Vigilance States Research Articles

Sleep pattern in the dromedary camel: a behavioral and polysomnography study.

To investigate sleep patterns in the camel by combining behavioral and polysomnography (PSG) methods. A noninvasive PSG study was conducted over four nights on four animals. Additionally, video recordings were used to monitor the sleep behaviors associated with different vigilance states. During the night, short periods of sporadic sleep-like behavior corresponding to a specific posture, sternal recumbency (SR) with the head lying down on the ground, were observed. The PSG results showed rapid shifts between five vigilance states, including wakefulness, drowsiness, rapid eye movement (REM) sleep, non-REM (NREM) sleep, and rumination. The camels typically slept only 1.7 hours per night, subdivided into 0.5 hours of REM sleep and 1.2 hours of NREM sleep. Camels spent most of the night being awake (2.3 hours), ruminating (2.4 hours), or drowsing (1.9 hours). Various combinations of transitions between the different vigilance states were observed, with a notable transition into REM sleep directly from drowsiness (9%) or wakefulness (4%). Behavioral postures were found to correlate with PSG vigilance states, thereby allowing a reliable prediction of the sleep stage based on SR and the head position (erected, motionless, or lying down on the ground). Notably, 100% of REM sleep occurred during the Head Lying Down-SR posture. The camel is a diurnal species with a polyphasic sleep pattern at night. The best correlation between PSG and ethogram data indicates that sleep duration can be predicted by the behavioral method, provided that drowsiness is considered a part of sleep.

AN IN VITRO ANALYSIS AND ETHNOBOTANICAL PROFILE OF JASMINUM SAMBAC L.

The use of herbal drugs for prevention and treatment of various health ailments has been in practice since time immemorial. The main beauty and uniqueness of jasmine is its fragrance, which cannot be imitated by any known synthetic aromatic chemical and has a unique status in the perfume world. Apart from that inhaling Jasmine scent increases beta waves in the brain, which are associated with increases states of alertness. Various diseases like conjunctivitis, diarrhoea, abdominal pain and dermatitis are treated with its flowers along with roots and leaves are also utilized for curing pain, diarrhoea and fever. The present research is the highlight of various traditional uses as well as in vitro analysis reported till date from J. sambac. Regeneration of Maid of Orleans through direct and indirect organogenesis has been investigated.

REM Sleep Rebound Following Acute Intermittent Hypoxia in Freely Behaving Rats

Core components of the circadian clock and molecules involved in neuroplasticity elicited by acute intermittent hypoxia (AIH) exhibit 24‐hour rhythms in gene expression in the phrenic/diaphragm motor system. Ongoing investigations of time‐of‐day effects on AIH‐induced motor plasticity must account for changes in time spent across vigilance states since sleep architecture profoundly influences other biological rhythms across the rest‐active cycle. Previous investigations from our group reported a marginal increase in wakefulness during the AIH exposure in unanesthetized rats (10, 5‐min hypoxic episodes; 5 min intervals). Following AIH, we also observed a prolonged increase in slow‐wave sleep lasting hours, but changes in REM were not assessed (Terada et al., J. Appl. Physiol., 2011). Given the significant effects disruptions of the sleep‐wake cycle can have on daily biological rhythms, further characterization of sleep architecture following AIH is needed. In this preliminary analysis, from an extensive study of diaphragm long‐term facilitation (LTF) in rats at opposite stages of the diurnal cycle (mid‐active vs. mid‐rest), we added second set of intracortical EEG leads (ECoG) not used by Terada et al. (2011) to enhance detection of hippocampal theta bursts and sleep spindling. In 8 unanesthetized, instrumented rats exposed to AIH, ECoG, and nuchal EMG signals acquired via radiotelemetry were analyzed in 10‐second epochs using Fast Fourier transformation spectral analysis. Power spectra were averaged in frequency bands: delta (1.5‐4.0Hz), theta (4.0‐10.0Hz), beta (10.0‐30.0 Hz), and sigma (10.0‐14.0Hz). We assessed vigilance state at baseline, during AIH, and 90 minutes post‐AIH; there were significant effects of AIH protocol period (p < 0.05) and sleep state (p<0.001). There were marginal, non‐significant trends towards increased active wakefulness during AIH, with decreased quiet wakefulness, slow‐wave sleep, and REM. Time spent in REM sleep rebounded to levels nearly two‐fold above baseline at 60 and 90 min post‐AIH; there were non‐significant trends towards reduced quiet wakefulness without apparent change in NREM sleep post‐AIH. In this preliminary analysis, we report an acute AIH protocol (3, 5 min hypoxic episodes, 13% O2; 5‐min normoxic intervals) has minimal impact on NREM sleep during or following AIH but increases REM post‐AIH. Additional analyses will be performed during and following AIH during the mid‐active and mid‐rest phases, using the 5‐min AIH protocol and a modified protocol with similar cumulative duration of hypoxia (15, 1 min hypoxic episodes; 1 min intervals) often used in human studies of repetitive AIH as a neurotherapeutic modality to improve breathing and non‐respiratory motor function in humans living with chronic spinal cord injury and ALS. REM sleep is essential for mechanisms of neuroplasticity in neural networks controlling diverse physiological systems. These results warrant future research to delineate the influence REM may play in initiating and maintaining memory in the respiratory system.

The activation of C1 neurons during REM sleep is dependent on the arterial baroreflex

IntroductionNatural sleep‐wake patterns are associated with changes in sympathetic nerve activity (SNA) controlling cardiovascular function. The mechanisms underlying the effects of sleep‐wake state on SNA are not well understood. C1 neurons in the rostral ventrolateral medulla regulate cardiovascular function through SNA and mediate the sympathetic arterial baroreflex. In this study we determine the effect of sleep‐wake transitions on the activity of C1 neurons and investigate the contribution of the arterial baroreflex to these effects.MethodsThe activity of C1 neurons was measured using fiber photometry (calcium imaging) in freely behaving adult rats while monitoring the vigilance states. C1 neurons were targeted with GCaMP7s by microinjection of AAV1‐syn‐FLEX‐jGCaMP7s in the RVLM of Tyrosine Hydroxylase‐Cre transgenic rats, an optical fiber was implanted above the injection site, rats were fitted with a EEG/EMG head stage to monitor sleep‐wake state, and a radio telemetry probe to record BP. One month after the surgery, C1 neuron activity was recorded before and 7 days after sino‐aortic denervation to eliminate inputs from arterial baroreflex. Normalized fluorescence changes are expressed as Z‐score (mean ± SD) and t‐test was used to determine statistically significant differences.ResultsC1 activity was increased by acute hypotension induced by sodium nitroprusside (2.1 ± 0.5 vs. ‐0.92 ± 0.4, p<0.0001, n=5), indicating the barosensitive nature of the recorded cells. C1 activity increased during transitions from NREM to wake (‐0.60 ± 0.1 vs. 0.59 ± 0.2, p<0.0001, n=6) and decreased during transitions from wake to NREM (0.34 ± 0.2 vs. ‐0.32 ± 0.2, p<0.0001, n=6). C1 activity increased during transitions from NREM to REM sleep (‐0.74 ± 0.1 vs. 0.77 ± 0.1, p<0.0001, n=6) and decreased in transitions from REM to wake (0.58 ± 0.2 vs. ‐0.59 ± 0.2, p<0.0001, n=5). Baroreceptor denervation attenuates the increase in C1 neuron activity during REM sleep (0.4 ± 0.7 vs1.8 ± 0.4 Δ Z‐score, p=0.0054, n=4) and during wakefulness (0.59 ±0.6 vs 1.6 ± 0.4, p=0.0210, n=4) when compared to the increase before sino‐aortic denervation.ConclusionC1 neuron activity during sleep‐wake transitions mirrors the pattern of SNA. This observation indicates that C1 neurons contribute to changes in SNA associated with natural sleep‐wake patterns. Baroreceptor denervation attenuates the change in C1 activity observed during transitions to REM, indicating that the feedback from the arterial baroreflex contributes to the elevation in C1 activity in this sleep state.

Orexin A enhances neuronal synchronization in adult rat hypothalamic culture: A model to study hypothalamic function

BackgroundThe regulation of sleep/wake behavior and energy homeostasis is maintained in part by the lateral hypothalamic (LH) neuropeptide orexin A (OXA, hypocretin). A reduction in orexin signaling is associated with sleep disorders and obesity, whereas higher LH orexin signaling and sensitivity promotes obesity resistance. Similarly, dysregulation of hypothalamic neural networks is associated with onset of age‐related diseases, including obesity and several neurological diseases. Despite the increase in obesity with aging, and that adult populations are the subjects in the majority of pharmaceutical and obesity studies, conventional models for neuronal networks utilize embryonic neural cultures rather than adult neurons. Synchronous activity, a feature of normal brain function, and a measure of functional connectivity, describes correlated changes in neuronal activity between neurons, Synchronization determines the nature of the final output from a given neural structure. Neural synchrony is altered by behavioral perturbations, in embryonic neurons obtained from obesity‐resistant rats, and following application of OXA onto embryonic hypothalamic cultures. Synchronous network dynamics in adult hypothalamic neurons remain largely undescribed.MethodsWe established an adult rat hypothalamic culture in multi‐electrode‐array (MEA) dishes and recorded the field potentials. Then we studied the effect of exogenous OXA on network synchronization of these adult hypothalamic cultures. In addition, we studied the wake promoting effects of OXA in vivo when directly injected into the rostral lateral hypothalamus (rLH). To study the wake promoting effects of LH OXA, rats were implanted with a radiotelemetric transmitter and EEG/EMG electrodes to record vigilance states (F40‐EET, Data Sciences International [DSI], St. Paul, MN), and a cannula targeting the rLH. Following surgical recovery, either OXA (250 pmol/0.5 μl) or saline was infused into the rLH (single injection) and sleep/wake states were measured for 2h post‐injection.ResultsThe results show that adult hypothalamic cultures are viable for nearly 3 months in vitro, good quality MEA recordings can be obtained from these cultures in vitro, and finally, that cultured adult hypothalamus is responsive to OXA. In addition, LH administration of OXA enhanced wakefulness in rats, indicating that OXA enhances wakefulness for up to 2h post‐injection.ConclusionsThese results support that adult rat hypothalamic cultures could be used as a model to study the neural mechanisms underlying obesity, and that obesity resistance is associated with increased hypothalamus synchronization. Increased wake following rLH OXA suggest the possibility that OXA promotes wake partly by promoting neural synchrony in the hypothalamus.

Changes in striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence in male and female mice

Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors like irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during abstinence in a mouse model of chronic THC exposure. Using a THC treatment regimen known to produce tolerance, we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance to THC. Altered striatal DA release, sleep, and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. These findings provide a foundation for preclinical study of directly translatable non-precipitated THC withdrawal symptoms and the neural mechanisms that affect them.

Contribution of astrocytic histamine N-methyltransferase to histamine clearance and brain function in mice

Brain histamine acts as a neurotransmitter in the regulation of various brain activities. Previous studies have shown that histamine N-methyltransferase (HNMT), a histamine-metabolizing enzyme, controls brain histamine concentration and brain function. However, the relative contribution of astrocytic or neuronal HNMT to the regulation of the histaminergic system is still inconclusive. Here, we phenotyped astrocytes-specific HNMT knockout (cKO) mice to clarify the involvement of astrocytic HNMT in histamine clearance and brain function.First, we performed histological examinations using HNMT reporter mice and showed a wide distribution of HNMT in the brain and astrocytic HNMT expression. Then, we created cKO mice by Cre-loxP system and confirmed that HNMT expression in cKO primary astrocytes was robustly decreased. Although total HNMT level in the cortex was not substantially different between control and cKO brains, histamine concentration after histamine release was elevated in cKO cortex. In behavioral tests, impaired motor coordination and lower locomotor activity were observed in the cKO mice. However, anxiety-like behaviors, depression-like behaviors, and memory functions were not altered by astrocytic HNMT disruption. Although sleep analysis demonstrated that the quantity of wakefulness and sleep did not change, the increased power density of delta frequency during wakefulness indicated lower cortical activation in cKO mice. These results demonstrate that astrocytic HNMT contributes to histamine clearance after histamine release in the cortex and plays a role in the regulation of motor coordination, locomotor activity, and vigilance state.

Effects of sex and estrous cycle on sleep and cataplexy in narcoleptic mice.

Narcolepsy type 1 (NT1) is a rare neurology disorder caused by the loss of orexin/hypocretin neurons. NT1 is characterized by excessive daytime sleepiness, sleep and wake fragmentation, and cataplexy. These symptoms have been equally described in both women and men, although influences of gender and hormonal cycles have been poorly studied. Unfortunately, most studies with NT1 preclinical mouse models, use only male mice to limit potential variations due to the hormonal cycle. Therefore, whether gender and/or hormonal cycles impact the expression of narcoleptic symptoms remains to be determined. To address this question, we analyzed vigilance states and cataplexy in 20 female and 17 male adult orexin knock-out narcoleptic mice, with half of the females being recorded over multiple days. Mice had access to chocolate to encourage the occurrence of cataplectic episodes. A vaginal smear was performed daily in female mice to establish the state of the estrous cycle (EC) of the previous recorded night. We found that vigilance states were more fragmented in males than females, and that females had less paradoxical sleep (p = 0.0315) but more cataplexy (p = 0.0375). Interestingly, sleep and wake features were unchanged across the female EC, but the total amount of cataplexy was doubled during estrus compared to other stages of the cycle (p = 0.001), due to a large increase in the number of cataplexy episodes (p = 0.0002). Altogether these data highlight sex differences in the expression of narcolepsy symptoms in orexin knock-out mice. Notably, cataplexy occurrence was greatly influenced by estrous cycle. Whether it is due to hormonal changes would need to be further explored.

Improved Cognitive Vigilance Assessment after Artifact Reduction with Wavelet Independent Component Analysis.

Vigilance level assessment is of prime importance to avoid life-threatening human error. Critical working environments such as air traffic control, driving, or military surveillance require the operator to be alert the whole time. The electroencephalogram (EEG) is a very common modality that can be used in assessing vigilance. Unfortunately, EEG signals are prone to artifacts due to eye movement, muscle contraction, and electrical noise. Mitigating these artifacts is important for an accurate vigilance level assessment. Independent Component Analysis (ICA) is an effective method and has been extensively used in the suppression of EEG artifacts. However, in vigilance assessment applications, it was found to suffer from leakage of the cerebral activity into artifacts. In this work, we show that the wavelet ICA (wICA) method provides an alternative for artifact reduction, leading to improved vigilance level assessment results. We conducted an experiment in nine human subjects to induce two vigilance states, alert and vigilance decrement, while performing a Stroop Color–Word Test for approximately 45 min. We then compared the performance of the ICA and wICA preprocessing methods using five classifiers. Our classification results showed that in terms of features extraction, the wICA method outperformed the existing ICA method. In the delta, theta, and alpha bands, we obtained a mean classification accuracy of 84.66% using the ICA method, whereas the mean accuracy using the wICA methodwas 96.9%. However, no significant improvement was observed in the beta band. In addition, we compared the topographical map to show the changes in power spectral density across the brain regions for the two vigilance states. The proposed method showed that the frontal and central regions were most sensitive to vigilance decrement. However, in this application, the proposed wICA shows a marginal improvement compared to the Fast-ICA.

Automatic Neonatal Alertness State Classification Based on Facial Expression Recognition

Premature babies are admitted to the neonatal intensive care unit (NICU) for several weeks and are generally placed under high medical supervision. The NICU environment is considered to have a bad influence on the formation of the sleep-wake cycle of the neonate, known as the circadian rhythm, because patient monitoring and treatment equipment emit light and noise throughout the day. In order to improve the neonatal environment, researchers have investigated the effect of light and noise on neonates. There are some methods and devices to measure neonatal alertness, but they place on additional burden on neonatal patients or nurses. Therefore, this study proposes an automatic non-contact neonatal alertness state classification method using video images. The proposed method consists of a face region of interest (ROI) location normalization method, histogram of oriented gradients (HOG) and gradient feature-based feature extraction methods, and a neonatal alertness state classification method using machine learning. Comparison experiments using 14 video images of 7 neonatal subjects showed that the weighted support vector machine (w-SVM) using the HOG feature and averaging merge achieved the highest classification performance (micro-F1 of 0.732). In clinical situations, body movement is evaluated primarily to classify waking states. The additional 4 class classification experiments are conducted by combining waking states into a single class, with results that suggest that the proposed facial expression based classification is suitable for the detailed classification of sleeping states.

Sexuality and Sleep Disorders

The physiological role of sleep in the maintenance of number of life function including development, energy conservation, brain waste clearance, modulation of immune responses, cognition, performance, vigilance, disease, and psychological state is well documented in the scientific literature.1-3 Sexual activity and sleep are both considered as “dyadic events” (at least for partners who share the same bedroom) and there is also a physiological pattern that leads from the first to the second one. Orgasm is followed by a parasympathetic discharge, psychological and physical relaxation that all together promote sleep.

Distinct and diverse chromatin proteomes of ageing mouse organs reveal protein signatures that correlate with physiological functions.

Temporal molecular changes in ageing mammalian organs are of relevance to disease aetiology because many age-related diseases are linked to changes in the transcriptional and epigenetic machinery that regulate gene expression. We performed quantitative proteome analysis of chromatin-enriched protein extracts to investigate the dynamics of the chromatin proteomes of the mouse brain, heart, lung, kidney, liver, and spleen at 3, 5, 10, and 15 months of age. Each organ exhibited a distinct chromatin proteome and sets of unique proteins. The brain and spleen chromatin proteomes were the most extensive, diverse, and heterogenous among the six organs. The spleen chromatin proteome appeared static during the lifespan, presenting a young phenotype that reflects the permanent alertness state and important role of this organ in physiological defence and immunity. We identified a total of 5928 proteins, including 2472 nuclear or chromatin-associated proteins across the six mouse organs. Up to 3125 proteins were quantified in each organ, demonstrating distinct and organ-specific temporal protein expression timelines and regulation at the post-translational level. Bioinformatics meta-analysis of these chromatin proteomes revealed distinct physiological and ageing-related features for each organ. Our results demonstrate the efficiency of organelle-specific proteomics for in vivo studies of a model organism and consolidate the hypothesis that chromatin-associated proteins are involved in distinct and specific physiological functions in ageing organs.

Effect of Sleep on Epileptic Discharges in Patients with Idiopathic Generalized Epilepsy.

Background. It is known that sleep and sleep deprivation affect the EEG findings, onset, frequency and semiology of the seizures. Generalized spike and wave discharges were found more common in drowsiness and sleep states, especially in childhood and juvenile absence epilepsy syndromes. Aim. In this study we aimed to show the effects of short sleep on the interictal and ictal discharges of the patients with genetic generalized epileptic seizures and to show the effects of treatment on the discharges during awake and sleep states. Method. 37 patients (29 females and 8 males) with a diagnosis of genetic generalized epilepsy syndrome were included. All the patients were investigated with video-EEG recording during awake, sleep and post sleep states. Epileptic discharges were counted manually. Discharge numbers and their relation with triggers were analyzed to see the difference between different vigilance states. Results. Number of ictal discharges is found to be increased after sleep. There was no difference in the control EEGs, which were taken under treatment. Conclusion. Sleep is a trigger of epileptic discharges in ictal nature, but an effective antiepileptic treatment prevents this effect.

Somatovisceral Convergence in Sleep-Wake Cycle: Transmitting Different Types of Information via the Same Pathway.

Convergence of somatic and visceral inputs occurs at the levels of nervous system ranging from spinal cord to cerebral cortex. This anatomical organization gave explanation to a referred pain phenomenon. However, it also presents a problem: How does the brain know what information is coming for processing-somatic or visceral - if both are transferred by the same spinal cord fibers by means of the standard neuronal spikes? Recent studies provided evidence for cortical processing of interoceptive information largely occurring in sleep, when somatosensation is suppressed, and for the corresponding functional brain networks rearrangement. We suggest that convergent units of the spinal cord would be able to collectively provide mainly somatosensory information in wakefulness and mainly visceral in sleep, solving the puzzle of somatovisceral convergence. We recorded spiking activity from the spinal cord lemniscus pathway during multiple sleep-wake cycles in freely behaving rabbits. In wakefulness high increased spiking corresponded to movements. When animals stopped moving this activity ceased, the fibers remained silent during passive wakefulness. However, upon transition to sleep fibers began firing again. Analysis of spiking patterns of individual fibers revealed that in the majority of them spiking rates recovered in slow wave sleep. Thus, despite cessation of motion and a corresponding decrease of somatic component of the convergent signal, considerable ascending signaling occurs during sleep, that is likely to be visceral. We also recorded evoked responses of the lemniscus pathway to innocuous electrostimulation of the abdominal viscera, and uncovered the existence of two groups of responses depending upon the state of vigilance. Response from an individual fiber could be detected either during wakefulness or in sleep, but not in both states. Wakefulness-responsive group had lower spiking rates in wakefulness and almost stopped spiking in sleep. Sleep-responsive retained substantial spiking during sleep. These groups also differed in spike amplitudes, indicative of fiber diameter differences; however, both had somatic responses during wakefulness. We suggest a mechanism that utilizes differences in somatic and visceral activities to extract both types of information by varying transmission thresholds, and discuss the implications of this mechanism on functional networks under normal and pathological conditions.

The impact of tethered recording techniques on activity and sleep patterns in rats

Electrophysiological recordings in animals constitute frequently applied techniques to study neuronal function. In this context, several authors described tethered recordings as a semi-restraint situation with negative implications for animal welfare and suggested radiotelemetric setups as a refinement measure. Thus, we here investigated the hypothesis that tethered recordings exert measurable effects on behavioral and sleep patterns in Sprague–Dawley rats. Animals were kept in monitoring glass cages either with or without a head connection to a recording cable. Saccharin preference, nest building, serum corticosterone and fecal corticosterone metabolite levels were in a comparable range in both groups. The proportion of vigilance states was not affected by the cable connection. Minor group differences were detected in bout lengths distributions, with a trend for longer NREM and WAKE stages in animals with a cable connection. However, a relevant effect was not further confirmed by an analysis of the number of sleep/wake and wake/sleep transitions. The analysis of activity levels did not reveal group differences. However, prolonged exposure to the tethered condition resulted in an intra-group increase of activity. In conclusion, the comparison between freely moving vs tethered rats did not reveal major group differences. Our findings indicate that telemetric recordings only offer small advantages vs cabled set ups, though this may differ in other experimental studies where for example anxiety- or drug-induced effects are analyzed.

Decoding the potential of a new Pseudomonas putida strain for inducing drought tolerance of tomato (Solanum lycopersicum) plants through seed biopriming

A total of 11 potential plant growth promoting rhizobacteria previously isolated from naturally stressed environments were evaluated for various traits of interest for a beneficial symbiosis with plants, including colonization ability, biofilm formation, motility, exopolysaccharide production and salt tolerance. The vast majority of the strains were found to possess multiple plant growth promoting traits. Nevertheless, the intensity varied among isolates, with those originated from tomato plants being more efficient colonizers. The strain SAESo11, genetically characterized as a Pseudomonas putida member was selected for further investigation of its potential to alleviate drought stress in tomato seedlings. Inoculation with SAESo11 mitigated the negative effects of drought stress as indicated by growth and photosynthetic indices. Furthermore, bacterial inoculation enhanced H2O2 content and malondialdehyde levels in colonized plants. Drought treatment did not further alter the oxidative status of these plants. Similarly, total phenolic content and antioxidant enzyme activity were induced in plant tissues in response to drought stress only at the absence of inoculum. These results indicated that inoculation with the selected strain imposed plants at a priming state, that enabled them to respond more robustly at the exposure to drought stress and efficiently attenuated the drought-induced injury. This state of plant alertness mediated by SAESo11 occurred at no cost to growth, highlighting its role as a potential plant priming agent.

Psilocin acutely alters sleep-wake architecture and cortical brain activity in laboratory mice

Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the homeostatic regulation of neuronal activity and synaptic plasticity. However, it remains largely unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 h after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow-wave activity. However, psilocin decreased the recovery rate of sleep slow-wave activity following sleep deprivation in the local field potentials of electrodes targeting the medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.

OC16: Electro-clinical features in epileptic children with chromosome 15qduplication syndrome

We aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15). Methods: Clinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5m.oto 17y4m (median follow-up 8y3m), were retrospectively reviewed. EEGs were analyzed visually and using power spectrum analysis. Results: Seventy video-EEGs were analyzed (1-16 per patient, median 6), follow-up lasting up to 8y10m (median 4y2m): 25 EEGs in intdup15(8m.o to 12y.o, median 4y6m) and 45 EEGs in idic15 (7m.o to 12 y.o, median 15m).Epilepsy: 6 Westsyndrome (WS) (2intdup15, 4idic15);4 Lennox-Gastaut syndromes (LGS) (1 intdup15, 3 idic15), 2 evolving from WS; focal epilepsy (3 intdup15). In idic15, WS displayed additional myoclonic seizures (3), atypical (4) or no hypsarrhythmia (2) and posterior predominant spike and polyspike bursts (4). Beta-bandrapid-rhythms (RR):present in 11 patients, power decreased during non-REM-sleep, localization shifted from diffuse to anterior, peak frequency increased with age. Conclusion: WS with peculiar electro-clinical features and LGS, along with beta-band RR decreasing in non-REM-sleep and shifting from diffuse to anterior localization with age are recognizable features pointing towards dup15q diagnosis in children with autism spectrum disorder and developmental delay. This study describes electroclinical features in both interstitial and isodicentric duplications of chromosome 15q, in epileptic children, including some recent extensions regarding sleep features; and illustrates how the temporo-spatial organization of beta oscillations can be of significant help in directing towards dup15q diagnosis hypothesis.

Predicting the loss of responsiveness when falling asleep in humans

Falling asleep is a dynamical process that is poorly defined. The period preceding sleep, characterized by the progressive alteration of behavioral responses to the environment, which may last several minutes, has no electrophysiological definition, and is embedded in the first stage of sleep (N1). We aimed at better characterizing this drowsiness period looking for neurophysiological predictors of responsiveness using electro and magneto-encephalography. Healthy participants were recorded when falling asleep, while they were presented with continuous auditory stimulations and asked to respond to deviant sounds. We analysed brain responses to sounds and markers of ongoing activity, such as information and connectivity measures, in relation to rapid fluctuations of brain rhythms observed at sleep onset and participants’ capabilities to respond. Results reveal a drowsiness period distinct from wakefulness and sleep, from alpha rhythms to the first sleep spindles, characterized by diverse and transient brain states that come on and off at the scale of a few seconds and closely reflects, mainly through neural processes in alpha and theta bands, decreasing probabilities to be responsive to external stimuli. Results also show that the global P300 was only present in responsive trials, regardless of vigilance states. A better consideration of the drowsiness period through a formalized classification and its specific brain markers such as described here should lead to significant advances in vigilance assessment in the future, in medicine and ecological environments.

Deep brain electrophysiology in freely moving sheep

Although rodents are arguably the easiest animals to use for studying brain function, relying on them as model species for translational research comes with its own set of limitations. Here, we propose sheep as a practical large animal species to use for invivo brain function studies performed in naturalistic settings. We conducted proof-of-principle deep brain electrophysiological recording experiments using unrestrained sheep during behavioral testing. Recordings were made from cortex and hippocampus, both while sheep performed goal-directed behaviors (two-choice discrimination tasks) and across states of vigilance, including sleep. Hippocampal and cortical oscillatory rhythms were consistent with those seen in rodents and non-human primates, and included cortical alpha oscillations and hippocampal sharp wave ripple oscillations (∼150Hz) during immobility and hippocampal theta oscillations (5-6Hz) during locomotion. Recordings were conducted over a period of many months during which time the animals participated willingly in the experiments. Over 3,000 putative neurons were identified, including examples whose activity was modulated by task, speed of locomotion, spatial position, reward and vigilance states, and one whose firing rate was potentially modulated by the sight of the investigator. Together, these experiments demonstrate that sheep are excellent experimental animals to use for longitudinal studies requiring a large-brained mammal and/or large-scale recordings across distributed neuronal networks. Sheep could be used safely for studying not only neural encoding of decision-making and spatial-mapping in naturalisticenvironments outside the confines of the traditional laboratory but also the neural basis of both intra- and inter-species social interactions.