAD-positive neurons. However, only some double-labelled neurons were found in other hypothalamic nuclei with abundant CTB-positive neurons, such as the paraventricular nucleus, perifornical area and H1 Forel field. In addition, CTB-positive neurons were abundant in the central amygdaline nucleus, terminal stria bed nuclei, median preoptic nucleus, medial and lateral preoptic areas, dorsomedial and ventromedial hypothalamic nuclei, posterior hypothalamic area and periventricular thalamic nucleus. The GABAergic and non-GABAergic connections described here may be the morphological pillar through which these prosencephalic structures modulate, either by inhibiting or by exciting, the vRPO REM-sleep inducing neurons during the different sleep-wakefulness cycle states.

  15. Input source and strength influences overall firing phase of model hippocampal CA1 pyramidal cells during theta: relevance to REM sleep reactivation and memory consolidation.

    PubMed

    Booth, Victoria; Poe, Gina R

    2006-01-01

    In simulation studies using a realistic model CA1 pyramidal cell, we accounted for the shift in mean firing phase from theta cycle peaks to theta cycle troughs during rapid-eye movement (REM) sleep reactivation of hippocampal CA1 place cells over several days of growing familiarization with an environment (Brain Res 855:176-180). Changes in the theta drive phase and amplitude between proximal and distal dendritic regions of the cell modulated the theta phase of firing when stimuli were presented at proximal and distal dendritic locations. Stimuli at proximal dendritic sites (proximal to 100 microm from the soma) invoked firing with a significant phase preference at the depolarizing theta peaks, while distal stimuli (>290 microm from the soma) invoked firing at hyperpolarizing theta troughs. The input location-related phase preference depended on active dendritic conductances, a sufficient electrotonic separation between input sites and theta-induced subthreshold membrane potential oscillations in the cell. The simulation results predict that the shift in mean theta phase during REM sleep cellular reactivation could occur through potentiation of distal dendritic (temporo-ammonic) synapses and depotentiation of proximal dendritic (Schaffer collateral) synapses over the course of familiarization.

  16. REM, not incubation, improves creativity by priming associative networks

    PubMed Central

    Cai, Denise J.; Mednick, Sarnoff A.; Harrison, Elizabeth M.; Kanady, Jennifer C.; Mednick, Sara C.

    2009-01-01

    The hypothesized role of rapid eye movement (REM) sleep, which is rich in dreams, in the formation of new associations, has remained anecdotal. We examined the role of REM on creative problem solving, with the Remote Associates Test (RAT). Using a nap paradigm, we manipulated various conditions of prior exposure to elements of a creative problem. Compared with quiet rest and non-REM sleep, REM enhanced the formation of associative networks and the integration of unassociated information. Furthermore, these REM sleep benefits were not the result of an improved memory for the primed items. This study shows that compared with quiet rest and non-REM sleep, REM enhances the integration of unassociated information for creative problem solving, a process, we hypothesize, that is facilitated by cholinergic and noradrenergic neuromodulation during REM sleep. PMID:19506253

  17. Dopaminergic D2 receptor is a key player in the substantia nigra pars compacta neuronal activation mediated by REM sleep deprivation.

    PubMed

    Proença, Mariana B; Dombrowski, Patrícia A; Da Cunha, Claudio; Fischer, Luana; Ferraz, Anete C; Lima, Marcelo M S

    2014-01-01

    Currently, several studies addresses the novel link between sleep and dopaminergic neurotransmission, focusing most closely on the mechanisms by which Parkinson's disease (PD) and sleep may be intertwined. Therefore, variations in the activity of afferents during the sleep cycles, either at the level of DA cell bodies in the ventral tegmental area (VTA) and/or substantia nigra pars compacta (SNpc) or at the level of dopamine (DA) terminals in limbic areas may impact functions such as memory. Accordingly, we performed striatal and hippocampal neurochemical quantifications of DA, serotonin (5-HT) and metabolites of rats intraperitoneally treated with haloperidol (1.5 mg/kg) or piribedil (8 mg/kg) and submitted to REM sleep deprivation (REMSD) and sleep rebound (REB). Also, we evaluated the effects of REMSD on motor and cognitive parameters and SNpc c-Fos neuronal immunoreactivity. The results indicated that DA release was strongly enhanced by piribedil in the REMSD group. In opposite, haloperidol prevented that alteration. A c-Fos activation characteristic of REMSD was affected in a synergic manner by piribedil, indicating a strong positive correlation between striatal DA levels and nigral c-Fos activation. Hence, we suggest that memory process is severely impacted by both D2 blockade and REMSD and was even more by its combination. Conversely, the activation of D2 receptor counteracted such memory impairment. Therefore, the present evidence reinforce that the D2 receptor is a key player in the SNpc neuronal activation mediated by REMSD, as a consequence these changes may have direct impact for cognitive and sleep abnormalities found in patients with PD. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

  18. The beneficial effects of regular exercise on cognition in REM sleep deprivation: behavioral, electrophysiological and molecular evidence.

    PubMed

    Zagaar, Munder; Alhaider, Ibrahim; Dao, An; Levine, Amber; Alkarawi, Ahmed; Alzubaidy, Mariam; Alkadhi, Karim

    2012-03-01

    Inadequate sleep is prevalent in modern societies and is known to profoundly impair cognitive function. We examined the impact of 4 weeks of regular treadmill exercise on sleep deprivation induced spatial learning and memory, synaptic plasticity and related signaling molecules in area CA1 of the rat hippocampus. Rats were exercised on a treadmill and subsequently sleep-deprived for 24h using the modified multiple platform technique. Testing of learning and short-term memory performance in the radial arm water maze showed that although sedentary sleep deprived rats were severely impaired, exercised sleep deprived rats' performance was normal. Extracellular recording from area CA1 of anesthetized rats revealed that early phase LTP (E-LTP) was markedly impaired in the sedentary sleep deprived animals, but was normal in the exercised sleep deprived group. Additionally, immunoblot analysis of CA1 area before (basal) and after expression of E-LTP indicated that the significant down-regulation of the brain derived neurotrophic factor (BDNF) and phosphorylated calcium-calmodulin dependent protein kinase II (P-CaMKII) levels in sleep deprived animals was prevented by the regular exercise regimen. The results suggest that the regular exercise protocol prevents the sleep deprivation induced impairments in short-term memory and E-LTP by preventing deleterious changes in the basal and post-stimulation levels of P-CaMKII and BDNF associated with sleep deprivation.

  19. Electrophysiological characterization of neurons in the dorsolateral pontine REM sleep induction zone of the rat: intrinsic membrane properties and responses to carbachol and orexins

    PubMed Central

    Brown§, Ritchie E.; Winston, Stuart; Basheer, Radhika; Thakkar, Mahesh M; McCarley, Robert W.

    2006-01-01

    Pharmacological, lesion and single-unit recording techniques in several animal species have identified a region of the pontine reticular formation (Subcoeruleus, SubC) just ventral to the locus coeruleus as critically involved in the generation of rapid-eye-movement (REM) sleep. However, the intrinsic membrane properties and responses of SubC neurons to neurotransmitters important in REM sleep control, such as acetylcholine and orexins/hypocretins, have not previously been examined in any animal species and thus were targeted in this study. We obtained whole-cell patch-clamp recordings from visually identified SubC neurons in rat brain slices in vitro. Two groups of large neurons (mean diameter 30 and 27μm) were tentatively identified as cholinergic (rostral SubC) and noradrenergic (caudal SubC) neurons. SubC reticular neurons (non-cholinergic, non-noradrenergic) showed a medium-sized depolarizing sag during hyperpolarizing current pulses and often had a rebound depolarization (low-threshold spike, LTS). During depolarizing current pulses they exhibited little adaptation and fired maximally at 30–90 Hz. Those SubC reticular neurons excited by carbachol (n=27) fired spontaneously at 6 Hz, often exhibited a moderately sized LTS, and varied widely in size (17–42 μm). Carbachol-inhibited SubC reticular neurons were medium-sized (15–25 μm) and constituted two groups. The larger group (n=22) was silent at rest and possessed a prominent LTS and associated 1–4 action potentials. The second, smaller group (n=8) had a delayed return to baseline at the offset of hyperpolarizing pulses. Orexins excited both carbachol excited and carbachol inhibited SubC reticular neurons. SubC reticular neurons had intrinsic membrane properties and responses to carbachol similar to those described for other reticular neurons but a larger number of carbachol inhibited neurons were found (> 50 %), the majority of which demonstrated a prominent LTS and may correspond to PGO-on neurons

  20. High doses of systemic DHEA-sulfate do not affect sleep structure and elicit moderate changes in non-REM sleep EEG in rats.

    PubMed

    Schiffelholz, T; Holsboer, F; Lancel, M

    The hormone dehydroepiandrosterone (DHEA) and its metabolite DHEA-sulfate (DHEAS) occur in huge quantities in the plasma as well as in the brain of vertebrates. To investigate whether DHEAS modulates sleep-wake behavior, we assessed the sleep response to three doses (25, 50, and 100 mg/kg) of intraperitoneally administered DHEAS, mixed with oil, in 8 rats. DHEAS injections produced dose-dependent and long-lasting elevations in the plasma levels of both DHEAS and DHEA. DHEAS administration did not affect sleep time and architecture but exerted persistent effects on the electroencephalogram (EEG) within non-rapid eye movement sleep: 50 mg/kg DHEAS significantly augmented EEG power in the frequency range of sleep spindles, and 100 mg/kg DHEAS depressed EEG power in the slow-wave frequency bands. The findings indicate that DHEAS changes the sleep EEG in a dose-dependent way, possibly through a modulation of GABA- and glutamate-induced currents.

  1. Validation of non-REM sleep stage decoding from resting state fMRI using linear support vector machines.

    PubMed

    Altmann, A; Schröter, M S; Spoormaker, V I; Kiem, S A; Jordan, D; Ilg, R; Bullmore, E T; Greicius, M D; Czisch, M; Sämann, P G

    2016-01-15

    A growing body of literature suggests that changes in consciousness are reflected in specific connectivity patterns of the brain as obtained from resting state fMRI (rs-fMRI). As simultaneous electroencephalography (EEG) is often unavailable, decoding of potentially confounding sleep patterns from rs-fMRI itself might be useful and improve data interpretation. Linear support vector machine classifiers were trained on combined rs-fMRI/EEG recordings from 25 subjects to separate wakefulness (S0) from non-rapid eye movement (NREM) sleep stages 1 (S1), 2 (S2), slow wave sleep (SW) and all three sleep stages combined (SX). Classifier performance was quantified by a leave-one-subject-out cross-validation (LOSO-CV) and on an independent validation dataset comprising 19 subjects. Results demonstrated excellent performance with areas under the receiver operating characteristics curve (AUCs) close to 1.0 for the discrimination of sleep from wakefulness (S0|SX), S0|S1, S0|S2 and S0|SW, and good to excellent performance for the classification between sleep stages (S1|S2:~0.9; S1|SW:~1.0; S2|SW:~0.8). Application windows of fMRI data from about 70 s were found as minimum to provide reliable classifications. Discrimination patterns pointed to subcortical-cortical connectivity and within-occipital lobe reorganization of connectivity as strongest carriers of discriminative information. In conclusion, we report that functional connectivity analysis allows valid classification of NREM sleep stages. PMID:26596551

  2. Blockade of the NMDA and AMPA/kainate receptors in the dorsal raphe nucleus prevents the 5-HT₃ receptor agonist m-chlorophenylbiguanide-induced suppression of REM sleep in the rat.

    PubMed

    Monti, Jaime M; Jantos, Héctor; Catenaccio, Valentina; Xavier, Silvia

    2011-07-01

    The effects of the selective 5-HT(3) receptor agonist m-chlorophenylbiguanide (m-CPBG), and of the NMDA (N-methyl-D-aspartate) and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate)/kainate antagonists AP-5 [(±)-2-amino-5-phosphono-pentanoic acid] and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), respectively, were studied in adult male Wistar rats implanted for chronic sleep recordings. The compounds were microinjected directly into the dorsal raphe nucleus (DRN) during the light period of the 12-h light/12-h dark cycle. Infusion of m-CPBG (2 and 4mM) into the DRN induced a significant reduction of rapid-eye-movement sleep (REMS) and of the number of REM periods. Local infusion of AP-5 (0.5-1 mM) and CNQX (2 mM) significantly increased slow wave sleep (SWS). Pretreatment with AP-5 (0.5 mM) or CNQX (0.5 mM) antagonized the m-CPBG-induced suppression of REMS. It is proposed that the reduction of REMS after microinjection of m-CPBG into de DRN is related to the activation of glutamatergic interneurons that express the 5-HT(3) receptor and make synaptic contacts with serotonergic cells. The resultant increase of serotonin release at postsynaptic sites involved in the induction of REMS would provoke the suppression of the behavioral state. Our findings provide, in addition, new details concerning the pharmacology of DRN serotonergic neurons in the rat that may become relevant to the development of drugs for enhancing cortical and subcortical serotonergic neurotransmission.

  3. A study of the interrupted REM episode.

    PubMed

    Merica, H; Gaillard, J M

    1991-12-01

    Brief interruptions of REM sleep are considered to be part of the REM episode. The maximum allowable duration of such an interruption, which is used to define the end of the REM episode, is currently a matter of debate. Making measurements on individual REM cycles, inter-REM interval analysis was carried out to determine whether the generally adopted 15 minute empirical rule for this maximum needs to be extended to 25 minutes as suggested by several including Kobayashi et al. Our results show that there is no reason to alter the 15 minute rule and that measurements which do not take into account the time-of-night effect may be misleading. The proportion of interrupted REM episodes observed in our population of healthy adults is high. We have therefore also examined in some detail the phenomenology of the temporal evolution of the structure and content of the interrupted REM episodes. Both showed a definite change over the night: the interruptions in the earlier episodes tend to return the system to slow wave sleep while those in the later episodes tend to return it to wake. It is hypothesized that these interruptions reflect a measure of REM sleep pressure and its interaction with both slow wave sleep and wake pressures. PMID:1798770

  4. Mammalian sleep

    NASA Astrophysics Data System (ADS)

    Staunton, Hugh

    2005-05-01

    This review examines the biological background to the development of ideas on rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its relation to dreaming. Aspects of the phenomenon which are discussed include physiological changes and their anatomical location, the effects of total and selective sleep deprivation in the human and animal, and REM sleep behavior disorder, the latter with its clinical manifestations in the human. Although dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human, there is a contingent relation between REM sleep and dreaming. Thus, REM is taken as a marker for dreaming and as REM is distributed ubiquitously throughout the mammalian class, it is suggested that other mammals also dream. It is suggested that the overall function of REM sleep/dreaming is more important than the content of the individual dream; its function is to place the dreamer protagonist/observer on the topographical world. This has importance for the developing infant who needs to develop a sense of self and separateness from the world which it requires to navigate and from which it is separated for long periods in sleep. Dreaming may also serve to maintain a sense of ‘I’ness or “self” in the adult, in whom a fragility of this faculty is revealed in neurological disorders.

  5. Ostriches Sleep like Platypuses

    PubMed Central

    Lesku, John A.; Meyer, Leith C. R.; Fuller, Andrea; Maloney, Shane K.; Dell'Omo, Giacomo

    2011-01-01

    Mammals and birds engage in two distinct states of sleep, slow wave sleep (SWS) and rapid eye movement (REM) sleep. SWS is characterized by slow, high amplitude brain waves, while REM sleep is characterized by fast, low amplitude waves, known as activation, occurring with rapid eye movements and reduced muscle tone. However, monotremes (platypuses and echidnas), the most basal (or ‘ancient’) group of living mammals, show only a single sleep state that combines elements of SWS and REM sleep, suggesting that these states became temporally segregated in the common ancestor to marsupial and eutherian mammals. Whether sleep in basal birds resembles that of monotremes or other mammals and birds is unknown. Here, we provide the first description of brain activity during sleep in ostriches (Struthio camelus), a member of the most basal group of living birds. We found that the brain activity of sleeping ostriches is unique. Episodes of REM sleep were delineated by rapid eye movements, reduced muscle tone, and head movements, similar to those observed in other birds and mammals engaged in REM sleep; however, during REM sleep in ostriches, forebrain activity would flip between REM sleep-like activation and SWS-like slow waves, the latter reminiscent of sleep in the platypus. Moreover, the amount of REM sleep in ostriches is greater than in any other bird, just as in platypuses, which have more REM sleep than other mammals. These findings reveal a recurring sequence of steps in the evolution of sleep in which SWS and REM sleep arose from a single heterogeneous state that became temporally segregated into two distinct states. This common trajectory suggests that forebrain activation during REM sleep is an evolutionarily new feature, presumably involved in performing new sleep functions not found in more basal animals. PMID:21887239

  6. Sleep Disorders (PDQ)

    MedlinePlus

    ... The two main phases of sleep are rapid eye movement (REM) and non-rapid eye movement (NREM): REM sleep, also known as "dream sleep," ... taken during sleep that show: Brain wave changes. Eye movements. Breathing rate. Blood pressure . Heart rate and electrical ...

  7. A quantitative study of the brainstem cholinergic projections to the ventral part of the oral pontine reticular nucleus (REM sleep induction site) in the cat.

    PubMed

    Rodrigo-Angulo, Margarita Lucía; Rodríguez-Veiga, Elisia; Reinoso-Suárez, Fernando

    2005-01-01

    The ventral part of the cat oral pontine reticular nucleus (vRPO) is the site in which microinjections of small dose and volume of cholinergic agonists produce long-lasting rapid eye movement sleep with short latency. The present study determined the precise location and proportions of the cholinergic brainstem neuronal population that projects to the vRPO using a double-labeling method that combines the neuronal tracer horseradish peroxidase-wheat germ agglutinin with choline acetyltransferase immunocytochemistry in cats. Our results show that 88.9% of the double-labeled neurons in the brainstem were located, noticeably bilaterally, in the cholinergic structures of the pontine tegmentum. These neurons occupied not only the pedunculopontine and laterodorsal tegmental nuclei, which have been described to project to other pontine tegmentum structures, but also the locus ceruleus complex principally the locus ceruleus alpha and peri-alpha, and the parabrachial nuclei. Most double-labeled neurons were found in the pedunculopontine tegmental nucleus and locus ceruleus complex and, much less abundantly, in the laterodorsal tegmental nucleus and the parabrachial nuclei. The proportions of these neurons among all choline acetyltransferase positive neurons within each structure were highest in the locus ceruleus complex, followed in descending order by the pedunculopontine and laterodorsal tegmental nuclei and then, the parabrachial nuclei. The remaining 11.1% of double-labeled neurons were found bilaterally in other cholinergic brainstem structures: around the oculomotor, facial and masticatory nuclei, the caudal pontine tegmentum and the praepositus hypoglossi nucleus. The disperse origins of the cholinergic neurons projecting to the vRPO, in addition to the abundant noncholinergic afferents to this nucleus may indicate that cholinergic stimulation is not the only or even the most decisive event in the generation of REM sleep.

  8. A new function of rapid eye movement sleep: improvement of muscular efficiency.

    PubMed

    Cai, Zi-Jian

    2015-05-15

    Previously I demonstrated that the slow wave sleep (SWS) functioned to adjust the emotional balance disrupted by emotional memories randomly accumulated during waking, while the rapid eye movement (REM) sleep played the opposite role. Many experimental results have unambiguously shown that various emotional memories are processed during REM sleep. In this article, it is attempted to combine this confirmed function of REM sleep with the atonic state unique to REM sleep, and to integrate a new theory suggesting that improvement of muscular efficiency be a new function of REM sleep. This new function of REM sleep is more advantageous than the function of REM sleep in emotional memories and disinhibited drives to account for the phylogenetic variations of REM sleep, especially the absence of REM sleep in dolphins and short duration of REM sleep in birds in contrary to that in humans and rodents, the absence of penile erections in REM sleep in armadillo, as well as the higher voltage in EEG during REM sleep in platypus and ostrich. Besides, this new function of REM sleep is also advantageous to explain the association of REM sleep with the atonic episodes in SWS, the absence of drastic menopausal change in duration of REM sleep, and the effects of ambient temperature on the duration of REM sleep. These comparative and experimental evidences support the improvement of muscular efficiency as a new and major function of REM sleep. PMID:25770701

  9. Contribution of REM sleep to Fos and FRA expression in the vestibular nuclei of rat leading to vestibular adaptation during the STS-90 Neurolab Mission.

    PubMed

    Pompeiano, O

    2007-01-01

    1. Electrophysical studies performed in ground-based experiments have shown that VN neurons respond to labyrinthine signals following stimulation of macular gravity receptors. Additional evidence indicates that VN neurons may also respond to extralabyrinthine signals of pontine origin, which occur during the PGO waves typical of REM sleep (Bizzi et al., 1964a, b; cf. also Pompeiano, 1967, 1970, 1974 for ref.). 2. In a previous study (Pompeiano et al., 2002) changes in Fos and FRA expression were used to identify the short-term (Fos) and the long-term (FRA) molecular changes which affect the VN neurons at different time points of the space flight. In particular, while Fos protein persists in the brain tissue only for a few hours (6-8 hrs) after its induction, FRA proteins, which can also be induced in the same experimental conditions, persist in the brain tissue for longer periods of time (i.e. from 12/24 hrs to days). 3. In order to relate the changes in gene expression which occurred in the VN during the space flight either to gravity changes or to REM sleep, we investigated in a recent study (Centini et al, 2006) the changes in Fos and FRA expression which occurred in different phases of the sleep-waking cycle, thus being indicative of the animal state. We could then compare the results obtained during the space lab Mission with those previously observed either in ground-based experiments during the physiological state of waking and slow-wave (SWS) or during neurochemically induced episodes of PS, as obtained after microinjection of appropriate agents in dorsal pontine structures of rats. 4. Our findings indicated that a waking state possibly associated with episodes of SWS, occurred at FD2 and FD14, i.e. at launch and after exposure of the animal to microgravity. It appeared also that at the reentry (R + 1) rather than at launch (FD2), an increase in Fos and FRA expression affected the noradrenergic LC neurons, as well as several related structures. These

  10. Sleep

    MedlinePlus

    ... sleep deprivation? What are sleep myths? What are sleep disorders? Can certain diseases/conditions disrupt sleep? What is ... sleep deprivation? What are sleep myths? What are sleep disorders? Can certain diseases/conditions disrupt sleep? What is ...

  11. Dream Recall Frequencies and Dream Content in Wilson's Disease with and without REM Sleep Behaviour Disorder: A Neurooneirologic Study

    PubMed Central

    Trindade, Mateus C.; Schredl, Michael; Pires, Joana; Reinhard, Iris; Bittencourt, Thais; Lorenzi-Filho, Geraldo; Alves, Rosana Cardoso; de Andrade, Daniel Ciampi; Fonoff, Erich T.; Bor-Seng-Shu, Edson; Machado, Alexandre A.; Teixeira, Manoel J.; Barbosa, Egberto R.

    2016-01-01

    Objective. Violent dream content and its acting out during rapid eye movement sleep are considered distinctive for rapid eye movement sleep behaviour disorder (RBD). This study reports first quantitative data on dreaming in a cohort of patients with treated Wilson's disease (WD) and in patients with WD with RBD. Methods. Retrospective questionnaires on different dimensions of dreaming and a prospective two-week home dream diary with self-rating of emotions and blinded, categorical rating of content by an external judge. Results. WD patients showed a significantly lower dream word count and very few other differences in dream characteristics compared to age- and sex-matched healthy controls. Compared to WD patients without RBD, patients with WD and RBD reported significantly higher nightmare frequencies and more dreams with violent or aggressive content retrospectively; their prospectively collected dream reports contained significantly more negative emotions and aggression. Conclusions. The reduction in dream length might reflect specific cognitive deficits in WD. The lack of differences regarding dream content might be explained by the established successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance with the current definition of RBD, violent, aggressive dream content seems to be a characteristic of RBD also in WD. PMID:27051076

  12. Dream Recall Frequencies and Dream Content in Wilson's Disease with and without REM Sleep Behaviour Disorder: A Neurooneirologic Study.

    PubMed

    Tribl, Gotthard G; Trindade, Mateus C; Schredl, Michael; Pires, Joana; Reinhard, Iris; Bittencourt, Thais; Lorenzi-Filho, Geraldo; Alves, Rosana Cardoso; de Andrade, Daniel Ciampi; Fonoff, Erich T; Bor-Seng-Shu, Edson; Machado, Alexandre A; Teixeira, Manoel J; Barbosa, Egberto R

    2016-01-01

    Objective. Violent dream content and its acting out during rapid eye movement sleep are considered distinctive for rapid eye movement sleep behaviour disorder (RBD). This study reports first quantitative data on dreaming in a cohort of patients with treated Wilson's disease (WD) and in patients with WD with RBD. Methods. Retrospective questionnaires on different dimensions of dreaming and a prospective two-week home dream diary with self-rating of emotions and blinded, categorical rating of content by an external judge. Results. WD patients showed a significantly lower dream word count and very few other differences in dream characteristics compared to age- and sex-matched healthy controls. Compared to WD patients without RBD, patients with WD and RBD reported significantly higher nightmare frequencies and more dreams with violent or aggressive content retrospectively; their prospectively collected dream reports contained significantly more negative emotions and aggression. Conclusions. The reduction in dream length might reflect specific cognitive deficits in WD. The lack of differences regarding dream content might be explained by the established successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance with the current definition of RBD, violent, aggressive dream content seems to be a characteristic of RBD also in WD. PMID:27051076

  13. Dream Recall Frequencies and Dream Content in Wilson's Disease with and without REM Sleep Behaviour Disorder: A Neurooneirologic Study.

    PubMed

    Tribl, Gotthard G; Trindade, Mateus C; Schredl, Michael; Pires, Joana; Reinhard, Iris; Bittencourt, Thais; Lorenzi-Filho, Geraldo; Alves, Rosana Cardoso; de Andrade, Daniel Ciampi; Fonoff, Erich T; Bor-Seng-Shu, Edson; Machado, Alexandre A; Teixeira, Manoel J; Barbosa, Egberto R

    2016-01-01

    Objective. Violent dream content and its acting out during rapid eye movement sleep are considered distinctive for rapid eye movement sleep behaviour disorder (RBD). This study reports first quantitative data on dreaming in a cohort of patients with treated Wilson's disease (WD) and in patients with WD with RBD. Methods. Retrospective questionnaires on different dimensions of dreaming and a prospective two-week home dream diary with self-rating of emotions and blinded, categorical rating of content by an external judge. Results. WD patients showed a significantly lower dream word count and very few other differences in dream characteristics compared to age- and sex-matched healthy controls. Compared to WD patients without RBD, patients with WD and RBD reported significantly higher nightmare frequencies and more dreams with violent or aggressive content retrospectively; their prospectively collected dream reports contained significantly more negative emotions and aggression. Conclusions. The reduction in dream length might reflect specific cognitive deficits in WD. The lack of differences regarding dream content might be explained by the established successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance with the current definition of RBD, violent, aggressive dream content seems to be a characteristic of RBD also in WD.

  14. REM Restriction Persistently Alters Strategy Used to Solve a Spatial Task

    ERIC Educational Resources Information Center

    Bjorness, Theresa E.; Tysor, Michael K.; Poe, Gina R.; Riley, Brett T.

    2005-01-01

    We tested the hypothesis that rapid eye movement (REM) sleep is important for complex associative learning by restricting rats from entering REM sleep for 4 h either immediately after training on an eight-box spatial task (0-4 REMr) or 4 h following training (4-8 REMr). Both groups of REM-restricted rats eventually reached the same overall…

  15. The role of the melanoma gene MC1R in Parkinson disease and REM sleep behavior disorder.

    PubMed

    Gan-Or, Ziv; Mohsin, Noreen; Girard, Simon L; Montplaisir, Jacques Y; Ambalavanan, Amirthagowri; Strong, Stephanie; Mallett, Victoria; Laurent, Sandra B; Bourassa, Cynthia V; Boivin, Michel; Langlois, Melanie; Arnulf, Isabelle; Högl, Birgit; Frauscher, Birgit; Monaca, Christelle; Desautels, Alex; Gagnon, Jean-François; Postuma, Ronald B; Dion, Patrick A; Dauvilliers, Yves; Dupre, Nicolas; Alcalay, Roy N; Rouleau, Guy A

    2016-07-01

    The MC1R gene, suggested to be involved in Parkinson disease (PD) and melanoma, was sequenced in PD patients (n = 539) and controls (n = 265) from New York, and PD patients (n = 551), rapid eye movement sleep behavior disorder (RBD) patients (n = 351), and controls (n = 956) of European ancestry. Sixty-eight MC1R variants were identified, including 7 common variants with frequency > 0.01. None of the common variants was associated with PD or RBD in the different regression models. In a meta-analysis with fixed-effect model, the p.R160W variant was associated with an increased risk for PD (odds ratio = 1.22, 95% confidence interval = 1.02-1.47, p = 0.03) but with significant heterogeneity (p = 0.048). Removing one study that introduced the heterogeneity resulted in nonsignificant association (odds ratio = 1.11, 95% confidence interval, 0.92-1.35, p = 0.27, heterogeneity p = 0.57). Rare variants had similar frequencies in patients and controls (10.54% and 10.15%, respectively, p = 0.75), and no cumulative effect of carrying more than one MC1R variant was found. The present study does not support a role for the MC1R p.R160W and other variants in susceptibility for PD or RBD.

  16. The role of the melanoma gene MC1R in Parkinson disease and REM sleep behavior disorder.

    PubMed

    Gan-Or, Ziv; Mohsin, Noreen; Girard, Simon L; Montplaisir, Jacques Y; Ambalavanan, Amirthagowri; Strong, Stephanie; Mallett, Victoria; Laurent, Sandra B; Bourassa, Cynthia V; Boivin, Michel; Langlois, Melanie; Arnulf, Isabelle; Högl, Birgit; Frauscher, Birgit; Monaca, Christelle; Desautels, Alex; Gagnon, Jean-François; Postuma, Ronald B; Dion, Patrick A; Dauvilliers, Yves; Dupre, Nicolas; Alcalay, Roy N; Rouleau, Guy A

    2016-07-01

    The MC1R gene, suggested to be involved in Parkinson disease (PD) and melanoma, was sequenced in PD patients (n = 539) and controls (n = 265) from New York, and PD patients (n = 551), rapid eye movement sleep behavior disorder (RBD) patients (n = 351), and controls (n = 956) of European ancestry. Sixty-eight MC1R variants were identified, including 7 common variants with frequency > 0.01. None of the common variants was associated with PD or RBD in the different regression models. In a meta-analysis with fixed-effect model, the p.R160W variant was associated with an increased risk for PD (odds ratio = 1.22, 95% confidence interval = 1.02-1.47, p = 0.03) but with significant heterogeneity (p = 0.048). Removing one study that introduced the heterogeneity resulted in nonsignificant association (odds ratio = 1.11, 95% confidence interval, 0.92-1.35, p = 0.27, heterogeneity p = 0.57). Rare variants had similar frequencies in patients and controls (10.54% and 10.15%, respectively, p = 0.75), and no cumulative effect of carrying more than one MC1R variant was found. The present study does not support a role for the MC1R p.R160W and other variants in susceptibility for PD or RBD. PMID:27131830

  17. The lateral hypothalamic area controls paradoxical (REM) sleep by means of descending projections to brainstem GABAergic neurons.

    PubMed

    Clément, Olivier; Sapin, Emilie; Libourel, Paul-Antoine; Arthaud, Sébastien; Brischoux, Frédéric; Fort, Patrice; Luppi, Pierre-Hervé

    2012-11-21

    It has recently been shown that the ventrolateral part of the periaqueductal gray (VLPAG) and the adjacent dorsal deep mesencephalic nucleus (dDpMe) contain GABAergic neurons gating paradoxical sleep (PS) onset by means of their projection to the glutamatergic PS-on neurons of the sublaterodorsal tegmental nucleus (SLD). To determine the mechanisms responsible for the cessation of activity of these GABAergic PS-off neurons at the onset and during PS, we combined the immunostaining of c-FOS, a marker of neuronal activation, with cholera toxin b subunit (CTb) retrograde tracing from the VLPAG/dDpMe in three groups of rats (control, PS deprived, and PS hypersomniac). We found that the lateral hypothalamic area (LH) is the only brain structure containing a very large number of neurons activated during PS hypersomnia and projecting to the VLPAG/dDpMe. We further demonstrated that 44% of these neurons express the neuropeptide melanin concentrating hormone (MCH). We then showed that bilateral injections in the LH of two inhibitory compounds, clonidine (an α-2 adrenergic agonist) and muscimol (a GABAa agonist) induce an inhibition of PS. Furthermore, after muscimol injections in the LH, the VLPAG/dDpMe contained a large number of activated neurons, mostly GABAergic, and projecting to the SLD. Altogether, our results indicate for the first time that the activation of a population of LH neurons, in part MCH containing, is necessary for PS to occur. Furthermore, our results strongly suggest that these neurons trigger PS by means of their inhibitory projection to the PS-off GABAergic neurons located in the VLPAG/dDpMe.

  18. A very large number of GABAergic neurons are activated in the tuberal hypothalamus during paradoxical (REM) sleep hypersomnia.

    PubMed

    Sapin, Emilie; Bérod, Anne; Léger, Lucienne; Herman, Paul A; Luppi, Pierre-Hervé; Peyron, Christelle

    2010-07-26

    We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS) hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH) neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD(67) mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD(67)in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD(+), Fos-ir/MCH(+), and GAD(+)/MCH(+) double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD(+) neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis.

  19. Heterogeneous distribution of the serotonin 5-HT(1A) receptor mRNA in chemically identified neurons of the mouse rostral brainstem: Implications for the role of serotonin in the regulation of wakefulness and REM sleep.

    PubMed

    Bonnavion, Patricia; Bernard, Jean-François; Hamon, Michel; Adrien, Joëlle; Fabre, Veronique

    2010-07-15

    The 5-HT(1A) receptor (5-HT(1A)R) plays a key role in the inhibitory influence of serotonin (5-HT) on rapid eye movement (REM) sleep in rodents. However, the neuronal networks mediating such influence are mostly unknown, notably in the mouse. This led us to map 5-HT(1A)R mRNA, by in situ hybridization histochemistry (ISHH), and to characterize the neuronal phenotype of 5-HT(1A)R mRNA-positive neurons by dual ISHH and ISHH combined with immunohistochemistry, throughout the mouse rostral brainstem, a pivotal region for the generation of REM sleep and cortical activation. 5-HT(1A)R mRNA was found in most 5-HT neurons in the dorsal raphe (DR), the median raphe (MnR), the B9, and the interpeduncular (IP) nuclei. 5-HT(1A)R mRNA-positive neurons were also identified in individualized clusters of gamma-aminobutyric acid (GABA)ergic neurons in the DR and in neurons of an undetermined phenotype in the MnR. In addition, 1) GABAergic neurons of the ventral portion of Gudden's dorsal tegmental nucleus (DTg), the IP, and the caudal portion of the deep mesencephalic nucleus (DpMe), and 2) glutamatergic neurons scattered in the caudal pontine reticular nucleus (PnC) and densely packed in the internal lateral parabrachial subnucleus (PBil) also expressed 5-HT(1A)R mRNA. In contrast, no specific 5-HT(1A)R-related ISHH signal was generally detected in brainstem cholinergic and catecholaminergic neurons. These results emphasize the role of 5-HT(1A)R as an autoreceptor and the phenotypical heterogeneity of 5-HT(1A)R-expressing neurons within the DR and the MnR in the mouse brain. They also provide a neuroanatomical basis for understanding the influence of 5-HT(1A)R on REM sleep and wakefulness.

  20. Heightened sexual interest and sleep disturbance

    NASA Technical Reports Server (NTRS)

    Zarcone, V.; De La Pena, A.; Dement, W. C.

    1974-01-01

    The study demonstrates a behavioral effect of selective sleep disturbance in normal human subjects. Ten male subjects were selectively REM-deprived for two nights by awakening them at the onset of REM sleep. In addition, there were baseline and non-REM awakening conditions. Heightened sexual interest was defined by the number of film frames (using a Mackworth camera) in which subjects fixated on parts of the female figure in photographs. The largest mean difference in sexual interest was found between baseline and REM-deprivation. Both the non-REM awakenings and REM-sleep deprivation enhanced sexual interest. The failure to demonstrate a significant difference between REM-deprivation and non-REM awakenings may be due to the fact that subjects were REM-sleep-deprived in both conditions. It is suggested that REM-sleep loss may lead to increased selective attention and preoccupation with any cues which are usually interesting.

  1. Diagnosing Sleep Disorders | NIH MedlinePlus the Magazine

    MedlinePlus

    ... page please turn Javascript on. Feature: Are You Sleep-Deprived? Diagnosing Sleep Disorders Past Issues / Summer 2012 Table of Contents ... reach REM sleep during their naps. What are Sleep Studies? Sleep studies are tests that measure how ...

  2. The Impact of Sound on Electroencephalographic Waves during Sleep in Patients Suffering from Tinnitus.

    PubMed

    Pedemonte, Marisa; Testa, Martín; Díaz, Marcela; Suárez-Bagnasco, Diego

    2014-09-01

    Based on the knowledge that sensory processing continues during sleep and that a relationship exists between sleep and learning, a new strategy for treatment of idiopathic subjective tinnitus, consisted of customized sound stimulation presented during sleep, was tested. It has been previously shown that this treatment induces a sustained decrease in tinnitus intensity; however, its effect on brain activity has not yet been studied. In this work, we compared the impact of sound stimulation in tinnitus patients in the different sleep stages. Ten patients with idiopathic tinnitus were treated with sound stimulation mimicking tinnitus during sleep. Power spectra and intra- and inter-hemispheric coherence of electroencephalographic waves from frontal and temporal electrodes were measured with and without sound stimulation for each sleep stage (stages N2 with sleep spindles; N3 with slow wave sleep and REM sleep with Rapid Eye Movements). The main results found were that the largest number of changes, considering both the power spectrum and wave׳s coherence, occurred in stages N2 and N3. The delta and theta bands were the most changed, with important changes also in coherence of spindles during N2. All changes were more frequent in temporal areas. The differences between the two hemispheres do not depend, at least exclusively, on the side where the tinnitus is perceived and, hence, of the stimulated side. These results demonstrate that sound stimulation during sleep in tinnitus patients׳ influences brain activity and open an avenue for investigating the mechanism underlying tinnitus and its treatment.

  3. Chimpanzee sleep stages.

    NASA Technical Reports Server (NTRS)

    Freemon, F. R.; Mcnew, J. J.; Adey, W. R.

    1971-01-01

    The electroencephalogram and electro-oculogram of two unrestrained juvenile chimpanzees was monitored for 7 consecutive nights using telemetry methods. Of the sleeping time, 23% was spent in the rapid eye movement of REM type of sleep, whereas 8, 4, 15, and 10% were spent in non-REM stages 1 through 4, respectively. Seven to nine periods of REM sleep occurred per night. The average time from the beginning of one REM period to the beginning of the next was approximately 85 min.

  4. Monotremes and the evolution of rapid eye movement sleep.

    PubMed

    Siegel, J M; Manger, P R; Nienhuis, R; Fahringer, H M; Pettigrew, J D

    1998-07-29

    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.

  5. [Sleep psychiatry].

    PubMed

    Chiba, Shigeru

    2013-01-01

    Sleep disorders are serious issues in modern society. There has been marked scientific interest in sleep for a century, with the discoveries of the electrical activity of the brain (EEG), sleep-wake system, rapid eye movement (REM) sleep, and circadian rhythm system. Additionally, the advent of video-polysomnography in clinical research has revealed some of the consequences of disrupted sleep and sleep deprivation in psychiatric disorders. Decades of clinical research have demonstrated that sleep disorders are intimately tied to not only physical disease (e. g., lifestyle-related disease) but psychiatric illness. According to The International Classification of Sleep Disorders (2005), sleep disorders are classified into 8 major categories: 1) insomnia, 2) sleep-related breathing disorders, 3) hypersomnias of central origin, 4) circadian rhythm sleep disorders, 5) parasomnias, 6) sleep-related movement disorders, 7) isolated symptoms, and 8) other sleep disorders. Several sleep disorders, including obstructive sleep apnea syndrome, restless legs syndrome, periodic limb movement disorder, sleepwalking, REM sleep behavior disorder, and narcolepsy, may be comorbid or possibly mimic numerous psychiatric disorders, and can even occur due to psychiatric pharmacotherapy. Moreover, sleep disorders may exacerbate underlying psychiatric disorders when left untreated. Therefore, psychiatrists should pay attention to the intimate relationship between sleep disorders and psychiatric symptoms. Sleep psychiatry is an academic field focusing on interrelations between sleep medicine and psychiatry. This mini-review summarizes recent findings in sleep psychiatry. Future research on the bidirectional relation between sleep disturbance and psychiatric symptoms will shed light on the pathophysiological view of psychiatric disorders and sleep disorders. PMID:24050022

  6. Different sleep onset criteria at the multiple sleep latency test (MSLT): an additional marker to differentiate central nervous system (CNS) hypersomnias.

    PubMed

    Pizza, Fabio; Vandi, Stefano; Detto, Stefania; Poli, Francesca; Franceschini, Christian; Montagna, Pasquale; Plazzi, Giuseppe

    2011-03-01

    Excessive daytime sleepiness (EDS) has different correlates in non-rapid eye movement (NREM) [idiopathic hypersomnia (IH) without long sleep time] and REM sleep [narcolepsy without cataplexy (NwoC) and narcolepsy with cataplexy (NC)]-related hypersomnias of central origin. We analysed sleep onset characteristics at the multiple sleep latency test (MSLT) applying simultaneously two sleep onset criteria in 44 NC, seven NwoC and 16 IH consecutive patients referred for subjective EDS complaint. Sleep latency (SL) at MSLT was assessed both as the time elapsed to the occurrence of a single epoch of sleep Stage 1 NREM (SL) and of unequivocal sleep [three sleep Stage 1 NREM epochs or any other sleep stage epoch, sustained SL (SusSL)]. Idiopathic hypersomnia patients showed significantly (P<0.0001) longer SusSL than SL (7.7±2.5 versus 5.6±1.3 min, respectively) compared to NwoC (5.8±2.5 versus 5.3±2.2 min) and NC patients (4.1±3 versus 3.9±3 min). A mean difference threshold between SusSL and SL ≥27 s reached a diagnostic value to discriminate IH versus NC and NwoC sufferers (sensitivity 88%; specificity 82%). Moreover, NC patients showed better subjective sleepiness perception than NwoC and IH cases in the comparison between naps with or without sleep occurrence. Simultaneous application of the two widely used sleep onset criteria differentiates IH further from NC and NwoC patients: IH fluctuate through a wake-Stage 1 NREM sleep state before the onset of sustained sleep, while NC and NwoC shift abruptly into a sustained sleep. The combination of SusSL and SL determination at MSLT should be tested as an additional objective differential criterion for EDS disorders.

  7. Reverberation, Storage, and Postsynaptic Propagation of Memories during Sleep

    ERIC Educational Resources Information Center

    Ribeiro, Sidarta; Nicolelis, Miguel A. L.

    2004-01-01

    In mammals and birds, long episodes of nondreaming sleep ("slow-wave" sleep, SW) are followed by short episodes of dreaming sleep ("rapid-eye-movement" sleep, REM). Both SW and REM sleep have been shown to be important for the consolidation of newly acquired memories, but the underlying mechanisms remain elusive. Here we review…

  8. Visual hallucinations and pontine demyelination in a child: possible REM dissociation?

    PubMed

    Vita, Maria Gabriella; Batocchi, Anna Paola; Dittoni, Serena; Losurdo, Anna; Cianfoni, Alessandro; Stefanini, Maria Chiara; Vollono, Catello; Della Marca, Giacomo; Mariotti, Paolo

    2008-12-15

    An 11 year-old-boy acutely developed complex visual and acoustic hallucinations. Hallucinations, consisting of visions of a threatening, evil character of the Harry Potter saga, persisted for 3 days. Neurological and psychiatric examinations were normal. Ictal EEG was negative. MRI documented 3 small areas of hyperintense signal in the brainstem, along the paramedian and lateral portions of pontine tegmentum, one of which showed post-contrast enhancement. These lesions were likely of inflammatory origin, and treatment with immunoglobulins was started. Polysomnography was normal, multiple sleep latency test showed a mean sleep latency of 8 minutes, with one sleep-onset REM period. The pontine tegmentum is responsible for REM sleep regulation, and contains definite "REM-on" and "REM-off" regions. The anatomical distribution of the lesions permits us to hypothesize that hallucinations in this boy were consequent to a transient impairment of REM sleep inhibitory mechanisms, with the appearance of dream-like hallucinations during wake.

  9. Visual hallucinations and pontine demyelination in a child: possible REM dissociation?

    PubMed

    Vita, Maria Gabriella; Batocchi, Anna Paola; Dittoni, Serena; Losurdo, Anna; Cianfoni, Alessandro; Stefanini, Maria Chiara; Vollono, Catello; Della Marca, Giacomo; Mariotti, Paolo

    2008-12-15

    An 11 year-old-boy acutely developed complex visual and acoustic hallucinations. Hallucinations, consisting of visions of a threatening, evil character of the Harry Potter saga, persisted for 3 days. Neurological and psychiatric examinations were normal. Ictal EEG was negative. MRI documented 3 small areas of hyperintense signal in the brainstem, along the paramedian and lateral portions of pontine tegmentum, one of which showed post-contrast enhancement. These lesions were likely of inflammatory origin, and treatment with immunoglobulins was started. Polysomnography was normal, multiple sleep latency test showed a mean sleep latency of 8 minutes, with one sleep-onset REM period. The pontine tegmentum is responsible for REM sleep regulation, and contains definite "REM-on" and "REM-off" regions. The anatomical distribution of the lesions permits us to hypothesize that hallucinations in this boy were consequent to a transient impairment of REM sleep inhibitory mechanisms, with the appearance of dream-like hallucinations during wake. PMID:19110890

  10. Non-rapid eye movement sleep with low muscle tone as a marker of rapid eye movement sleep regulation

    PubMed Central

    Tinguely, Gilberte; Huber, Reto; Borbély, Alexander A; Achermann, Peter

    2006-01-01

    Background It was recently reported that epochs of non-REM sleep (NREMS) with low muscle tone represent a partial correlate of REM sleep (REMS). To further investigate this phenomenon, episodes of restricted night-time sleep (23:00 – 03.00h) and subsequent morning sleep (10:00 – 13:00h) were analysed. Results Epochs of NREMS with low muscle tone (NLMT) were identified. Their frequency was higher in morning sleep than in night sleep. At night, the latency to the first occurrence of NLMT showed a bimodal distribution with modes at sleep onset and close to REMS onset. In morning sleep, the distribution was unimodal with the mode at sleep onset. An episode of NLMT at sleep onset occurred in 35.5% of the night sleep episodes and in 60.9% of the morning sleep episodes without sleep onset REMS (SOREMS). Also SOREMS occurred predominantly in morning sleep. REMS episodes were longer and NREMS episodes shorter in morning sleep than in night sleep, whereas cycle duration did not differ. Simulating the time course of slow-wave activity revealed a close correspondence between empirical and computed values for night sleep, and some discrepancies for morning sleep. Conclusion The results provide further evidence that NREMS with low muscle tone is a marker of REMS regulation. NLMT at sleep onset may represent an early manifestation of REMS. PMID:16401347

  11. Sleep Studies of Adults with Severe or Profound Mental Retardation and Epilepsy.

    ERIC Educational Resources Information Center

    Espie, Colin A.; Paul, Audrey; McFie, Joyce; Amos, Pat; Hamilton, David; McColl, John H.; And Others

    1998-01-01

    A study of the sleep patterns of 28 people with severe or profound mental retardation and epilepsy found atypical sleep stages with significant depletion of REM sleep and a predominance of indiscriminate non-REM sleep. Sleep diaries completed by caregivers reveal lengthy sleep periods, especially among those with profound mental retardation.…

  12. Common Sleep Problems (For Teens)

    MedlinePlus

    ... stages 1, 2, 3, 4, and REM (rapid eye movement) sleep make up a sleep cycle . One complete ... person can wake up easily. During these stages, eye movements slow down and eventually stop, heart and breathing ...

  13. Isolated sleep paralysis elicited by sleep interruption.

    PubMed

    Takeuchi, T; Miyasita, A; Sasaki, Y; Inugami, M; Fukuda, K

    1992-06-01

    We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non-ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy. PMID:1621022

  14. Isolated sleep paralysis elicited by sleep interruption.

    PubMed

    Takeuchi, T; Miyasita, A; Sasaki, Y; Inugami, M; Fukuda, K

    1992-06-01

    We elicited isolated sleep paralysis (ISP) from normal subjects by a nocturnal sleep interruption schedule. On four experimental nights, 16 subjects had their sleep interrupted for 60 minutes by forced awakening at the time when 40 minutes of nonrapid eye movement (NREM) sleep had elapsed from the termination of rapid eye movement (REM) sleep in the first or third sleep cycle. This schedule produced a sleep onset REM period (SOREMP) after the interruption at a high rate of 71.9%. We succeeded in eliciting six episodes of ISP in the sleep interruptions performed (9.4%). All episodes of ISP except one occurred from SOREMP, indicating a close correlation between ISP and SOREMP. We recorded verbal reports about ISP experiences and recorded the polysomnogram (PSG) during ISP. All of the subjects with ISP experienced inability to move and were simultaneously aware of lying in the laboratory. All but one reported auditory/visual hallucinations and unpleasant emotions. PSG recordings during ISP were characterized by a REM/W stage dissociated state, i.e. abundant alpha electroencephalographs and persistence of muscle atonia shown by the tonic electromyogram. Judging from the PSG recordings, ISP differs from other dissociated states such as lucid dreaming, nocturnal panic attacks and REM sleep behavior disorders. We compare some of the sleep variables between ISP and non-ISP nights. We also discuss the similarities and differences between ISP and sleep paralysis in narcolepsy.

  15. Adenosine and sleep

    SciTech Connect

    Yanik, G.M. Jr.

    1987-01-01

    Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A/sub 1/ receptors, /sup 3/H-L-PIA binding was measured. The Bmax values for /sup 3/H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in /sup 3/H-L-PIA binding resulted from REM sleep deprivation and not from stress.

  16. Field dependence and the effect of REM deprivation on thirst.

    PubMed

    Koulack, D; De Koninck, J; Oczkowski, G

    1978-04-01

    Recently a number of studies have concerned the possible function of rapid eye movement (REM) sleep and the mastery of stress. The present study was designed to explore the possibility that REM sleep might play a function in reducing the potency of a stressful physiological stimulus, thirst, as well as the possibility that such a function might be specific to individuals falling at different points along the field-dependence dimension. While there was no difference between REM deprivation and non-REM awakening nights in subsequent morning thirst, there was a significant interaction between field dependence and night on morning thirst measures for 10 college students. These results are discussed in light of previous work on stylistic differences in dreaming and their possible role in adaptation to stress. PMID:208050

  17. Slow Wave Sleep and Long Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Whitmire, Alexandra; Orr, Martin; Arias, Diana; Rueger, Melanie; Johnston, Smith; Leveton, Lauren

    2012-01-01

    While ground research has clearly shown that preserving adequate quantities of sleep is essential for optimal health and performance, changes in the progression, order and /or duration of specific stages of sleep is also associated with deleterious outcomes. As seen in Figure 1, in healthy individuals, REM and Non-REM sleep alternate cyclically, with stages of Non-REM sleep structured chronologically. In the early parts of the night, for instance, Non-REM stages 3 and 4 (Slow Wave Sleep, or SWS) last longer while REM sleep spans shorter; as night progresses, the length of SWS is reduced as REM sleep lengthens. This process allows for SWS to establish precedence , with increases in SWS seen when recovering from sleep deprivation. SWS is indeed regarded as the most restorative portion of sleep. During SWS, physiological activities such as hormone secretion, muscle recovery, and immune responses are underway, while neurological processes required for long term learning and memory consolidation, also occur. The structure and duration of specific sleep stages may vary independent of total sleep duration, and changes in the structure and duration have been shown to be associated with deleterious outcomes. Individuals with narcolepsy enter sleep through REM as opposed to stage 1 of NREM. Disrupting slow wave sleep for several consecutive nights without reducing total sleep duration or sleep efficiency is associated with decreased pain threshold, increased discomfort, fatigue, and the inflammatory flare response in skin. Depression has been shown to be associated with a reduction of slow wave sleep and increased REM sleep. Given research that shows deleterious outcomes are associated with changes in sleep structure, it is essential to characterize and mitigate not only total sleep duration, but also changes in sleep stages.

  18. Intrathecal administration of a gap junction decoupler, an inhibitor of Na(+)-K(+)-2Cl(-) cotransporter 1, or a GABA(A) receptor agonist attenuates mechanical pain hypersensitivity induced by REM sleep deprivation in the rat.

    PubMed

    Wei, Hong; Hao, Bin; Huang, Jin-Lu; Ma, Ai-Niu; Li, Xin-Yan; Wang, Yong-Xiang; Pertovaara, Antti

    2010-12-01

    We studied the hypothesis that some of the spinal mechanisms that are involved in neuropathic hypersensitivity play a role in hypersensitivity induced by REM sleep deprivation (REMSD). Rats with a chronic intrathecal (i.t.) catheter had REMSD of 48h duration that induced hypersensitivity to mechanical stimulation. After REMSD, the animals were treated i.t. with carbenoxolone (a gap junction decoupler), bumetanide (a blocker of Na(+)-K(+)-2Cl(-) cotransporter 1 or NKCC1), muscimol (a GABA(A) receptor agonist), or pretreated intraperitoneally with minocycline (an inhibitor of microglia activation). Previously, all these treatments attenuated neuropathic hypersensitivity. Following REMSD, carbenoxolone, bumetanide and muscimol had a strong antihypersensitivity effect, whereas pretreatment with minocycline failed to prevent development of hypersensitivity. The results suggest that among spinal pain facilitatory mechanisms that are common to REMSD and neuropathy are NKCC1 blocker- and gap junction decoupler-reversible mechanisms. Moreover, there is a net pain inhibitory effect by spinal administration of an exogenous GABA(A) receptor agonist following REMSD as shown earlier in neuropathy. In contrast, activation of spinal microglia may not be as important for the development of hypersensitivity induced by REMSD as following nerve injury.

  19. Rapid eye movement sleep in breath holders.

    PubMed

    Kohyama, J; Hasegawa, T; Shimohira, M; Fukumizu, M; Iwakawa, Y

    2000-07-01

    One-night polysomnography was performed on seven subjects suffering from breath-holding spells, including one whose death was suggested to be a consequence of a breath-holding spell. The fatal case showed no rapid eye movements (REMs) during REM sleep, although he exhibited REMs during wakefulness. The average numbers of both REMs and bursts of REMs in REM sleep in the other six breath holders were significantly lower than those in age-matched controls. The breath holders showed no airway obstruction, desaturation, or sleep fragmentation. Since the rapid ocular activity in REM sleep is generated in the brain stem, we hypothesized that a functional brainstem disturbance is involved in the occurrence of breath-holding spells.

  20. Genetics of rapid eye movement sleep in humans

    PubMed Central

    Adamczyk, M; Ambrosius, U; Lietzenmaier, S; Wichniak, A; Holsboer, F; Friess, E

    2015-01-01

    The trait-like nature of electroencephalogram (EEG) is well established. Furthermore, EEG of wake and non-rapid eye movement (non-REM) sleep has been shown to be highly heritable. However, the genetic effects on REM sleep EEG microstructure are as yet unknown. REM sleep is of special interest since animal and human data suggest a connection between REM sleep abnormalities and the pathophysiology of psychiatric and neurological diseases. Here we report the results of a study in monozygotic (MZ) and dizygotic (DZ) twins examining the heritability of REM sleep EEG. We studied the architecture, spectral composition and phasic parameters of REM sleep and identified genetic effects on whole investigated EEG frequency spectrum as well as phasic REM parameters (REM density, REM activity and organization of REMs in bursts). In addition, cluster analysis based on the morphology of the EEG frequency spectrum revealed that the similarity among MZ twins is close to intra-individual stability. The observed strong genetic effects on REM sleep characteristics establish REM sleep as an important source of endophenotypes for psychiatric and neurological diseases. PMID:26151926