Dreaming of a learning task is associated with enhanced memory consolidation: Replication in an overnight sleep study

Sleep following learning benefits memory. One model attributes this effect to the iterative “reactivation” of memory traces in the sleeping brain, demonstrated in animal models. Although technical limitations prohibit using the same methods to observe memory reactivation in the human brain, the study of mental activity during sleep provides an alternative method of observing memory activation during sleep. In fact, the content of dream experience may reflect the process of memory reactivation and consolidation in the sleeping brain. In line with this hypothesis, we previously reported that dreaming about a spatial learning task during a nap strongly predicts subsequent performance improvements. Here, we replicate this observation in an overnight sleep study, for the first time demonstrating that pre‐sleep training on a virtual maze navigation task is reflected in dreams reported from all phases of sleep, with unambiguous representation of the task in dream content associated with improved next‐morning performance. These observations are consistent with reactivation‐based models of memory consolidation in sleep, confirming our earlier finding that the cognitive‐level activation of recent experience during sleep is associated with subsequent performance gains.     

Sleep‐dependent memory consolidation is related to perceived value of learned material

Although many types of newly encoded information can be consolidated during sleep, an enhanced effect has been found for memories tagged as relevant to the future, such as through knowledge of future testing or payment for successful recall. In the current study, participants (n = 80) learned Welsh and Breton translations of English words, and intrinsic relevance of learned material was operationalized as perceived value of the Welsh and Breton languages. Participants were non‐Welsh native English speakers who had recently arrived in Wales. Memory for the words was tested immediately and 12 h later, after either a period of wake or a period of sleep. An increase in recall for both languages was found after sleep, but not after wake. Importantly, for the sleep condition, overnight improvement in Welsh word recall was associated with participants’ level of valuing the Welsh language. This association was not found for the wake period condition. These findings support previous indications of an active role of sleep in the consolidation of memories relevant for the future, and demonstrate that this effect may be modulated by individual differences in perceived value of the learned material. It remains to be established whether this association is mediated by an emotional attachment to the language or a cognitive facility with it, or both.     

Rapid eye movement fragmentation,not slow‐wave sleep,predicts neutral declarative memory consolidation in posttraumatic stress disorder

Individuals diagnosed with posttraumatic stress disorder (PTSD) experience disruption at both slow‐wave sleep (SWS) and rapid‐eye movement (REM) sleep stages and demonstrate marked memory impairment. A small group of studies suggests that, within the disorder, there is a mechanistic relation between these sleep and memory impairments. This study sought to extend that literature by examining whether, in PTSD‐diagnosed individuals, memory‐retention deficits are present after a sleep‐filled (but not after a wake‐filled) delay (i.e., whether memory deficits can be traced to interruptions of sleep‐dependent memory consolidation). Moreover, we investigated whether SWS‐ or REM‐based disturbances, or both, contribute to retention deficits. We recruited participants into three groups: PTSD (n = 21), trauma‐exposed non‐PTSD (TE; n = 19) and healthy control (HC; n = 20). Using a crossover design, we assessed memory recall before and after an 8‐hr period of polysomnography‐monitored sleep and an 8‐hr period of regular waking activity. PTSD‐diagnosed participants retained less information than controls over the sleep‐filled (but not wake‐filled) delay. Furthermore, increased REM fragmentation predicted postsleep memory retention in PTSD‐diagnosed individuals only. No SWS parameter was associated with or predictive of the amount of information retained postsleep. We conclude that specific REM‐related changes in PTSD‐diagnosed individuals affected sleep‐dependent neutral declarative memory consolidation. Generally, these findings extend the literature suggesting that the co‐occurrence of sleep and memory difficulties in PTSD is not accidental, but that these two symptom clusters are meaningfully related. Specifically, the study illustrates that subtle REM‐related disruptions contribute most strongly to memory impairment in PTSD.     

Sleep/wake measurement using a non‐contact biomotion sensor

We studied a novel non‐contact biomotion sensor, which has been developed for identifying sleep/wake patterns in adult humans. The biomotion sensor uses ultra low‐power reflected radiofrequency waves to determine the movement of a subject during sleep. An automated classification algorithm has been developed to recognize sleep/wake states on a 30‐s epoch basis based on the measured movement signal. The sensor and software were evaluated against gold‐standard polysomnography on a database of 113 subjects [94 male, 19 female, age 53 ± 13 years, apnoea–hypopnea index (AHI) 22 ± 24] being assessed for sleep‐disordered breathing at a hospital‐based sleep laboratory. The overall per‐subject accuracy was 78%, with a Cohen’s kappa of 0.38. Lower accuracy was seen in a high AHI group (AHI >15, 63 subjects) than in a low AHI group (74.8% versus 81.3%); however, most of the change in accuracy can be explained by the lower sleep efficiency of the high AHI group. Averaged across subjects, the overall sleep sensitivity was 87.3% and the wake sensitivity was 50.1%. The automated algorithm slightly overestimated sleep efficiency (bias of +4.8%) and total sleep time (TST; bias of +19 min on an average TST of 288 min). We conclude that the non‐contact biomotion sensor can provide a valid means of measuring sleep–wake patterns in this patient population, and also allows direct visualization of respiratory movement signals.     

Sleep complaints are not corroborated by objective sleep measures in post-traumatic stress disorder: a 1-year prospective study in survivors of motor vehicle crashes

Disturbed sleep is a common complaint among patients with post-traumatic stress disorder (PTSD). However, laboratory studies of sleep in PTSD have provided inconsistent evidence of objective sleep disturbances. A major shortcoming of most previous studies is the fact that they were performed retrospectively in patients with chronic PTSD, often complicated by comorbid psychiatric disorders and drug abuse. Thus, little is known about the development of sleep disturbances in recently traumatized subjects. In this study, 102 motor vehicle collision (MVC) survivors were followed from the time of collision throughout 1 year. Nineteen subjects hospitalized for elective surgery served as a comparison group. Subjective quality of sleep was assessed using the mini-Sleep Questionnaire and the Sleep Habit Questionnaire. In addition, a 48-h actigraphic recording was obtained 1 week, 3 and 12 months after the collision. At 12 months, a structured clinical interview (SCID) was administered to reach a formal diagnosis of PTSD. Twenty-six of the MVC survivors, but none of the comparison subjects, met the diagnostic criteria for PTSD. While MVC survivors with PTSD reported markedly poorer sleep as reflected by significantly higher scores on the mini-Sleep Questionnaire, there were no significant differences between the three groups on the actigraphic measures that were largely normal. These results, which were obtained in subjects with no evidence of active psychiatric symptoms at the time of trauma and free of psychotropic or hypnotic medications, further support previous polysomnographic (PSG) studies suggesting that altered sleep perception, rather than sleep disturbance per se, may be the key problem in PTSD.     

Sleep condition and cognitive decline in Japanese community‐dwelling older people: Data from a 4‐year longitudinal study

This study examined whether sleep duration and excessive daytime sleepiness (EDS) are related to cognitive decline among community‐dwelling older adults with intact cognition at baseline, using 4‐year longitudinal data. A total of 3,151 community‐dwelling older individuals aged ≥65 years were studied. They were assessed for cognitive function, including memory, attention, executive function and processing speed. Cognitive impairment was defined based on a score >1.5 standard deviations below the age‐ and education‐specific mean. Cognitive decline was defined in one or more cognitive tests at follow‐up. Self‐reported sleep duration (short, ≤6.0 hr; medium, 6.1–8.9 hr; long, ≥9.0 hr) and EDS at first‐wave examination were assessed and logistic regression analyses were used to examine the associations of sleep duration and EDS with cognitive status at second‐wave examination. The incidence of cognitive decline differed significantly among the sleep‐duration groups (short, 15.9%; medium, 11.9%; long, 20.1%; p = 0.001). The prevalence of having EDS was 13.1%, which was associated with a higher rate of cognitive decline than having no EDS (18.9% vs. 12.5%, p = 0.004). Long sleep duration compared with medium sleep duration (OR, 1.50; 95% CI, 1.05–2.13) and EDS (1.43; 1.01–2.03) independently impacted the incidence of cognitive decline. The results were similar after multiple imputations (long, 1.68, 1.12–2.52; EDS, 1.55, 1.05–2.29). In conclusion, our study revealed that both long sleep duration and EDS were independent risk factors associated with cognitive decline after 4 years among older adults.     

Energy Expenditure is Affected by Rate of Accumulation of Sleep Deficit in Rats

Study Objectives:

Short sleep is a putative risk factor for obesity. However, prolonged total sleep deprivation (TSD) leads to negative energy balance and weight loss in rodents, whereas sleep-restricted humans tend to gain weight. We hypothesized that energy expenditure (V̇O₂) is influenced by the rate of accumulation of sleep deficit in rats.

Design and Intervention:

Six Sprague-Dawley rats underwent chronic sleep-restriction (CSR, 6-h sleep opportunity at ZT0-6 for 10 days) and stimulus-control protocols (CON, 12-h sleep opportunity for 10 days, matched number of stimuli) in a balanced cross-over design. Four additional rats underwent TSD (4 days). Sleep was manipulated using a motor-driven walking wheel.

Measurements and Results:

Electroencephalography, electromyography, and body temperature were measured by telemetry, and V̇O₂, by respirometry. Total sleep deficits of 55.1 ± 6.4 hours, 31.8 ± 6.8 hours, and 38.2 ± 2.3 hours accumulated over the CSR, CON, and TSD protocols, respectively. Responses to TSD confirmed previous reports of elevated V̇O₂ and body temperature. These responses were attenuated in CSR, despite a greater cumulative sleep deficit. Rate of rise of O₂ was strongly correlated with rate of accumulation of sleep deficit, above a threshold deficit of 3.6 h·day⁻¹.

Conclusion:

The change in V̇O₂ is affected by rate of accumulation of sleep deficit and not the total sleep loss accrued. Negative energy balance, observed during TSD, is strongly attenuated when brief daily sleep opportunities are available to rats (CSR), despite greater accumulated sleep deficit.

Citation:

Caron AM; Stephenson R. Energy expenditure is affected by rate of accumulation of sleep deficit in rats. SLEEP 2010;33(9):1226-1235.     

Sleep and memory consolidation: The role of electrophysiological neuroimaging

Summary Memory consolidation involves a complex series of molecular, cellular and network-level processes that take place on time scales from millisecond to months. Evidence from a wide range of experimental observations supports the hypothesis that parts of these processes occur during sleep when the brain is not engaged in processing and encoding incoming information. Indeed, sleep seems to be favorable for brain plasticity. Experience-dependent cortical plasticity observed during sleep has been hypothesized to be part of the global process of memory consolidation. Thus, studying task-dependent, regionally specific reactivation of neuronal assemblies during posttraining sleep may make important contributions to elucidating the role of sleep in memory trace processing. A new methodology – low-resolution brain electromagnetic tomography (LORETA) – offers the possibility of localizing electrical activity produced by cortical neuronal generators under normal (undisturbed) sleeping conditions. The high time resolution of brain electrical data can be exploited to produce neuroimages for specific EEG spectral frequency bands (e.g. delta, theta, or spindle bands). This makes it possible to investigate, dependent on the type of memory, when – in which sleep stages (S2 sleep, SWS, REM sleep) – and where – in which cortical brain regions (primary sensory cortex, higher association cortex) – experience-dependent reactivation occurs.     

Sleep‐disordered breathing in children is associated with impairment of sleep stage‐specific shift of cardiac autonomic modulation

We examined the effects of sleep stages and sleep‐disordered breathing (SDB) on autonomic modulation in 700 children. Apnea hypopnea index (AHI) during one 9 h night‐time polysomnography was used to define SDB. Sleep stage‐specific autonomic modulation was measured by heart rate variability (HRV) analysis of the first available 5 min RR intervals from each sleep stage. The mean [standard deviation (SD)] age was 112 (21) months (49% male and 25% non‐Caucasian). The average AHI was 0.79 (SD = 1.03) h^?1, while 73.0%, 25.8% and 1.2% of children had AHI <1 (no SDB), 1–5 (mild SDB) and ≥5 (moderate SDB), respectively. In the no SDB group, the high frequency (HF) and root mean square SD (RMSSD) increased significantly from wake to Stage 2 and slow wave sleep (SWS), and then decreased dramatically when shifting into rapid eye movement (REM) sleep. In the moderate SDB group, the pattern of HRV shift was similar to that of no SDB. However, the decreases in HF and RMSSD from SWS to REM were more pronounced in moderate SDB children [between‐group differences in HF (?24% in moderate SDB versus ?10% in no SDB) and RMSSD (?27% versus ?12%) were significant (P < 0.05)]. The REM stage HF is significantly lower in the moderate SDB group compared to the no SDB group [mean (standard error): 4.49 (0.43) versus 5.80 (0.05) ms², respectively, P < 0.05]. Conclusions are that autonomic modulation shifts significantly towards higher parasympathetic modulation from wake to non‐rapid eye movement sleep, and reverses to a less parasympathetic modulation during REM sleep. However, the autonomic modulation is impaired among children with moderate SDB in the directions of more reduction in parasympathetic modulation from SWS to REM sleep and significantly weaker parasympathetic modulation in REM sleep, which may lead to higher arrhythmia vulnerability, especially during REM sleep.     

Analgesia induced by self‐initiated electrotactile sensation is mediated by top‐down modulations

It is well known that sensory perception can be attenuated when sensory stimuli are controlled by self‐initiated actions. This phenomenon is explained by the consistency between forward models of anticipated action effects and actual sensory feedback. Specifically, the brain state related to the binding between motor processing and sensory perception would have inhibitory function by gating sensory information via top‐down control. Since the brain state could casually influence the perception of subsequent stimuli of different sensory modalities, we hypothesize that pain evoked by nociceptive stimuli following the self‐initiated tactile stimulation would be attenuated as compared to that following externally determined tactile stimulation. Here, we compared psychophysical and neurophysiological responses to identical nociceptive‐specific laser stimuli in two different conditions: self‐initiated tactile sensation condition (STS) and nonself‐initiated tactile sensation condition (N‐STS). We observed that pain intensity and unpleasantness, as well as laser‐evoked brain responses, were significantly reduced in the STS condition compared to the N‐STS condition. In addition, magnitudes of alpha and beta oscillations prior to laser onset were significantly larger in the STS condition than in the N‐STS condition. These results confirmed that pain perception and pain‐related brain responses were attenuated when the tactile stimulation was initiated by subjects’ voluntary actions, and exploited neural oscillations reflecting the binding between motor processing and sensory feedback. Thus, our study elaborated the understanding of underlying neural mechanisms related to top‐down modulations of the analgesic effect induced by self‐initiated tactile sensation, which provided theoretical basis to improve the analgesic effect in various clinical applications.     

EEG sigma and slow‐wave activity during NREM sleep correlate with overnight declarative and procedural memory consolidation

Previous studies suggest that sleep‐specific brain activity patterns such as sleep spindles and electroencephalographic slow‐wave activity contribute to the consolidation of novel memories. The generation of both sleep spindles and slow‐wave activity relies on synchronized oscillations in a thalamo‐cortical network that might be implicated in synaptic strengthening (spindles) and downscaling (slow‐wave activity) during sleep. This study further examined the association between electroencephalographic power during non‐rapid eye movement sleep in the spindle (sigma, 12–16 Hz) and slow‐wave frequency range (0.1–3.5 Hz) and overnight memory consolidation in 20 healthy subjects (10 men, 27.1 ± 4.6 years). We found that both electroencephalographic sigma power and slow‐wave activity were positively correlated with the pre–post‐sleep consolidation of declarative (word list) and procedural (mirror‐tracing) memories. These results, although only correlative in nature, are consistent with the view that processes of synaptic strengthening (sleep spindles) and synaptic downscaling (slow‐wave activity) might act in concert to promote synaptic plasticity and the consolidation of both declarative and procedural memories during sleep.     

Sleep architecture as correlate and predictor of symptoms and impairment in inter‐episode bipolar disorder: taking on the challenge of medication effects

This study was designed to clarify the association between inter‐episode bipolar disorder (BD) and sleep architecture. Participants completed a baseline symptom and sleep assessment and, 3 months later, an assessment of symptoms and impairment. The effects of psychiatric medications on sleep architecture were also considered. Participants included 22 adults with BD I or II (inter‐episode) and 22 non‐psychiatric controls. The sleep assessment was conducted at the Sleep and Psychological Disorders Laboratory at the University of California, Berkeley. Follow‐up assessments 3 months later were conducted over the phone. Results indicate that, at the sleep assessment, BD participants exhibited greater rapid eye movement sleep (REM) density than control participants with no other group differences in sleep architecture. Sleep architecture was not correlated with concurrent mood symptoms in either group. In the BD group, duration of the first REM period and slow‐wave sleep (SWS) amount were positively correlated with manic symptoms and impairment at 3 months, while REM density was positively correlated with depressive symptoms and impairment at 3 months. The amount of Stage 2 sleep was negatively correlated with manic symptoms and impairment at 3 months. In contrast, for the control group, REM density was negatively correlated with impairment at 3 months. SWS and Stage 2 sleep were not correlated with symptoms or impairment. Study findings suggest that inter‐episode REM sleep, SWS and Stage 2 sleep are correlated with future manic and depressive symptoms and impairment in BD. This is consistent with the proposition that sleep architecture may be a mechanism of illness maintenance in BD.     

The effect of sleep‐specific brain activity versus reduced stimulus interference on declarative memory consolidation

Studies suggest that the consolidation of newly acquired memories and underlying long‐term synaptic plasticity might represent a major function of sleep. In a combined repeated‐measures and parallel‐group sleep laboratory study (active waking versus sleep, passive waking versus sleep), we provide evidence that brief periods of daytime sleep (42.1 ± 8.9 min of non‐rapid eye movement sleep) in healthy adolescents (16 years old, all female), compared with equal periods of waking, promote the consolidation of declarative memory (word‐pairs) in participants with high power in the electroencephalographic sleep spindle (sigma) frequency range. This observation supports the notion that sleep‐specific brain activity when reaching a critical dose, beyond a mere reduction of interference, promotes synaptic plasticity in a hippocampal‐neocortical network that underlies the consolidation of declarative memory.     

Sleep and sleepiness among first‐time postpartum parents: A field‐ and laboratory‐based multimethod assessment

The study aim was to compare sleep, sleepiness, fatigue, and neurobehavioral performance among first‐time mothers and fathers during their early postpartum period. Participants were 21 first‐time postpartum mother–father dyads (N = 42) and seven childless control dyads (N = 14). Within their natural environment, participants completed 1 week of wrist actigraphy monitoring, along with multi‐day self‐administered sleepiness, fatigue, and neurobehavioral performance measures. The assessment week was followed by an objective laboratory‐based test of sleepiness. Mothers obtained more sleep compared to fathers, but mothers' sleep was more disturbed by awakenings. Fathers had greater objectively measured sleepiness than mothers. Mothers and fathers did not differ on subjectively measured sleep quality, sleepiness, or fatigue; however, mothers had worse neurobehavioral performance than fathers. Compared to control dyads, postpartum parents experienced greater sleep disturbance, sleepiness, and sleepiness‐associated impairments. Study results can inform social policy, postpartum sleep intervention development, and research on postpartum family systems and mechanisms that propagate sleepiness. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 361–372, 2013     

Sleep continuity and total sleep time are associated with task‐switching and preparation in young and older adults

Ageing is associated with changes in sleep and decline executive functions, such as task‐switching and task preparation. Given that sleep affects executive function, age‐related changes in executive function may be attributable to changes in sleep. The present study used a sleep detection device to examine whether or not wake time after sleep onset and total sleep time moderated age differences in task‐switching performance and participants' ability to reduce switch costs when given time to prepare. Participants were cognitively healthy [Mini Mental State Examination > 26] younger (n = 54; mean age = 22.9; 67.8% female) and older (n = 45; mean age 62.8; 71.1% female) adults. Using a task‐switching paradigm, which manipulated preparation time, we found that smaller global switch costs were associated with lower wake time after sleep onset and longer total sleep time. Greater preparation effects on local switch costs and adoption of a task‐set were associated with lower wake time after sleep onset, although this effect was significant only in older adults when stratified by age group. This association was independent of inhibition and working memory abilities. The lack of interactions between sleep and age group indicated that age differences in switch costs were not moderated by better sleep. Our results suggest that young and older adults may benefit similarly from lower wake time after sleep onset and longer total sleep time in overall performance, and individuals with less wake time after sleep onset are more likely to engage preparatory strategies to reduce switch costs and boost task‐switching performance.     

A reconceptualization of EEG alpha activity as an index of arousal during sleep: all alpha activity is not equal

SUMMARY  Alpha activity occurring during sleep is generally considered to reflect arousal processes and a shift toward wakefulness. This long-standing interpretation is based on physiological and behavioural arousal correlates of alpha activity presumed to have an occipital focus. In addition to the application of this interpretation to sleep/wake state determinations, there have been reports of nonrefreshing or nonrestorative sleep in clinical populations exhibiting dramatic amounts of alpha intrusion during sleep in the absence of awakening. Reports of the presence of alpha activity during sleep in normal subjects without sleep disruption or complaints of daytime sleepiness call into question the interpretation that this activity is associated with arousal. A re-examination of this literature, incorporating the results from recent investigations employing multi-site EEG recordings, electronic processing and source diple analyses of this activity, suggests the existence of alpha activity which differs in generation site (thalamus), scalp distribution (frontal-central), and behavioural correlates (e.g. enhancement to stimulation during wakefulness, concentration in the first-half of the night during sleep, and absence of sleep disturbance) from occipital alpha activity. Such marked differences in defining characteristics imply different functional correlates for these activities. In this context, it is proposed that this fronto-central alpha activity is associated with sleep-maintaining processes which may be enhanced in response to sleep-disturbing events.     

The wrist is not the brain: Estimation of sleep by clinical and consumer wearable actigraphy devices is impacted by multiple patient‐ and device‐specific factors

Clinical actigraphy devices provide adequate estimates of some sleep measures across large groups. In practice, providers are asked to apply clinical or consumer wearable data to individual patient assessments. Inter‐individual variability in device performance will impact such patient‐specific interpretation. We assessed two devices, clinical and consumer, to determine the magnitude and predictors of this individual‐level variability. One hundred and two patients (55 [53.9%] female; 56.4 [±16.3] years old) undergoing polysomnography wore Jawbone UP3 and/or Actiwatch2. Device total sleep time, sleep efficiency, wake after sleep onset and sleep latency were compared with polysomnography. Demographics, sleep architecture and clinical measures were compared to device performance. Actiwatch overestimated total sleep time by 27.2 min (95% confidence limits [CL], 138.3 min over to 84.0 under), overestimated sleep efficiency by 6.8% (95% CL, 34.1% over to 20.5% under), overestimated sleep onset latency by 2.6 min (95% CL, 63.3 over to 58.2 under) and underestimated wake after sleep onset by 50.7 min (95% CL, 162.5 under to 61.2 over). Jawbone overestimated total sleep time by 59.1 min (95% CL, 208.6 min over to 90.5 under) and overestimated sleep efficiency by 14.9% (95% CL, 52.6% over to 22.7% under). In multivariate models, age, sleep onset latency, wake after sleep onset, % N1 and apnea–hypopnea index explained only some of the variance in device performance. Gender also affected performance. Actiwatch and Jawbone mis‐estimate sleep measures with very wide confidence limits and accuracy varies with multiple patient‐level characteristics. Given these large individual inaccuracies, data from these devices must be applied only with extreme caution in clinical practice.     

Objective but not subjective sleep predicts memory in community‐dwelling older adults

Research on the relationship between habitual sleep patterns and memory performance in older adults is limited. No previous study has used objective and subjective memory measures in a large, older‐aged sample to examine the association between sleep and various domains of memory. The aim of this study was to examine the association between objective and subjective measures of sleep with memory performance in older adults, controlling for the effects of potential confounds. One‐hundred and seventy‐three community‐dwelling older adults aged 65–89 years in Victoria, Australia completed the study. Objective sleep quality and length were ascertained using the Actiwatch 2 Mini‐Mitter, while subjective sleep was measured using the Pittsburgh Sleep Quality Index. Memory was indexed by tests of retrospective memory (Hopkins Verbal Learning Test – Revised), working memory (n‐back, 2‐back accuracy) and prospective memory (a habitual button pressing task). Compared with normative data, overall performance on retrospective memory function was within the average range. Hierarchical regression was used to determine whether objective or subjective measures of sleep predicted memory performances after controlling for demographics, health and mood. After controlling for confounds, actigraphic sleep indices (greater wake after sleep onset, longer sleep‐onset latency and longer total sleep time) predicted poorer retrospective (?R² = 0.05, P = 0.016) and working memory (?R² = 0.05, P = 0.047). In contrast, subjective sleep indices did not significantly predict memory performances. In community‐based older adults, objectively‐measured, habitual sleep indices predict poorer memory performances. It will be important to follow the sample longitudinally to determine trajectories of change over time.     

Influence of three-day morphine-treatment upon impairment of memory consolidation induced by cannabinoid infused into the dorsal hippocampus in rats

In the present study, the effects of morphine treatment upon reduction of memory consolidation by post-training administration of the non-selective cannabinoid CB(1)/CB(2) receptor agonist, WIN55,212-2, into the dorsal hippocampus (intra-CA1) have been investigated in rats. Step-through inhibitory avoidance apparatus was used to test memory retrieval, which was made of two white and dark compartments. In training day, electric shocks were delivered to the grid floor of the dark compartment. On the test day, the animal was placed in the white compartment and allowed to enter the dark compartment. The latency with which the animal crossed into the dark compartment was recorded as memory retrieval. Morphine was injected subcutaneously (S.C.), once daily for three days, followed by a five day morphine-free period before training. Bilateral post-training intra-CA1 infusions of WIN55,212-2 (0.25 and 0.5 μg/rat) shortened the step-through latency, which suggested impaired memory consolidation. The deleterious effect of WIN55,212-2 (0.5 μg/rat) was prevented in rats previously injected with morphine (10 mg/kg/day × 3 days, S.C.). Prevention of the WIN55,212-2-induced amnesic-like effect was counteracted by the mu-receptor antagonist, naloxone, and the dopamine D(2) receptor antagonist, sulpiride, but not by the D(1) receptor antagonist, SCH 23390, when administered prior to each morphine injection. The results have suggested that subchronic morphine treatment may cause mu-opioid and D(2) receptor sensitization, which in turn prevents impairment of memory consolidation induced by WIN55,212-2.     

Interconnectivity of sympathetic and sleep networks is mediated through reduction of gamma aminobutyric acidergic inhibition in the paraventricular nucleus

Chronic short sleep duration has been linked to sympathoexcitation and increased risk of cardiovascular disease. The central nervous system plays an important role in the regulation of sympathetic activity. Thus, the present study evaluates the pre‐autonomic neurones in the paraventricular nucleus of the hypothalamus and rostral ventrolateral medulla after sleep restriction using various protein expression measurements and electrophysiological approaches. Wistar male rats were assigned randomly to two experimental groups: control or sleep restriction for 14 days. Sleep restriction was defined as 20 h of paradoxical sleep deprivation followed by a 4 h sleep permission period using the modified multiple platform method. Micropunches of the paraventricular nucleus of the hypothalamus and rostral ventrolateral medulla were dissected to evaluate the protein expression of angiotensin II receptor, type 1 (AT1), AT2, gamma aminobutyric acid_A) (N‐methyl‐d ‐aspartate receptor1) and neuronal nitric oxide synthase neuronal nitric oxide synthase isoform through immunoblotting. Sleep restriction induced a down‐regulation of the gamma aminobutyric acid_A receptor in the paraventricular nucleus of the hypothalamus. Microinjection of bicuculline, a gamma aminobutyric acid receptor blocker, into the paraventricular nucleus of the hypothalamus increased renal sympathetic activity renal sympathetic nerve activity, mean arterial pressure and heart rate in anaesthetized control rats. However, the amplitude and frequency of renal sympathetic nerve activity was higher in the sleep restriction group. These findings suggest that gamma aminobutyric acidergic inhibition within the paraventricular nucleus of the hypothalamus is involved in sympathoexcitation induced by sleep restriction.