Visuomotor adaptation modulates the clustering of sleep spindles into trains

Sleep spindles are thought to promote memory consolidation. Recently, we have shown that visuomotor adaptation (VMA) learning increases the density of spindles and promotes the coupling between spindles and slow oscillations, locally, with the level of spindle-SO synchrony predicting overnight memory retention. Yet, growing evidence suggests that the rhythmicity in spindle occurrence may also influence the stabilization of declarative and procedural memories. Here, we examined if VMA learning promotes the temporal organization of sleep spindles into trains. We found that VMA increased the proportion of spindles and spindle-SO couplings in trains. In agreement with our previous work, this modulation was observed over the contralateral hemisphere to the trained hand, and predicted overnight memory retention. Interestingly, spindles grouped in a cluster showed greater amplitude and duration than isolated spindles. The fact that these features increased as a function of train length, provides evidence supporting a biological advantage of this temporal arrangement. Our work opens the possibility that the periodicity of NREM oscillations may be relevant in the stabilization of procedural memories.

Opioids cause dissociated states of consciousness in C57BL/6J mice

The electroencephalogram (EEG) provides an objective, neural correlate of consciousness. Opioid receptors modulate mammalian neuronal excitability, and this fact was used to characterize how opioids administered to mice alter EEG power and states of consciousness. The present study tested the hypothesis that antinociceptive doses of fentanyl, morphine, or buprenorphine differentially alter the EEG and states of sleep and wakefulness in adult, male C57BL/6J mice. Mice were anesthetized and implanted with telemeters that enabled wireless recordings of cortical EEG and electromyogram (EMG). After surgical recovery, EEG and EMG were used to objectively score states of consciousness as wakefulness, rapid eye movement (REM) sleep, or non-REM (NREM) sleep. Measures of EEG power (dB) were quantified as delta (0.5 to 4 Hz), theta (4 to 8 Hz), alpha (8 to 13 Hz), sigma (12 to 15 Hz), beta (13 to 30 Hz), and gamma (30 to 60 Hz). Compared to saline (control), fentanyl and morphine decreased NREM sleep, morphine eliminated REM sleep, and buprenorphine eliminated NREM sleep and REM sleep. Opioids significantly and differentially disrupted the temporal organization of sleep/wake states, altered specific EEG frequency bands, and caused dissociated states of consciousness. The results are discussed relative to the fact that opioids, pain, and sleep modulate interacting states of consciousness.

The interindividual variability of sleep timing and circadian phase in humans is influenced by daytime and evening light conditions

Human cognitive functioning shows circadian variations throughout the day. However, individuals largely differ in their timing during the day of when they are more capable of performing specific tasks and when they prefer to sleep. These interindividual differences in preferred temporal organization of sleep and daytime activities define the chronotype. Since a late chronotype is associated with adverse mental and physical consequences, it is of vital importance to study how lighting environments affect chronotype. Here, we use a mathematical model of the human circadian pacemaker to understand how light in the built environment changes the chronotype distribution in the population. In line with experimental findings, we show that when individuals spend their days in relatively dim light conditions, this not only results in a later phase of their biological clock but also increases interindividual differences in circadian phase angle of entrainment and preferred sleep timing. Increasing daytime illuminance results in a more narrow distribution of sleep timing and circadian phase, and this effect is more pronounced for longer photoperiods. The model results demonstrate that modern lifestyle changes the chronotype distribution towards more eveningness and more extreme differences in eveningness. Such model-based predictions can be used to design guidelines for workplace lighting that help limiting circadian phase differences, and craft new lighting strategies that support human performance, health and wellbeing.

INFLUENCE OF MICRORNA MIR-101 ON THE STRUCTURAL AND FUNCTIONAL ORGANIZATION OF THE WAKE-SLEEP CYCLE UNDER AMYLOIDOSIS IN RATS

The effects of transnasal introduction of microRNA (miR-101) in liposomal form on the structural and functional organization of sleep were investigated under conditions of modeling Alzheimer's disease in rats of late adulthood. It is shown that in experimental amyloidosis, course administration of miR101 promotes a significant (22-fold) increase in the duration of the deep slow-wave phase and a two-fold increase in the production of paradoxical sleep that is accompanied by a normalization of the rhythmic organization of the wake-sleep cycle and reflects the positive direction of these effects on its qualitative characteristics, probably, due to the inhibitory effect on the synthesis of the precursor of β-amyloid peptides. The results obtained may indicate the prospects for further study of the therapeutic potential of miR-101.

REM sleep-dependent short-term and long-term hourglass processes in the ultradian organization and recovery of REM sleep in the rat

Study Objectives To evaluate the contribution of long-term and short-term REM sleep homeostatic processes to REM sleep recovery and the ultradian organization of the sleep wake cycle. Methods Fifteen rats were sleep recorded under a 12:12 LD cycle. Animals were subjected during the rest phase to two protocols (2T2I or 2R2I) performed separately in non-consecutive experimental days. 2T2I consisted of 2 h of total sleep deprivation (TSD) followed immediately by 2 h of intermittent REM sleep deprivation (IRD). 2R2I consisted of 2 h of selective REM sleep deprivation (RSD) followed by 2 h of IRD. IRD was composed of four cycles of 20-min RSD intervals alternating with 10 min of sleep permission windows. Results REM sleep debt that accumulated during deprivation (9.0 and 10.8 min for RSD and TSD, respectively) was fully compensated regardless of cumulated NREM sleep or wakefulness during deprivation. Protocol 2T2I exhibited a delayed REM sleep rebound with respect to 2R2I due to a reduction of REM sleep transitions related to enhanced NREM sleep delta-EEG activity, without affecting REM sleep consolidation. Within IRD permission windows there was a transient and duration-dependent diminution of REM sleep transitions. Conclusions REM sleep recovery in the rat seems to depend on a long-term hourglass process activated by REM sleep absence. Both REM sleep transition probability and REM sleep episode consolidation depend on the long-term REM sleep hourglass. REM sleep activates a short-term REM sleep refractory period that modulates the ultradian organization of sleep states.

Epilepsy in Tubulinopathy: Personal Series and Literature Review

Mutations in tubulin genes are responsible for a large spectrum of brain malformations secondary to abnormal neuronal migration, organization, differentiation and axon guidance and maintenance. Motor impairment, intellectual disability and epilepsy are the main clinical symptoms. In the present study 15 patients from a personal cohort and 75 from 21 published studies carrying mutations in TUBA1A, TUBB2B and TUBB3 tubulin genes were evaluated with the aim to define a clinical and electrophysiological associated pattern. Epilepsy shows a wide range of severity without a specific pattern. Mutations in TUBA1A (60%) and TUBB2B (74%) and TUBB3 (25%) genes are associated with epilepsy. The accurate analysis of the Electroencephalogram (EEG) pattern in wakefulness and sleep in our series allows us to detect significant abnormalities of the background activity in 100% of patients. The involvement of white matter and of the inter-hemispheric connection structures typically observed in tubulinopathies is evidenced by the high percentage of asynchronisms in the organization of sleep activity recorded. In addition to asymmetries of the background activity, excess of slowing, low amplitude and Magnetic Resonance (MR) imaging confirm the presence of extensive brain malformations involving subcortical and midline structures. In conclusion, epilepsy in tubulinopathies when present has a favorable evolution over time suggesting a not particularly aggressive therapeutic approach.

Neuronal substrates for initiation, maintenance, and structural organization of sleep/wake states

Animals continuously alternate between sleep and wake states throughout their life. The daily organization of sleep and wakefulness is orchestrated by circadian, homeostatic, and motivational processes. Over the last decades, much progress has been made toward determining the neuronal populations involved in sleep/wake regulation. Here, we will discuss how the application of advancedin vivotools for cell type–specific manipulations now permits the functional interrogation of different features of sleep/wake state regulation: initiation, maintenance, and structural organization. We will specifically focus on recent studies examining the roles of wake-promoting neuronal populations.