Neuroligin-2 shapes individual slow waves during slow-wave sleep and the response to sleep deprivation in mice.

Background: Sleep disturbances are a common comorbidity to most neurodevelopmental disorders and tend to worsen disease symptomatology. It is thus crucial to understand mechanisms underlying sleep disturbances to improve patients' quality of life. Neuroligin-2 (NLGN2) is a synaptic adhesion protein regulating GABAergic transmission.

Cortical links glutamatergic signaling to NREM sleep EEG slow waves in an activity-dependent manner.

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that have been implicated in a plethora of neuronal processes. Nevertheless, their role in regulating brain activity in the context of sleep has so far received little attention. To test their involvement, we deleted mature miRNAs in post-mitotic neurons at two developmental ages, i.

Characterization of Sleep, Emotional, and Cognitive Functions in a New Rat Model of Concomitant Spinal Cord and Traumatic Brain Injuries.

Traumatic injuries to the spinal cord or the brain have serious medical consequences and lead to long-term disability. The epidemiology, medical complications, and prognosis of isolated spinal cord injury (SCI) and traumatic brain injury (TBI) have been well described. However, there are limited data on patients suffering from concurrent SCI and TBI, even if a large proportion of SCI patients have concomitant TBI.

Sleep-inducing effect of Rhynchophylline in knockout mice.

We have recently demonstrated that the alkaloid rhynchophylline (RHY; purified from plants) induces sleep and modifies electrocorticographic (ECoG) activity throughout the 24-h day in a vigilance state-dependent manner in wild-type mice. We here asked whether this alkaloid impacts wake/sleep variables in the absence of the cell adhesion protein EPHA4, via ECoG recording in knockout (KO) mice submitted to the same RHY treatment contemporaneously to the wild-type mice (littermates). We uncover that RHY decreases time spent awake and increases time spent in slow wave sleep in KO mice and alters the 24-h time course of ECoG activity during wakefulness and sleep states.

Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats.

Background: Soluble amyloid-beta oligomers (Aβo) begin to accumulate in the human brain one to two decades before a clinical diagnosis of Alzheimer's disease (AD). The literature supports that soluble Aβo are implicated in synapse and neuronal losses in the brain regions such as the hippocampus. This region importantly contributes to explicit memory, the first type of memory affected in AD.

Transcriptional regulation of the mouse , and genes by the circadian clock machinery.

Circadian rhythms originate from molecular feedback loops. In mammals, the transcription factors CLOCK and BMAL1 act on regulatory elements (i.e.

Probing pathways by which rhynchophylline modifies sleep using spatial transcriptomics.

Background: Rhynchophylline (RHY) is an alkaloid component of Uncaria, which are plants extensively used in traditional Asian medicines. Uncaria treatments increase sleep time and quality in humans, and RHY induces sleep in rats. However, like many traditional natural treatments, the mechanisms of action of RHY and Uncaria remain evasive.

Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation.

is a plant highly used in the traditional Chinese and Japanese medicines. It has numerous health benefits, which are often attributed to its alkaloid components. Recent studies in humans show that drugs containing ameliorate sleep quality and increase sleep time, both in physiological and pathological conditions.

A review of the current state of knowledge on sex differences in sleep and circadian phenotypes in rodents.

Sleep is a vital part of our lives as it is required to maintain health and optimal cognition. In humans, sex differences are relatively well-established for many sleep phenotypes. However, precise differences in sleep phenotypes between male and female rodents are less documented.

Electrocorticographic Recording of Cerebral Cortex Areas Manipulated Using an Adeno-Associated Virus Targeting Cofilin in Mice.

The use of electrocorticographic (ECoG) recordings in rodents is relevant to sleep research and to the study of a wide range of neurological conditions. Adeno-associated viruses (AAVs) are increasingly used to improve understanding of brain circuits and their functions. The AAV-mediated manipulation of specific cell populations and/or of precise molecular components has been tremendously useful to identify new sleep regulatory circuits/molecules and key proteins contributing to the adverse effects of sleep loss.

Fxr1 regulates sleep and synaptic homeostasis.

The fragile X autosomal homolog 1 (Fxr1) is regulated by lithium and has been GWAS-associated with schizophrenia and insomnia. Homeostatic regulation of synaptic strength is essential for the maintenance of brain functions and involves both cell-autonomous and system-level processes such as sleep. We examined the contribution of Fxr1 to cell-autonomous homeostatic synaptic scaling and neuronal responses to sleep loss, using a combination of gene overexpression and Crispr/Cas9-mediated somatic knockouts to modulate gene expression.

A case report of severe tuberous sclerosis complex detected in utero and linked to a novel duplication in the TSC2 gene.

Background: Disease severity is tremendously variable in tuberous sclerosis complex (TSC). In contrast with the detailed guidelines available for TSC diagnosis and management, clinical practice lacks adequate tools to evaluate the prognosis, especially in the case of in utero diagnosis. In addition, the correlation between genotypes and phenotypes remains a challenge, in part due to the large number of mutations linked to TSC.

Rapid fast-delta decay following prolonged wakefulness marks a phase of wake-inertia in NREM sleep.

Sleep-wake driven changes in non-rapid-eye-movement sleep (NREM) sleep (NREMS) EEG delta (δ-)power are widely used as proxy for a sleep homeostatic process. Here, we noted frequency increases in δ-waves in sleep-deprived mice, prompting us to re-evaluate how slow-wave characteristics relate to prior sleep-wake history. We identified two classes of δ-waves; one responding to sleep deprivation with high initial power and fast, discontinuous decay during recovery sleep (δ2) and another unrelated to time-spent-awake with slow, linear decay (δ1).

Neuroligin-1 is altered in the hippocampus of Alzheimer's disease patients and mouse models, and modulates the toxicity of amyloid-beta oligomers.

Synapse loss occurs early and correlates with cognitive decline in Alzheimer's disease (AD). Synaptotoxicity is driven, at least in part, by amyloid-beta oligomers (Aβo), but the exact synaptic components targeted by Aβo remain to be identified. We here tested the hypotheses that the post-synaptic protein Neuroligin-1 (NLGN1) is affected early in the process of neurodegeneration in the hippocampus, and specifically by Aβo, and that it can modulate Aβo toxicity.

Circadian and sleep/wake-dependent variations in tau phosphorylation are driven by temperature.

Study Objectives: Aggregates of hyperphosphorylated tau protein are a hallmark of Alzheimer's disease (AD) and other tauopathies. Sleep disturbances are common in AD patients, and insufficient sleep may be a risk factor for AD. Recent evidence suggests that tau phosphorylation is dysregulated by sleep disturbances in mice.

Wakefulness/sleep architecture and electroencephalographic activity in mice lacking the translational repressor 4E-BP1 or 4E-BP2.

Sleep and sleep loss are affecting protein synthesis in the brain, but the contribution of translational control to wakefulness and sleep regulation remains poorly understood. Here, we studied the role of two suppressors of protein synthesis, the eukaryotic translation initiation factor 4E-binding proteins 1 and 2 (4E-BP1 and 4E-BP2), in sleep architecture and electroencephalographic (EEG) activity as well as in the EEG and molecular responses to acute sleep loss. The EEG of mice mutant for the genes encoding 4E-BP1 or 4E-BP2 (Eif4ebp1 and Eif4ebp2 knockout [KO] mice) was recorded under undisturbed conditions and following a 6-hour sleep deprivation (SD).

Correction to: The effect of Neuroligin-2 absence on sleep architecture and electroencephalographic activity in mice.

Correction to: Molecular Brain (2018) 11:52 https://doi.org/10.1186/s13041-018-0394-3Following publication of the original article [1], the authors reported that the article was mistakenly submitted with the omission of two authors: Feng Cao and Zhengping Jia.

Transcriptional control of synaptic components by the clock machinery.

Circadian rhythms are generated in mammals by a central clock located in the suprachiasmatic nucleus of the hypothalamus, which regulates the homeostasis of many biological processes. At the molecular level, the regulation of circadian rhythms is under the control of transcriptional-translational feedback loops composed of clock factors, including transcription factors. In the brain, synaptic plasticity has been shown to vary with a 24-h rhythm.

Scale-Free Dynamics of the Mouse Wakefulness and Sleep Electroencephalogram Quantified Using Wavelet-Leaders.

Scale-free analysis of brain activity reveals a complexity of synchronous neuronal firing which is different from that assessed using classic rhythmic quantifications such as spectral analysis of the electroencephalogram (EEG). In humans, scale-free activity of the EEG depends on the behavioral state and reflects cognitive processes. We aimed to verify if fractal patterns of the mouse EEG also show variations with behavioral states and topography, and to identify molecular determinants of brain scale-free activity using the 'multifractal formalism' (Wavelet-Leaders).

The effect of Neuroligin-2 absence on sleep architecture and electroencephalographic activity in mice.

Sleep disorders are comorbid with most psychiatric disorders, but the link between these is not well understood. Neuroligin-2 (NLGN2) is a cell adhesion molecule that plays roles in synapse formation and neurotransmission. Moreover, NLGN2 has been associated with psychiatric disorders, but its implication in sleep remains underexplored.

Bidirectional relationships between sleep and amyloid-beta in the hippocampus.

Alzheimer's disease (AD) is a debilitating neurodegenerative disease characterized by progressive hippocampal-dependent explicit memory deficits that begin at the onset of the illness. An early hallmark of AD is the accumulation of amyloid-beta (Aß) proteins in brain structures involved in encoding and consolidation of memory, like the hippocampus and prefrontal cortex. Aß neurotoxicity is known to induce synaptic dysfunctions and neuronal death leading to cognitive decline.

Omics Approaches in Sleep-Wake Regulation.

Although sleep seems an obvious and simple behaviour, it is extremely complex involving numerous interactions both at the neuronal and the molecular levels. While we have gained detailed insight into the molecules and neuronal networks responsible for the circadian organization of sleep and wakefulness, the molecular underpinnings of the homeostatic aspect of sleep regulation are still unknown and the focus of a considerable research effort. In the last 20 years, the development of techniques allowing the simultaneous measurement of hundreds to thousands of molecular targets (i.

Regulation of the Neuroligin-1 Gene by Clock Transcription Factors.

NEUROLIGIN-1 (NLGN1) is a postsynaptic adhesion molecule involved in the regulation of glutamatergic transmission. It has been associated with several features of sleep and psychiatric disorders. Our previous work suggested that transcription of the Nlgn1 gene could be regulated by the transcription factors CLOCK and BMAL1 because they bind to the Nlgn1 gene promoter in vivo.

DNA methylation and transcription onset in the brain.

Aim: The goal of this study was to test the state of methylation of transcription start positions in DNA that are actively involved in transcription.

Materials & Methods: We used sequential ChIP-bisulfite-sequencing with an antibody to RNpolII-PS5 to map the state of methylation of actively transcribing transcription start sites (TSS).

Results: TSS that RNApolII-PS5 physically bind to, are ubiquitously unmethylated.