Strategies for Scientific and Practicall Search: is There Any Correlation Between the Development of the Gut-Brain Axis and the Sleep Characteristics in Infants?

The review provides the analysis of modern publications on the topic of correlation between development of intestinal microbiota and maturation of neurophysiological activity patterns (on the example of sleep age structure development). The importance of the stage maturation of intestinal microbiota in the concept of the gut-brain axis is presented. Mechanisms and mediators involved in this axis are described, and its ontogenetic significance is justified. The main stages of sleep function development in a child as an important component of the general mental health maturation in relation to environmental factors and family features are presented. Recommendations on sleep periods duration and estimation of sleep onset and sleep structure are also given. Direct and reverse correlations of quantitive and qualitative microbiota parameters with sleep efficiency are shown. Positive correlation was identified between sleep consolidation, number and diversity of Bacteroidetes species in intestinal microbiota, and composition of bacterial metabolites. The presence of such correlations is theoretical justification for further development of methods of pathogenetic therapy of both microbiota and sleep disorders.

Pedagogical Strategies for the Enhancement of Medical Education

Clearly, memory and learning are essential to medical education. To make memory and learning more robust and long-term, educators should turn to the advances in neuroscience and cognitive science to direct their efforts. This paper describes the memory pathways and stages with emphasis leading to long-term memory storage. Particular stress is placed on this storage as a construct known as schema. Leading from this background, several pedagogical strategies are described: cognitive load, dual encoding, spiral syllabus, bridging and chunking, sleep consolidation, and retrieval practice.

Homeostatic regulation of NREM sleep, but not REM sleep, in Australian magpies

Study Objectives We explore NREM and REM sleep homeostasis in Australian magpies (Cracticus tibicen tyrannica). We predicted that magpies would recover lost sleep by spending more time in NREM and REM sleep, and by engaging in more intense NREM sleep as indicated by increased slow-wave activity (SWA). Methods Continuous 72-h recordings of EEG, EMG and tri-axial accelerometry, along with EEG spectral analyses, were performed on wild-caught Australian magpies housed in indoor aviaries. Australian magpies were subjected to two protocols of night-time sleep deprivation: full 12-h night (n = 8) and first 6-h half of the night (n = 5), which were preceded by a 36-h baseline recording and followed by a 24-h recovery period. Results Australian magpies recovered lost NREM sleep by sleeping more, with increased NREM sleep consolidation, and increased SWA during recovery sleep. Following 12-h of night-time sleep loss, magpies also showed reduced SWA the following night after napping more during the recovery day. Surprisingly, the magpies did not recover any lost REM sleep. Conclusions Only NREM sleep is homeostatically regulated in Australian magpies with the level of SWA reflecting prior sleep/wake history. The significance of emerging patterns on the apparent absence of REM sleep homeostasis, now observed in multiple species, remains unclear.

Altered Sleep-Related Consolidation and Neurocognitive Comorbidity in CECTS

Our aim is to use neurophysiological sleep-related consolidation (SRC) phenomena to identify putative pathophysiological mechanisms in CECTS linked to diffuse neurocognitive deficits. We argue that there are numerous studies on the association between seizure aspects and neurocognitive functioning but not as many on interictal variables and neurocognitive deficits. We suggest two additional foci. First, the interictal presentation in CECTS and second, neuronal oscillations involved in SRC processes. Existing data on mechanisms through which interictal epileptiform spikes (IES) impact upon SRC indicate that they have the potential to: (a) perturb cross-regional coupling of neuronal oscillations, (b) mimic consolidation processes, (c) alter the precision of the spatiotemporal coupling of oscillations, and (d) variably impact upon SRC performance. Sleep spindles merit systematic study in CECTS in order to clarify: (a) the state of the slow oscillations (SOs) with which they coordinate, (b) the precision of slow oscillation-spindle coupling, and (c) whether their developmental trajectories differ from those of healthy children. We subsequently review studies on the associations between IES load during NREM sleep and SRC performance in childhood epilepsy. We then use sleep consolidation neurophysiological processes and their interplay with IES to help clarify the diffuse neurocognitive deficits that have been empirically documented in CECTS. We claim that studying SRC in CECTS will help to clarify pathophysiological mechanisms toward diverse neurocognitive deficits. Future developments could include close links between the fields of epilepsy and sleep, as well as new therapeutic neurostimulation targets. At the clinical level, children diagnosed with CECTS could benefit from close monitoring with respect to epilepsy, sleep and neurocognitive functions.

Astrocytic GABA Transporter controls sleep by modulating GABAergic signaling in Drosophila circadian neurons

A precise balance between sleep and wakefulness is essential to sustain a good quality of life and optimal brain function. GABA is known to play a key and conserved role in sleep control, and GABAergic tone should therefore be tightly controlled in sleep circuits. Here we examined the role of the astrocytic GABA transporter (GAT) in sleep regulation using Drosophila melanogaster. We found that a hypomorphic gat mutation (gat33-1) increased sleep amount, decreased sleep latency, and increased sleep consolidation. Interestingly, sleep defects were suppressed when gat33-1 was combined with a mutation disrupting wide-awake (wake), a gene that regulates the cell-surface levels of the GABAA receptor Resistance to Dieldrin (RDL) in the wake-promoting large ventral lateral neurons (l-LNvs). Moreover, RNAi knockdown of rdl and its modulator dnlg4 in these circadian neurons also suppressed gat33-1 sleep phenotypes. Brain immunohistochemistry showed that GAT-expressing astrocytes were located near RDL-positive l-LNvs cell bodies and dendritic processes. We conclude that astrocytic GAT decreases GABAergic tone and RDL activation in arousal promoting LNvs, thus determining proper sleep amount and quality in Drosophila

The molecular clockwork of the suprachiasmatic nucleus is sufficient to co-ordinate phasing and stabilisation of sleep-wake cycles and enhance memory deficits in a clockless mouse

The timing and quality of sleep-wake cycles are regulated by interacting circadian and homeostatic mechanisms. Although the suprachiasmatic nucleus (SCN) is the principal circadian clock, local clocks are active across the brain and the respective sleep-regulatory roles of SCN and extra-SCN clocks are unclear. To determine the specific contribution(s) of the SCN, we used virally mediated genetic complementation, expressing Cryptochrome1 (Cry1) to restore circadian molecular competence to the SCN of globally clockless Cry1/Cry2-null mice. Under free-running conditions, the rest/activity behaviour of Cry1/Cry2-null controls which received EGFP (SCNCon) was arrhythmic, whereas Cry1-complemented mice (SCNCry1) had circadian behaviour comparable to that of Cry1,2-competent wild-types (WT). In SCNCon mice, sleep-wakefulness, assessed by electroencephalography/electromyography, also lacked circadian organisation. In SCNCry1 mice, however, it was comparable to WT, with consolidated vigilance states (wake, REM and NREM sleep) and rhythms in NREMS delta power and expression of REMS within total sleep. Wakefulness in SCNCon mice was more fragmented than in WT, with more wake-NREMS-wake transitions. This disruption was corrected in SCNCry1 mice. Following sleep deprivation, all mice showed an initial homeostatic increase in NREMS delta power. The SCNCon mice, however, had reduced, non-consolidated NREMS during the inactive phase of the recovery period. In contrast, the dynamics of homeostatic responses in the SCNCry1 mice were equivalent to WT. Finally, SCNCon mice exhibited poor sleep-dependent memory but this was corrected in SCNCry1mice. Therefore, the SCN clock is sufficient for circadian control of sleep-wake, facilitating initiation and maintenance of wake, promoting sleep consolidation, homeostatic dynamics, and sleep-dependent memory.Significance statementThe circadian timing system regulates sleep-wake cycles. The hypothalamic suprachiasmatic nucleus (SCN) is the principal circadian clock, but local clocks are also active across the brain and the respective roles of SCN and local clocks in regulating sleep are unclear. To determine, explicitly, the contribution of the SCN, we used virally mediated genetic complementation to restore SCN molecular circadian functions in otherwise genetically clockless mice. This initiated circadian activity-rest cycles, accompanied by circadian sleep-wake cycles, circadian patterning to the intensity of NREM sleep and circadian control of REM sleep as a proportion of total sleep. Consolidation of sleep-wake established normal dynamics of sleep homeostasis and enhanced sleep-dependent memory. Thus, the SCN is the principal and sufficient circadian regulator of sleep-wake.

1066 Rapid Eye Movement (REM) Sleep Duration in Posttraumatic Stress Disorder (PTSD) Varies Dynamically and Directly Within the Individual With Indices of Sleep Consolidation and Parasympathetic Tone

Introduction Autonomic arousal in posttraumatic stress disorder (PTSD) has been associated with functional hypoactivation of the medial prefrontal cortex and hyperactivity of the amygdala which can directly affect sleep physiology including REM sleep. REM sleep has been associated with reduced fear conditioning; and PTSD has been associated with REM sleep fragmentation. A case report of a drug-free PTSD patient (Gupta MA,2019) who underwent 10 home sleep apnea tests (HSATs) observed a dynamic and inverse relation between REM sleep duration and indices of sympathetic activation during sleep and sleep fragmentation. This study has examined the relationship between REM sleep duration and sleep parameters related to sleep consolidation and parasympathetic tone in 17 PTSD patients who had completed at least 10 HSATs each. Methods 17 civilian PTSD patients (all female; mean±SD age: 47.59±10.52 years; 16 white) each completed 10 HSATs (WatchPAT200, Itamar)(over 1 to 45 months). The mean±SD initial PTSD Checklist for DSM-5 score was 49.24±13.08 (n=17), and Clinician Administered PTSD Scale for DSM-5 (CAPS-5) score was ≥55. Patients using benzodiazepines and/or narcotics were excluded. Results The overall mean±SD REM duration for all 10 visits (for 17x10 HSATs) was 84.40±8.65 minutes (range 69.13-96.97 min); the mean REM duration over the 10 HSATs correlated with other sleep indices as follows: sleep onset latency (Pearson r= -0.667, p=0.035); sleep efficiency (r=0.636, p=0.048); light sleep (NI+N2) percentage (r= -0.754, p=0.012); light sleep duration (r=0.692, p=0.027);deep sleep (N3) duration (r=0.635, p=0.048). Conclusion Over the 10 HSATs the average (n=17) REM sleep duration was directly related to indices of sleep consolidation (decreased sleep latency, increased sleep efficiency, increase in both light and deep sleep duration). The direct relation of REM sleep duration to duration of deep sleep, and inverse relation with light sleep percentage suggests REM sleep- related promotion of increased parasympathetic tone within the individual. Support None