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Mongrain, V.

Publications and source records attributed to Mongrain, V..

2 recordsLinked to original sources

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

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