REM Sleep Deprivation Research Articles

REM sleep deprivation-induced noradrenaline stimulates neuronal and inhibits glial Na–K ATPase in rat brain: In vivo and in vitro studies

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 α1-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 α1-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.

REM Illumination: Memory Consolidation

REM Illumination: Memory Consolidation

Corrigendum to “Rapid eye movement sleep deprivation in post-critical period, adolescent rats alters the balance between inhibitory and excitatory mechanisms in visual cortex” [Neurosci. Lett. 393 (2006) 131–135

Corrigendum to “Rapid eye movement sleep deprivation in post-critical period, adolescent rats alters the balance between inhibitory and excitatory mechanisms in visual cortex” [Neurosci. Lett. 393 (2006) 131–135

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

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 48 h 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.

Losing Sleep Over Cancer

Losing Sleep Over Cancer

Stimulatory role of calcium in rapid eye movement sleep deprivation–induced noradrenaline-mediated increase in Na-K-ATPase activity in rat brain

Rapid eye movement (REM) sleep deprivation elevates noradrenaline level, which upon acting on alpha1-adrenoceptors increases Na-K-ATPase activity; however, the detailed intracellular mechanism of action was unknown. Since membrane integrity is crucial for maintaining Na-K-ATPase activity as well as ionic exchange and noradrenaline affects membrane lipid-peroxidation, we proposed that the deprivation might modulate membrane lipid-peroxidation, which would modulate intracellular ionic concentration and thereby increase Na-K-ATPase activity. Hence, in this in vivo and in vitro study, rats were deprived of REM sleep for 4 days by the flowerpot method and suitable control experiments were conducted. The deprivation simultaneously decreased membrane lipid-peroxidation as well as increased Na-K-ATPase activity by its dephosphorylation and all the effects were induced by noradrenaline. Further, in vitro experiments showed that hydrogen peroxide (H 2O 2)-induced enhanced lipid-peroxidation increased synaptosomal calcium (Ca 2+)-influx, which was also prevented by noradrenaline and nifidipine, an L-type Ca 2+-channel blocker. Additionally, both nifidipine and cyclopiazonic acid, which have opposite effects on intracellular Ca 2+-concentration, prevented deprivation induced increased Na-K-ATPase activity. We propose that REM sleep deprivation elevates noradrenaline level in the brain that acting on alpha1-adrenoceptor simultaneously reduces membrane lipid-peroxidation but activates phospholipase-C, resulting in closure of L-type Ca 2+-channel and releasing membrane bound Ca 2+; the latter then dephosphorylates Na-K-ATPase, the active form, causing its increased activity.

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

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 degrees C. EEG activity, hypothalamic temperature, and motor activity were studied during a 24-h exposure to Tas ranging from 10 degrees C to -10 degrees C and for 4 days during recovery. Laboratory of Physiological Regulation during the Wake-Sleep Cycle, Department of Human and General Physiology, Alma Mater Studiorum-University of Bologna. 24 male albino rats. Animals were implanted with electrodes for EEG recording and a thermistor to measure hypothalamic temperature. 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. 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.

Rapid eye movement (REM) sleep homeostatic regulatory processes in the rat: Changes in the sleep–wake stages and electroencephalographic power spectra

The aim of this study was to elucidate physiological processes that are involved in the homeostatic regulation of REM sleep. Adult rats were chronically instrumented with sleep–wake recording electrodes. Following post-surgical recovery, rats were habituated extensively for freely moving polygraphic recording conditions. On the first experimental recording day (baseline day, BLD), polygraphic signs of undisturbed sleep–wake activities were recorded for 4 h (between 11:00 AM and 3:00 PM). During the second experimental recording day (REM sleep deprivation day, RDD), rats were selectively deprived of REM sleep for the first 2 h and then allowed to have normal sleep–wake for the following 2 h. The results demonstrated that during the first 2 h, compared to BLD, RDD recordings exhibited 87.80% less time in REM sleep and 16% more time in non-REM (NREM) sleep. The total percentages of wakefulness remained comparable between the BLD and RDD. During the RDD, the mean number of REM sleep episodes was much higher than in the BLD, indicating increased REM sleep drive. Electroencephalographic (EEG) power spectral analysis revealed that selective REM sleep deprivation increased delta power but decreased theta power during the residual REM sleep. During the last 2 h, after REM sleep deprivation, rats spent 51% more time in REM sleep compared to the BLD. Also during this period, the number of REM sleep episodes with the shortest (5–30 s) and longest (> 120 s) duration increased during the RDD. These findings suggest that the REM sleep homeostatic process involves increased delta- and decreased theta-frequency wave activities in the cortical EEG.

Rapid eye movement sleep deprivation decreases long-term potentiation stability and affects some glutamatergic signaling proteins during hippocampal development

Development of the mammalian CNS requires formation and stabilization of neuronal circuits and synaptic connections. Sensory stimulation provided by the environment orchestrates neuronal circuit formation in the waking state. Endogenous sources of activation are also implicated in these processes. Accordingly we hypothesized that sleep, especially rapid eye movement sleep (REMS), the stage characterized by high neuronal activity that is more prominent in development than adulthood, provides endogenous stimulation, which, like sensory input, helps to stabilize and refine neuronal circuits during CNS development. Young (Y: postnatal day (PN) 16) and adolescent (A: PN44) rats were rapid eye movement sleep–deprived (REMSD) by gentle cage-shaking for only 4 h on 3 consecutive days (total 12 h). The effect of REMS deprivation in Y and A rats was tested 3–7 days after the last deprivation session (Y, PN21–25; A, PN49–53) and was compared with younger (immature, I, PN9–12) untreated, age-matched, treated and normal control groups. REMS deprivation negatively affected the stability of long-term potentiation (LTP) in Y but not A animals. LTP instability in Y-REMSD animals was similar to the instability in even the more immature, untreated animals. Utilizing immunoblots, we identified changes in molecular components of glutamatergic synapses known to participate in mechanisms of synaptic refinement and plasticity. Overall, N-methyl- d-aspartate receptor subunit 2B (NR2B), N-methyl- d-aspartate receptor subunit 2A, AMPA receptor subunit 1 (GluR1), postsynaptic density protein 95 (PSD-95), and calcium/calmodulin kinase II tended to be lower in Y REMSD animals (NR2B, GluR1 and PSD-95 were significantly lower) compared with controls, an effect not present in the A animals. Taken together, these data indicate that early-life REMS deprivation reduces stability of hippocampal neuronal circuits, possibly by hindering expression of mature glutamatergic synaptic components. The findings support a role for REMS in the maturation of hippocampal neuronal circuits.

Rapid Eye Movement Sleep Deprivation Contributes to Reduction of Neurogenesis in the Hippocampal Dentate Gyrus of the Adult Rat

The dentate gyrus (DG) of the adult hippocampus contains progenitor cells, which have potential to differentiate into neurons. Previously we reported that 96 hours of total sleep deprivation reduces neurogenesis in the DG of adult rats. Loss of either non-rapid eye movement (NREM) or rapid eye movement (REM) sleep could have contributed to the effect of total sleep deprivation. The present study assessed the effect of 4 days of REM sleep deprivation (REMD) on neurogenesis. REMD was achieved by brief treadmill movement initiated by automatic online detection of REM sleep. A yoked-control (YC) rat was placed in the same treadmill and experienced the identical movement regardless the stage of the sleep-wake cycle. The thymidine analog 5- bromo- 2'- deoxy-uridine and the intrinsic proliferation marker, Ki-67, were both used to label proliferating cells. Basic neurophysiology laboratory. Male Sprague-Dawley male rats (300-320 g). REM sleep was reduced by 85% in REMD rats and by 43% in YC, compared with cage control animals and by 79% in REMD rats compared with YC. NREM sleep and slow wave activity within NREM did not differ in REMD and YC groups. Cell proliferation was reduced by 63 % in REMD compared with YC rats, and by 82% and 51%, respectively, in REMD and YC rats compared with cage controls. Across all animals, cell proliferation exhibited a positive correlation with the percentage of REM sleep (r = 0.84, P < 0.001). Reduced cell proliferation in REMD rats was confirmed with the intrinsic proliferation marker, Ki-67. REMD also reduced the percentage of proliferating cells that later expressed a mature neuronal marker. The present findings support a hypothesis that REM sleep-associated processes facilitate proliferation of granule cells in the adult hippocampal DG.

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

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.

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

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.

Noradrenaline acting on α1-adrenoceptor mediates REM sleep deprivation-induced increased membrane potential in rat brain synaptosomes

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 α1-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 α1-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 α1-adrenoceptor.

Effects of REM deprivation and an NMDA agonist on the extinction of conditioned fear

Rapid eye movement sleep (REM) has been implicated in a number of learning and memory tasks. Previous research has demonstrated that REM deprivation impairs the development of extinction of conditioned fear responses. However, the neurobiological mechanisms of this effect remain unclear. The present study investigated the effects of systemic administration of d-cycloserine (DCS), an NMDA agonist, on the extinction of a conditioned fear response following 6 h of REM deprivation. In experiment 1, rats were administered DCS between fear training and REM deprivation. In experiment 2, rats were administered DCS prior to extinction training. The results of experiment 1 indicated that both DCS alone and REM deprivation alone impaired extinction learning. Administration of DCS to REM deprived animals partially, but not completely, reversed the deficit in extinction. The results of experiment 2 indicated that regardless of prior REM deprivation history, DCS facilitated extinction learning. The results provide further evidence for a role of REM in the extinction of cued fear learning and indicate that this effect appears to be partially mediated by NMDA-dependent mechanisms.

Dream-associated Behaviors Affecting Pregnant and Postpartum Women

Evaluate the prevalence and phenomenology of dream-associated behaviors affecting pregnant and postpartum mothers. Episodes consist of anxious dreams and nightmares about the new infant that are accompanied by complex behaviors (motor activity, speaking, expressing emotion). Three-group design (postpartum, pregnant, null gravida), self-report, and repeated measures. Pregnancy and postpartum groups: completion of questionnaires in hospital room within 48 hours of giving birth and home telephone interviews; null gravida group: completion of questionnaires and interview in person or by telephone. Two hundred seventy-three women in 3 groups: postpartum: n = 202 (mean age = 29.7 +/- 4.94 years; 95 primiparas, 107 multiparas); pregnant: n = 50 (mean age = 31.1 +/- 5.44 years); null gravida: n = 21 (mean age = 28.5 +/- 6.34 years). Subjects completed questionnaires about pregnancy and birth factors, personality, and sleep and participated in interviews concerning the prevalence of recent infant dreams and nightmares, associated behaviors, anxiety, depression, and other psychopathologic factors. Most women in all groups recalled dreams (88%-91%). Postpartum and pregnant women recalled infant dreams and nightmares with equal prevalence, but more postpartum women reported they contained anxiety (75%) and the infant in peril (73%) than did pregnant women (59%, P < 0.05 and 42%, P < 0.0001). More postpartum (63%) than pregnant (40%) women reported dream-associated behaviors (P < 0.01), but neither group differed from null gravida women (56%). This was due to different distributions over groups of the behavior subtypes. Motor activity was present in twice as many postpartum (57%) as pregnant (24%) or null gravida (25%) women (all P < 0.0001). Expressing emotion was more prevalent among null gravida (56%) than postpartum women (27%) (P < 0.05) but was not different from pregnant women (37%). Speaking was equally prevalent among the 3 groups (12%-19%). Behaviors were associated with nightmares, dream anxiety and, among postpartum women, post-awakening anxiety (41%), confusion (51%), and a need to check on the infant (60%). Primiparas and multiparas differed in dream and nightmare recall but not in prevalence of dream-associated behaviors. The prevalent occurrence of pregnancy and postpartum infant dreams and associated behaviors may reflect the pervasive emotional influence of maternal concerns or changes instigated by severe sleep disruption, rapid eye movement sleep deprivation, and altered hormone levels.

Effects of rapid eye movement sleep deprivation on hypocretin neurons in the hypothalamus of a rat model of depression

Hypocretin (Hcrt, also known as orexin) is a hypothalamic neuropeptide linked to narcolepsy, a disorder diagnosed by the appearance of rapid eye-movement sleep (REMS)-state characteristics during waking. Major targets of Hcrt-containing fibers include the locus coeruleus and the raphe nucleus, areas with important roles in regulation of mood and sleep. A relationship between REMS and mood is suggested by studies demonstrating that REMS-deprivation (REMSD) ameliorates depressive symptoms in humans. Additional support is found in animal studies where antidepressants and REMSD have similar effects on monoamiergic systems thought to be involved in major depression. Recently, we have reported that Wistar-Kyoto (WKY) rats, an animal model of depression, have reduced number and size of hypothalamic cells expressing Hcrt-immunoractivity compared to the parent, Wistar (WIS) strain, suggesting the possibility that the depressive-like attributes of the WKY rat may be determined by this relative reduction in Hcrt cells [Allard, J.S., Tizabi, Y., Shaffery, J.P., Trouth, C.O., Manaye, K., 2004. Stereological analysis of the hypothalamic hypocretin/orexin neurons in an animal model of depression. Neuropeptides 38, 311-315]. In this study, we sought to test the hypothesis that REMSD would result in a greater increase in the number and/or size of hypothalamic, Hcrt-immunoreactive (Hcrt-ir) neurons in WKY, compared to WIS rats. The effect of REMSD, using the multiple-small-platforms-over-water (SPRD) method, on size and number of Hcrt-ir cells were compared within and across strains of rats that experienced multiple-large-platforms-over-water (LPC) as well as to those in a normal, home-cage-control (CC) setting. In accord with previous findings, the number of Hcrt-ir cells was larger in all three WIS groups compared to the respective WKY groups. REMSD produced a 20% increase (p<0.02) in the number of hypothalamic Hcrt-ir neurons in WKY rats compared to cage control WKY (WKY-CC) animals. However, an unexpected higher increase in number of Hcrt-ir cells was also observed in the WKY-LPC group compared to both WKY-CC (31%, p<0.001) and WKY-SPRD (20%, p<0.002) rats. A similar, smaller, but non-significant, pattern of change was noted in WIS-LPC group. Overall the data indicate a differential response to environmental manipulations where WKY rats appear to be more reactive than WIS rats. Moreover, the findings do not support direct antidepressant-like activity for REMSD on hypothalamic Hcrt neurons in WKY rats.

Pain-related behavior following REM sleep deprivation in the rat: Influence of peripheral nerve injury, spinal glutamatergic receptors and nitric oxide

We assessed whether pain-related behavior in neuropathic or control rats is changed following rapid eye movement sleep deprivation (REMSD). Furthermore, we determined the contribution of spinal glutamatergic receptors and nitric oxide to sensitivity changes following REMSD versus peripheral nerve injury. Pain behavior was assessed in Sprague–Dawley (SD) and Hannover–Wistar (HW) rats with a spinal nerve ligation or a sham operation. Nerve ligation produced mechanical hypersensitivity of the injured dermatome in all animals. Baseline sensitivity to mechanical stimulation was higher in the HW than the SD group, independent of nerve injury. In both strains, mechanical sensitivity of neuropathic and sham-operated animals was increased following 48 h of REMSD. Heat sensitivity of an uninjured dermatome was not different among experimental conditions. Reversal of mechanical hypersensitivity was attempted in HW rats by spinal administration of an antagonist of the metabotropic glutamate receptor 5 (mGluR 5) or the NMDA receptor and a nitric oxide synthase (NOS) inhibitor. Mechanical hypersensitivity induced by REMSD in unoperated rats was attenuated by all three drugs, while in neuropathic animals the mechanical anti-hypersensitive effect was most pronounced with the antagonist of the mGluR 5 or a NOS inhibitor. The results indicate that the strain of the animals markedly influences baseline withdrawal threshold to mechanical stimulation. Mechanical hypersensitivity following REMSD, however, is similarly increased in HW and SD strains, and the REMSD-associated increase in mechanical sensitivity is independent of nerve injury. Furthermore, mechanical hypersensitivities following REMSD and peripheral nerve injury share common spinal mechanisms involving, at least, the mGluR 5 and nitric oxide.

PS06.2 REM sleep deprivation induced increased brain excitability is mediated by modulation of Na-K ATPase activity in the rat brain

PS06.2 REM sleep deprivation induced increased brain excitability is mediated by modulation of Na-K ATPase activity in the rat brain

Rapid eye movement sleep deprivation selectively impairs recall of fear extinction in hippocampus-independent tasks in rats

Previous studies have shown that rapid eye movement (REM) sleep deprivation (RSD) exerts a detrimental effect on some memory tasks. However, whether post-learning RSD impairs memory for fear extinction, an important model of inhibitory learning, remains to be elucidated. The present study examined the effects of post-extinction RSD from 0 to 6 h and 6 to 12 h on recall of fear extinction tested 24 h after extinction training. We found that RSD from 0 to 6 h significantly increased freezing when recall of extinction of cued fear was tested in the context in which rats received extinction training whereas RSD from 6 to 12 h had no effect (experiments 1 and 2, two hippocampus-independent memory tasks). RSD at either time point had no effect on freezing when recall of extinction of cued fear was tested in the context different from that in which extinction training occurred (experiment 3, a hippocampus-dependent memory task). Additionally, we observed no effect of RSD at either time point on freezing during recall test for extinction of contextual fear (experiment 4, a hippocampus-dependent memory task). These results suggest that the effects of post-extinction RSD on memory for fear extinction are complex. RSD impairs recall of fear extinction in hippocampus-independent tasks, but does not affect recall of fear extinction in hippocampus-dependent tasks. Our findings extend previous research on the effects of RSD on learning and memory and support the notion that REM sleep is involved in memory process of certain tasks.

The Relationship Between REM Sleep and Memory Consolidation in Old Age and Effects of Cholinergic Medication

Recent findings in young adults suggest that rapid eye movement (REM) sleep plays a role in procedural memory consolidation. The significance of REM sleep for memory consolidation in old age has not yet been investigated. Effects of REM sleep manipulation on declarative and procedural memory consolidation were investigated in 107 healthy older adults, ages 60-82 years. Rapid eye movement sleep deprivation was achieved by REM sleep awakenings and compared with non-REM sleep awakenings. Rapid eye movement sleep augmentation was realized physiologically by REM sleep rebound and pharmacologically by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Memory performance was tested by a paired associate list and a mirror tracing task at 9:30 pm and 7:30 am with sleep intervening between 11:00 pm and 7:00 am. Although REM sleep deprivation led to a significant reduction in total and phasic REM sleep, memory consolidation remained unaffected. Both REM sleep augmentation groups showed a significant increase in phasic REM sleep, whereas only pharmacological cholinergic REM sleep manipulation exerted a significant positive effect on procedural memory consolidation. Because only after cholinergic stimulation of phasic REM sleep procedural memory consolidation is improved, cholinergic activation seems to be a crucial component of REM sleep-related memory consolidation in old age.