Partial activation of SIK3 delays the onset of wakefulness and alleviates hypersomnia due to the lack of protein kinase A-phosphorylation site.

Study Objectives: Sleep/wakefulness is regulated by intracellular signaling pathways composed of protein kinases such as salt-inducible kinase 3 (Sik3). Sik3-deficiency in neurons decreases NREM sleep time and electroencephalogram (EEG) delta power during NREM sleep, while Sik3Slp mice lacking a protein kinase A (PKA)-phosphorylation site, S551, show hypersomnia phenotype. In this study, we examined how a phosphomimetic mutation of the 221st threonine residue (T221E), which provides a partial (weak) constitutive activity of the kinase, affects sleep/wakefulness and circadian behavior.

Sleep-dependent memory consolidation in young and aged brains.

Young children and aged individuals are more prone to memory loss than young adults. One probable reason is insufficient sleep-dependent memory consolidation. Sleep timing and sleep-stage duration differ between children and aged individuals compared to adults.

An inherited life-threatening arrhythmia model established by screening randomly mutagenized mice.

Inherited arrhythmia syndromes (IASs) can cause life-threatening arrhythmias and are responsible for a significant proportion of sudden cardiac deaths (SCDs). Despite progress in the development of devices to prevent SCDs, the precise molecular mechanisms that induce detrimental arrhythmias remain to be fully investigated, and more effective therapies are desirable. In the present study, we screened a large-scale randomly mutagenized mouse library by electrocardiography to establish a disease model of IASs and consequently found one pedigree that exhibited spontaneous ventricular arrhythmias (VAs) followed by SCD within 1 y after birth.

Activation of lateral preoptic neurons is associated with nest-building in male mice.

Nest-building behavior is a widely observed innate behavior. A nest provides animals with a secure environment for parenting, sleep, feeding, reproduction, and temperature maintenance. Since animal infants spend their time in a nest, nest-building behavior has been generally studied as parental behaviors, and the medial preoptic area (MPOA) neurons are known to be involved in parental nest-building.

Neuronal subtype-specific transcriptomic changes in the cerebral neocortex associated with sleep pressure.

Sleep is homeostatically regulated by sleep pressure, which increases during wakefulness and dissipates during sleep. Recent studies have suggested that the cerebral neocortex, a six-layered structure composed of various layer- and projection-specific neuronal subtypes, is involved in the representation of sleep pressure governed by transcriptional regulation. Here, we examined the transcriptomic changes in neuronal subtypes in the neocortex upon increased sleep pressure using single-nucleus RNA sequencing datasets and predicted the putative intracellular and intercellular molecules involved in transcriptome alterations.