Quercetin Modulates Behavioural and Biochemical Alterations in Stressed Mice

Disruption of the active phase of sleep alters the physiological homeostasis of the body and results in oxidative breakdown which may trigger a wide array of defects. The central nervous system and the metabolic system are some of the most affected systems as described in several literatures. Some plant based compounds with antioxidant property have been previously described in the abrogation of the deleterious effects of active sleep disruption. One of such compounds is quercetin. This study was premeditated to expatiate on the probable neuroprotective effect of quercetin on mice exposed to 72hr active sleep disruption. Mice were allotted into five treatment groups (n = 6): group 1 served as control, group 2 received 10 mL/kg vehicle, groups 3 and 4 received 25 and 50 mg/kg quercetin respectively, and group 5 received 50 mg/kg astaxanthin. Treatment lasted for 7 days while groups 2-5 were exposed to the sleep deprivation protocol starting from day 4. Behavioural tests followed by biochemical assays and histopathological changes in the prefrontal cortex were evaluated. Data were analysed by ANOVA set at p<0.05 significance. The results revealed that quercetin, in both doses, significantly amplified memory performance, attenuated depression-like behaviour, replenished catalase and superoxide dismutase, attenuated nitric oxide levels in brain and liver of mice when compared to control group and protected against loss of prefrontal cortex neurons. In conclusion, quercetin possesses protective effects against sleep deprivation-induced brain damage.

Balancing Prediction and Surprise: A Role for Active Sleep at the Dawn of Consciousness?

The brain is a prediction machine. Yet the world is never entirely predictable, for any animal. Unexpected events are surprising, and this typically evokes prediction error signatures in mammalian brains. In humans such mismatched expectations are often associated with an emotional response as well, and emotional dysregulation can lead to cognitive disorders such as depression or schizophrenia. Emotional responses are understood to be important for memory consolidation, suggesting that positive or negative ‘valence’ cues more generally constitute an ancient mechanism designed to potently refine and generalize internal models of the world and thereby minimize prediction errors. On the other hand, abolishing error detection and surprise entirely (as could happen by generalization or habituation) is probably maladaptive, as this might undermine the very mechanism that brains use to become better prediction machines. This paradoxical view of brain function as an ongoing balance between prediction and surprise suggests a compelling approach to study and understand the evolution of consciousness in animals. In particular, this view may provide insight into the function and evolution of ‘active’ sleep. Here, we propose that active sleep – when animals are behaviorally asleep but their brain seems awake – is widespread beyond mammals and birds, and may have evolved as a mechanism for optimizing predictive processing in motile creatures confronted with constantly changing environments. To explore our hypothesis, we progress from humans to invertebrates, investigating how a potential role for rapid eye movement (REM) sleep in emotional regulation in humans could be re-examined as a conserved sleep function that co-evolved alongside selective attention to maintain an adaptive balance between prediction and surprise. This view of active sleep has some interesting implications for the evolution of subjective awareness and consciousness in animals.

Developmental onset of a cerebellar-dependent forward model of movement in motor thalamus

To execute complex behavior with temporal precision, adult animals use internal models to predict the sensory consequences of self-generated movement. Here, taking advantage of the unique kinematic features of twitches-the brief, discrete movements of active sleep-we captured the developmental onset of a cerebellar-dependent internal model. Using rats at postnatal days (P) 12, P16, and P20, we compared neural activity in two thalamic structures: the ventral posterior (VP) and ventral lateral (VL) nuclei, both of which receive somatosensory input but only the latter of which receives cerebellar input. At all ages, twitch-related activity in VP lagged behind movement, consistent with sensory processing; similar activity was observed in VL through P16. At P20, however, VL activity precisely mimicked the twitch itself, a pattern of activity that depended on cerebellar input. Altogether, these findings implicate twitches in the development and refinement of internal models of movement.

Sensory coding of limb kinematics in developing primary motor cortex

Primary motor cortex (M1) undergoes protracted development in rodents, functioning initially as a sensory structure. As we reported previously in neonatal rats (Dooley and Blumberg, 2018), self-generated forelimb movements—especially the twitch movements that occur during active sleep—trigger sensory feedback (reafference) that strongly activates M1. Here, we expand our investigation by using a video-based approach to quantify the kinematic features of forelimb movements with sufficient precision to reveal receptive-field properties of individual M1 units. At postnatal day (P) 8, nearly all M1 units were strongly modulated by movement amplitude, but only during active sleep. By P12, the majority of M1 units no longer exhibited amplitude-dependence, regardless of sleepwake state. At both ages, movement direction produced changes in M1 activity, but to a much lesser extent than did movement amplitude. Finally, we observed that population spiking activity in M1 becomes more continuous and decorrelated between P8 and P12. Altogether, these findings reveal that M1 undergoes a sudden transition in its receptive field properties and population-level activity during the second postnatal week. This transition marks the onset of the next stage in M1 development before the emergence of its later-emerging capacity to influence motor outflow.

Sleep–wake regulation in preterm and term infants

Study Objectives In adults, wakefulness can be markedly prolonged at the expense of sleep, e.g. to stay vigilant in the presence of a stressor. These extra-long wake bouts result in a heavy-tailed distribution (highly right-skewed) of wake but not sleep durations. In infants, the relative importance of wakefulness and sleep are reversed, as sleep is necessary for brain maturation. Here, we tested whether these developmental pressures are associated with the unique regulation of sleep–wake states. Methods In 175 infants of 28–40 weeks postmenstrual age (PMA), we monitored sleep–wake states using electroencephalography and behavior. We constructed survival models of sleep–wake bout durations and the effect of PMA and other factors, including stress (salivary cortisol), and examined whether sleep is resilient to nociceptive perturbations (a clinically necessary heel lance). Results Wake durations followed a heavy-tailed distribution as in adults and lengthened with PMA and stress. However, differently from adults, active sleep durations also had a heavy-tailed distribution, and with PMA, these shortened and became vulnerable to nociception-associated awakenings. Conclusions Sleep bouts are differently regulated in infants, with especially long active sleep durations that could consolidate this state’s maturational functions. Curtailment of sleep by stress and nociception may be disadvantageous, especially for preterm infants given the limited value of wakefulness at this age. This could be addressed by environmental interventions in the future.

0067 An Anatomic Substrate for GABAergic Processes to Suppress Active Sleep and Promote Wakefulness in the Nucleus Pontis Oralis

Introduction Our previous electrophysiologic data have provided compelling evidence that GABAergic processes in the nucleus pontis oralis (NPO) play a critical role in the generation and maintenance of wakefulness as well as active (REM) sleep (AS). We therefore hypothesized that one of the neuronal mechanisms of GABA actions in the NPO to promote wakefulness and suppress AS is due to a direct GABAergic inhibition of NPO neurons that generate AS (AS-generator neurons). However, the anatomical substrate for this inhibition is undetermined. Accordingly, the present study was undertaken to examine whether there is any direct interaction between GABAergic neurons and glutamatergic AS-generator neurons in the NPO. Methods Adult cats were deeply anesthetized and perfused transcardially. The brainstem containing the NPO was removed, postfixed and cut into 15 μm coronal sections with a Reichert-Jung cryostat. The sections were incubated with a mixture of a rabbit polyclonal antibodies against glutamine and GABA following the procedure of double fluorescence immunohistochemistry. Results There was a large number of neuronal somata labeled by anti-glutamine antibody and terminals labeled by anti-GABA antibody in the NPO. These glutamine-positive neurons were medium to large, multipolar cells (&gt; 20 μm), which resemble glutamatergic, AS-generator neurons that have been previously identified in the NPO. Specifically, majority of glutamatergic neuronal somata were closely apposed by multiple GABAergic terminals, indicating that AS-generator neurons in the NPO receive direct GABAergic inputs. Conclusion The present results demonstrate that a direct connection exists between glutamatergic AS-generator neurons and GABAergic processes in the NPO. These data provide the anatomical evidence which supports our hypothesis that the pontine GABAergic control of wakefulness and active sleep is partially mediated via GABAergic processes project to NPO AS-generator neurons that suppress the activity of these cells. Support NS092383

The feature of brain oxygenation in the sleep cycle of healthy newborn babies

Noninvasive monitoring brain oxygenation with near-infrared spectroscopy (NIRS) is becoming a widely used in neonatology for determine the optimal target oxygen saturation during resuscitation of newborns, but its use in clinical practice for diagnostics and prognosis perinatal pathology is limited because intra and especially interpatient variability are too large for this aim. This study aimed to determine cerebral oximetry values during the sleep cycle and wakefulness in healthy full term newborns. 38 newborns (gestational age 38 weeks were included in this study (22 after normal birth I group and 16 after cesarean section). Near-infrared spectroscopy (CrSO2) from left fronto-parietal region was recorded in synchrony with polysomnography. Continuous cerebral CrSO2 were measured using near-infrared spectroscopy (Somanetic INVOS 5100C, USA). Fraction tissue oxygen extraction (FTOE) was calculated using SaO2 (pulse oximeter Radical Masimo) and CrSO2 (FTOE = (SаO2 CrSO2)/SаO2). CrSO2 and SаO2 were analyzed during 15 minutes polysomnography-defined quiet, active sleep and wakefulness (defined according to standard guidelines). The results: cerebral oxygen saturation varies with sleep-wake states: during active sleep (74,18 0,75%) was similar to the value in wakefulness (75,6 1,0%) and smaller than in quiet sleep (81,93 1,74%, р 0,001), but FTOE during active sleep was significantly higher (0,221 0,008% and 0,129 0,005%, p 0,001). There were no differences of rates between groups. The high oxygen consumption during REM sleep supports its role during postnatal brain functional development. The use of NIRS taking into account sleep structure will be new method for diagnostic and prognosis perinatal pathology CNS.

Active Sleep Promotes Coherent Oscillatory Activity in the Cortico-Hippocampal System of Infant Rats

Active sleep (AS) provides a unique developmental context for synchronizing neural activity within and between cortical and subcortical structures. In week-old rats, sensory feedback from myoclonic twitches, the phasic motor activity that characterizes AS, promotes coherent theta oscillations (4–8 Hz) in the hippocampus and red nucleus, a midbrain motor structure. Sensory feedback from twitches also triggers rhythmic activity in sensorimotor cortex in the form of spindle bursts, which are brief oscillatory events composed of rhythmic components in the theta, alpha/beta (8–20 Hz), and beta2 (20–30 Hz) bands. Here we ask whether one or more of these spindle-burst components are communicated from sensorimotor cortex to hippocampus. By recording simultaneously from whisker barrel cortex and dorsal hippocampus in 8-day-old rats, we show that AS, but not other behavioral states, promotes cortico-hippocampal coherence specifically in the beta2 band. By cutting the infraorbital nerve to prevent the conveyance of sensory feedback from whisker twitches, cortical-hippocampal beta2 coherence during AS was substantially reduced. These results demonstrate the necessity of sensory input, particularly during AS, for coordinating rhythmic activity between these two developing forebrain structures.