Biology subjects

Mongrain, V.

Publications and source records attributed to Mongrain, V..

6 recordsLinked to original sources

bioRxiv2026

Assessing accelerometry as an alternative to electromyography for mouse sleep scoring

For sleep scoring in rodents, the use of electromyography (EMG) is considered the gold standard to assess muscle tone; however, EMG electrodes require invasive surgical implantation, are sensitive to muscular placement, can have extensive noise due to non-muscular signal contamination, and are at risk of failure due to mechanical stress. The use of an accelerometer (Acc) integrated on the recording headstage offers an alternative for movement detection. However, the degree of agreement between these two approaches has never been systematically evaluated. To understand if these tools allow similar scoring outcomes, seven trained scorers manually classified mouse sleep recordings using hippocampal local field potential (LFP) together with EMG or Acc. When comparing scoring between EMG and Acc, overall epoch-by-epoch accuracy exceeded 90% with a kappa score above 0.8, indicating excellent agreement. However, Acc was found to under classify Wake by 4.92% while overclassifying NREM sleep by 3.29%, possibly reflecting a decreased sensitivity of Acc to subtle changes in muscle tone used in distinguishing Wake from NREM sleep. Comparing EMG and Acc signal for agreed epochs vs disagreed epochs revealed a weaker correlation between the two signals for disagreed epochs, especially for Wake and NREM, suggesting that disagreements reflected genuine signal differences rather than scorer subjectivity. These findings support LFP/Acc as a valid approach to sleep scoring, however, it is noted that Acc based scoring slightly underestimated Wake epochs, favoring NREM sleep, relative to traditional EMG approach.

neuroscience↗

bioRxiv2025

Sex-dependent effects of Neuroligin-2 absence on wake/sleep architecture and electrocorticographic spectral and multifractal activities

Neuroligin-2 (NLGN2) regulates GABAergic neurotransmission and is linked to neurodevelopmental disorders. The absence of NLGN2 in male mice decreases time spent in slow wave sleep and alters electrocorticographic (ECoG) activity. We tested whether NLGN2 absence also impacts wake/sleep states in females and whether sleep phenotypes associate with specific omic signatures of the cerebral cortex. Nlgn2 knockout (KO) mice and wild-type (WT) littermates were implanted with ECoG electrodes, and ECoG signals were recorded for 48 hours. Other cohorts were submitted to motor cortex sampling followed by quantifications of the transcriptome or proteome. KO mice of both sexes spent less time in slow wave and paradoxical sleep, and KO males (but not females) showed more wake and slow wave sleep episodes during the light period. Mutant animals of both sexes showed widespread differences in wake/sleep ECoG spectral activity when compared to WT mice, including a slower theta peak frequency during paradoxical sleep. The most prominent Hurst exponent was significantly increased in Nlgn2 KO animals during all states, and Hurst exponents were less dispersed during paradoxical sleep only in KO females. Less than 31% of genes with expression changed in KO versus WT mice were shared between females and males (e.g., linked to MAPK/ERK pathway, protein regulation and neurotransmission), and it was less than 15% in the case of proteins (e.g., related to calcium signaling and excitatory synapse function). Moreover, KO males showed a higher number (> 2.5 fold) of genes with expression significantly increased and decreased compared to control mice than KO females, but only KO females presented significantly lower levels of a subset of core proteins regulating synapses (e.g., SYNGAP1, HOMER1). The findings indicate that effects of NLGN2 absence on wake/sleep phenotypes and omic landscapes depend on biological sex, and could help understanding the origin of sleep disturbances in neurodevelopmental disorders.

neuroscience↗

bioRxiv2024

Electrocorticographic and Astrocytic Signatures of Stearoyl-CoA Desaturase Inhibition in the Triple Transgenic Mouse Model of Alzheimer's Disease

The symptomatology of Alzheimers disease (AD) includes cognitive deficits and sleep disturbances. Recent findings suggest the involvement of dysfunctions in lipid metabolism, such as oleic acid build-up, in the brain of AD patients and animal models. In addition, the inhibition of stearoyl-CoA desaturase (SCD), a lipid-converting enzyme, was shown to restore memory in triple transgenic (3xTg)-AD mice. In the brain, astrocytes regulate the synthesis of specific lipids. Alterations in astrocytes and their function were reported in AD patients and animal models, and astrocytes have been implicated in the regulation of sleep. However, the relationship between sleep disturbances, astrocytes and lipid metabolism remains to be explored in AD. This project thus aimed at assessing whether the inhibition of SCD restores sleep in 3xTg-AD mice, and whether this associated with modifications in astrocytic function. Wild-type (WT) and 3xTg-AD female mice (4-months old) received intracerebroventricular infusion of a SCD inhibitor (SCDi) or vehicle for 28 days, and a 24-hour electrocorticographic (ECoG) recording was conducted post-treatment. Post-mortem brain slices were stained for the astrocytic markers glial fibrillary acidic protein (GFAP) and 10-formyltetrahydrofolate dehydrogenase (ALDH1L1) to perform cell counting and/or morphological evaluation in the hippocampus, lateral hypothalamus and thalamus. The results indicate that the reduced time spent awake and increased time spent in slow wave sleep (SWS) in 3xTg-AD mice was not restored by the SCDi treatment. Similar observations were made concerning the increased number of wake and SWS bouts in 3xTg-AD mice. Rhythmic and scale-free ECoG activity were markedly altered in 3xTg-AD mice for all wake/sleep states, and SCDi significantly altered these phenotypes in a different manner in mutant mice in comparison to WT mice. GFAP- and ALDH1L1-positive cell densities were elevated in the hippocampus and lateral hypothalamus/thalamus of 3x-Tg-AD mice, respectively, and SCDi rescued the increase in the CA1 region in particular. Overall, these findings suggest that the multiple wake/sleep alterations in 3xTg-AD mice are not substantially restored by targeting lipid metabolism using SCD inhibition, at least for the targeted age window, but that this treatment can revert hippocampal changes in astrocytes. This work will benefit the understanding of the pathophysiology related to AD and associated sleep disturbances.

neuroscience↗

bioRxiv2022

Cortical miR-709 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.e., in early adulthood using conditional Dicer knockout (cKO) mice and in adult mice using an inducible conditional Dicer cKO (icKO) line. In both models, electroencephalographic (EEG) activity was affected and the response to sleep deprivation (SD), altered; while rapid-eye-movement sleep (REMS) rebound was compromised in both, EEG delta (1-4 Hz) power during non-REM sleep (NREMS) was reduced in cKO mice and increased in icKO mice. We subsequently investigated the effects of SD on the miRNA transcriptome and found that the expression of 48 forebrain miRNAs was affected, in particular, the activity-dependent miRNA miR-709. In vivo inhibition of miR-709 in the brain increased EEG power during NREMS in the slow-delta (0.75-1.75 Hz) range, particularly after periods of prolonged wakefulness. Transcriptome analysis of primary cortical neurons in vitro revealed that miR-709 regulates endosomal trafficking and glutamatergic receptor activity. A subset of the genes involved in glutamatergic transmission was affected also in the cortices of sleep-deprived, miR-709-inhibited mice. Our data implicate miRNAs in the regulation of EEG activity and indicate that miR-709 links neuronal excitability during wakefulness to brain synchrony during sleep, likely through the regulation of endosomal trafficking and glutamatergic signaling. Significance StatementMicroRNAs (miRNAs) are key regulators of gene expression playing vital roles both in postnatal brain development and its functioning in adult organisms. Here, we highlight a fundamental role for miRNAs in shaping EEG slow waves, which reflect synchronous neuronal firing, characteristic of NREM sleep (NREMS) in the adult murine cortex. Disruption of the miRNA-biogenesis machinery affected brain synchrony differently, depending on when it occurred during development. Moreover, sleep deprivation altered the expression of several miRNAs in a brain-region specific manner. Among those, we identified miR-709 to affect the expression of genes involved in endosomal-trafficking and glutamatergic-transmission, thereby linking neuronal activity during wakefulness to slow EEG waves during subsequent sleep. The current study causally implicates this specific miRNA and the molecular pathways it targets in modifying the generation of NREMS EEG slow waves, which are important in synaptic plasticity and brain functioning.

neuroscience↗

bioRxiv2019

Reassessing the validity of slow-wave dynamics as a proxy for NREM sleep homeostasis

Sleep-wake driven changes in NREM sleep (NREMS) EEG delta ({delta}: [~]0.75-4.5Hz) power are widely used as proxy for a sleep homeostatic process. We noted frequency increases in {delta}-waves in sleep-deprived (SD) mice, prompting us to re-evaluate how slow-wave characteristics relate to prior sleep-wake history. We discovered two types of {delta}-waves; one responding to SD with high initial power and fast, discontinuous decay ({delta}2: [~]2.5-3.5Hz) and another unrelated to time-spent-awake with slow, linear decays ({delta}1: [~]0.75-1.75Hz). Human experiments confirmed this {delta}-band heterogeneity. Similar to SD, silencing of centromedial thalamus neurons boosted {delta}2-waves, specifically. {delta}2-dynamics paralleled that of temperature, muscle tone, heart-rate, and neuronal UP/DOWN state lengths, all reverting to characteristic NREMS levels within the first recovery hour. Thus, prolonged waking seems to necessitate a physiological recalibration before typical NREMS can be reinstated. These short-lasting {delta}2-dynamics challenge accepted models of sleep regulation and function based on the merged {delta}-band as sleep-need proxy.

neuroscience↗

bioRxiv2019

Fxr1 regulates sleep and synaptic homeostasis

The fragile X autosomal homolog 1 (Fxr1) has been GWAS-associated to schizophrenia and insomnia but its contributions to brain functions are unclear. Homeostatic regulation of synaptic strength is essential for the maintenance of brain functions and engages both global and cell autonomous level processes. We used Crispr/Cas9-mediated somatic knockouts, overexpression, neuronal activity recordings and translatome sequencing, to examine the contribution of Fxr1 to cell-autonomous homeostatic synaptic scaling and global-level sleep homeostasis. Our findings indicate that Fxr1 is downregulated during scaling and sleep deprivation via a Gsk3{beta} dependent mechanism. In both conditions, downregulation of Fxr1 is essential for the homeostatic modulation of synaptic strength. Furthermore, overexpression of Fxr1 during sleep deprivation results in altered EEG signatures and reverts changes of translatome profiles. These findings indicate that Fxr1 represents a shared signaling hub linking cell autonomous homeostatic plasticity and system level sleep homeostasis with potential implications for neuropsychiatric illnesses.

neuroscience↗