Pharmacological Effect of Verapamil on Brain Oxidative Parameters and Mania-Like Behaviour in Paradoxical Sleep Deprived Mice

Although the implication of calcium signalling in the aetiology of anxiety remains elusive, drugs modulating calcium (like calcium channel blockers) have been discovered to be some worth beneficial as treatment option for anxiety related disorders. This study was therefore undertaken to assess probable ameliorative potential of verapamil against manic-like (stereotype behaviour) and anxiety-like symptoms in mice exposed to sleep deprivation. Mice were allotted into five treatment groups (n=5): group 1 and 2 received 10 mL/kg distilled water, groups 3 and 4 verapamil (25 and 50 mg/kg) while group 5 received astaxanthin (50 mg/kg) which served as the reference drug. Treatment was for 7 days and animals were sleep-deprived on the final 72 hours. Various behavioural tests to determine degree of stereotypical behaviour and locomotor activity were carried out. Anxiety test was done via the aid of a light/dark box and plus maze while stereotype behaviour was assess utilizing an open field box. Oxidative stress parameters; malondialdehyde and glutathione were assessed. Histopathological perturbations in the caudate putamen were also recorded. Data were subjected to ANOVA at α0.05. The results obtained suggest that verapamil significantly suppressed stereotyped behaviour and reduced the incidence of manic-like behaviour which was induced by paradoxical sleep deprivation. Verapamil also significantly restored antioxidant levels and protected against loss of caudate neurons. In conclusion, verapamil ameliorates manic-like symptoms and anxiety in mice derived of sleep, while protecting brain neurons against oxidative stress damage induced by sleep deprivation.

Global dissociation of the amygdala from the rest of the brain during REM sleep

Rapid-eye-movement sleep (REMS) or paradoxical sleep is associated with intense neuronal activity, fluctuations in autonomic control, body paralysis and brain-wide hyperemia. The mechanisms and functions of these energy-demanding patterns remain elusive and a global picture of brain activation during REMS is currently missing. In the present work, we performed functional ultrasound (fUS) imaging at the whole-brain scale during hundreds of REMS episodes to provide the spatiotemporal dynamics of vascular activity in 259 brain regions spanning more than 2/3 of the total brain volume. We first demonstrate a dissociation between basal/midbrain and cortical structures, the first ones sustaining tonic activation during REMS while the others are activated in phasic bouts. Second, we isolated the vascular compartment in our recordings and identified arteries in the anterior part of the brain as strongly involved in the blood supply during REMS episodes. Finally, we report a peculiar activation pattern in the amygdala, which is strikingly disconnected from the rest of the brain during most but not all REMS episodes. This last finding shows that amygdala undergoes specific processing during REMS and may be linked to the regulation of emotions and the creation of dream content during this very state.

Global dissociation of the amygdala from the rest of the brain during REM sleep

Rapid-eye-movement sleep (REMS) or paradoxical sleep is associated with intense neuronal activity, fluctuations in autonomic control, body paralysis and brain-wide hyperemia. The mechanisms and functions of these energy-demanding patterns remain elusive and a global picture of brain activation during REMS is currently missing. In the present work, we performed functional ultrasound (fUS) imaging at the whole-brain scale during hundreds of REMS episodes to provide the spatiotemporal dynamics of vascular activity in 259 brain regions spanning more than 2/3 of the total brain volume. We first demonstrate a dissociation between basal/midbrain and cortical structures, the first ones sustaining tonic activation during REMS while the others are activated in phasic bouts. Second, we isolated the vascular compartment in our recordings and identified arteries in the anterior part of the brain as strongly involved in the blood supply during REMS episodes. Finally, we report a peculiar activation pattern in the amygdala, which is strikingly disconnected from the rest of the brain during most but not all REMS episodes. This last finding shows that amygdala undergoes specific processing during REMS and may be linked to the regulation of emotions and the creation of dream content during this very state.

Sources of variation in the spectral slope of the sleep EEG

Building on previous work linking changes in the electroencephalogram (EEG) spectral slope to arousal level, Lendner et al. (2021) reported that wake, non rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep exhibit progressively steeper 30-45 Hz slopes, interpreted in terms of increasing cortical inhibition. Here we sought to replicate Lendner et al.'s scalp EEG findings (based on 20 individuals) in a larger sample of 11,630 individuals from multiple cohorts in the National Sleep Research Resource (NSRR). In a final analytic sample of N = 10,255 distinct recordings, there was unambiguous statistical support for the hypothesis that, within individuals, the mean spectral slope grows steeper going from wake to NREM to REM sleep. We found that the choice of mastoid referencing scheme modulated the extent to which electromyogenic or electrocardiographic artifacts were likely to bias 30-45 Hz slope estimates, as well as other sources of technical, device-specific bias. Nonetheless, within individuals, slope estimates were relatively stable over time. Both cross-sectionally and longitudinal, slopes tended to become shallower with increasing age, particularly for REM sleep; males tended to show flatter slopes than females across all states. Although conceptually distinct, spectral slope did not predict sleep state substantially better than other summaries of the high frequency EEG power spectrum (>20 Hz, in this context) including beta band power, however. Finally, to more fully describe sources of variation in the spectral slope and its relationship to other sleep parameters, we quantified state-dependent differences in the variances (both within and between individuals) of spectral slope, power and interhemispheric coherence, as well as their covariances. In contrast to the common conception of the REM EEG as relatively wake-like (i.e. 'paradoxical' sleep), REM and wake were the most divergent states for multiple metrics, with NREM exhibiting intermediate profiles. Under a simplified modelling framework, changes in spectral slope could not, by themselves, fully account for the observed differences between states, if assuming a strict power law model. Although the spectral slope is an appealing, theoretically inspired parameterization of the sleep EEG, here we underscore some practical considerations that should be borne in mind when applying it in diverse datasets. Future work will be needed to fully characterize state-dependent changes in the aperiodic portions of the EEG power spectra, which appear to be consistent with, albeit not fully explained by, changes in the spectral slope.

Peculiarities of neuroregulatory mechanisms of adaptation under alcohol dependence (experimental study)

Neurophysiological and biochemical markers of alcohol dependence were identified in a study conducted in laboratory rats at the systemic and molecular levels. It has been shown that long-term alcohol consumption is accompanied by an increase in dopamine levels in the ventral tegmental area and a decrease in GABA and BDNF levels in the hippocampus and serum and leads to attenuation of neocortex control of the limbic emotional-motivational system of the brain. Disturbance of the mechanisms of structural and functional organization of wake-sleep processes and regulation of emotional reactions, which is reflected in the suppression of slow-wave sleep, reduction of paradoxical sleep, inhibition of positive emotional centers, the development of anxiety and depression have been determined. Key words: alcohol dependence, sleep-wake, anxiety, depression, catecholamines, GABA, BDNF

The Human Sleep Paradox: The Unexpected Sleeping Habits of Homo sapiens

The human sleep pattern is paradoxical. Sleep is vital for optimal physical and cognitive performance, yet humans sleep the least of all primates. In addition, consolidated and continuous monophasic sleep is evidently advantageous, yet emerging comparative data sets from small-scale societies show that the phasing of the human pattern of sleep–wake activity is highly variable and characterized by significant nighttime activity. To reconcile these phenomena, the social sleep hypothesis proposes that extant traits of human sleep emerged because of social and technological niche construction. Specifically, sleep sites function as a type of social shelter by way of an extended structure of social groups that increases fitness. Short, high-quality, and flexibly timed sleep likely originated as a response to predation risks while sleeping terrestrially. This practice may have been a necessary preadaptation for migration out of Africa and for survival in ecological niches that penetrate latitudes with the greatest seasonal variation in light and temperature on the planet. Expected final online publication date for the Annual Review of Anthropology, Volume 50 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Granule cells in the infrapyramidal blade of the dentate gyrus are activated during paradoxical (REM) sleep hypersomnia but not during wakefulness: a study using TRAP mice

Study Objectives Determine whether in the hippocampus and the supramammillary nucleus (SuM) the same neurons are reactivated when mice are exposed one week apart to two periods of wakefulness (W-W), paradoxical sleep rebound (PSR-PSR) or a period of W followed by a period of PSR (W-PSR) Methods We combined the innovative TRAP2 mice method in which neurons expressing cFos permanently express tdTomato after tamoxifen injection with cFos immunohistochemistry. Results We found out that a large number of tdTomato+ and cFos+ cells are localized in the dentate gyrus (DG) after PSR and W while CA1 and CA3 contained both types of neurons only after W. The number of cFos+ cells in the infrapyramidal but not the suprapyramidal blade of the DG was positively correlated with the amount of PS. In addition, we did not find double-labeled cells in the DG whatever the group of mice. In contrast, a high percentage of CA1 neurons were double-labeled in W-W mice. Finally, in the supramammillary nucleus, a large number of cells were double-labeled in W-W, PSR-PSR but not in W-PSR mice. Conclusions Altogether, our results are the first to show that different neurons are activated during W and PS in the supramammillary nucleus and the hippocampus. Further, we showed for the first time that granule cells of the infrapyramidal blade of the DG are activated during PS but not during W. Further experiments are now needed to determine whether these granule cells belong to memory engrams inducing memory reactivation during PS.