D-ꞵ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance.

The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood.

Effect of daridorexant on sleep architecture in patients with chronic insomnia disorder: a pooled post hoc analysis of two randomized phase 3 clinical studies.

Study Objectives: Post hoc analysis to evaluate the effect of daridorexant on sleep architecture in people with insomnia, focusing on features associated with hyperarousal.

Methods: We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg).

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.

TAAR1 agonist ulotaront modulates striatal and hippocampal glutamate function in a state-dependent manner.

Aberrant dopaminergic and glutamatergic function, particularly within the striatum and hippocampus, has repeatedly been associated with the pathophysiology of schizophrenia. Supported by preclinical and recent clinical data, trace amine-associated receptor 1 (TAAR1) agonism has emerged as a potential new treatment approach for schizophrenia. While current evidence implicates TAAR1-mediated regulation of dopaminergic tone as the primary circuit mechanism, little is known about the effects of TAAR1 agonists on the glutamatergic system and excitation-inhibition balance.

-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance.

The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood.

Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice.

Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep-wake disturbances. The nychthemeral sleep-wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light-dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light-dark alternations exert direct and acute influences on sleep and waking.

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).

Light therapy with boxes or glasses to counteract effects of acute sleep deprivation.

Sleep deprivation, in the context of shift work, is an increasing major public health issue. We aimed to determine whether early light administration can counteract sleep deprivation effects, and to compare LED-glasses with a traditional light therapy box. This cross-over design study included 18 individuals exposed to light therapy for 30 minutes at 5 am after one night of complete sleep deprivation, to mimic the night shift condition.

Sleep-wake-driven and circadian contributions to daily rhythms in gene expression and chromatin accessibility in the murine cortex.

The timing and duration of sleep results from the interaction between a homeostatic sleep-wake-driven process and a periodic circadian process, and involves changes in gene regulation and expression. Unraveling the contributions of both processes and their interaction to transcriptional and epigenomic regulatory dynamics requires sampling over time under conditions of unperturbed and perturbed sleep. We profiled mRNA expression and chromatin accessibility in the cerebral cortex of mice over a 3-d period, including a 6-h sleep deprivation (SD) on day 2.

Dynactin1 depletion leads to neuromuscular synapse instability and functional abnormalities.

Background: Dynactin subunit 1 is the largest subunit of the dynactin complex, an activator of the molecular motor protein complex dynein. Reduced levels of DCTN1 mRNA and protein have been found in sporadic amyotrophic lateral sclerosis (ALS) patients, and mutations have been associated with disease, but the role of this protein in disease pathogenesis is still unknown.

Methods: We characterized a Dynactin1a depletion model in the zebrafish embryo and combined in vivo molecular analysis of primary motor neuron development with live in vivo axonal transport assays in single cells to investigate ALS-related defects.

Cold-inducible RNA-binding protein (CIRBP) adjusts clock-gene expression and REM-sleep recovery following sleep deprivation.

Sleep depriving mice affects clock-gene expression, suggesting that these contribute to sleep homeostasis. The mechanisms linking extended wakefulness to clock-gene expression are, however, not well understood. We propose CIRBP to play a role because its rhythmic expression is i) sleep-wake driven and ii) necessary for high-amplitude clock-gene expression .

Rocking Promotes Sleep in Mice through Rhythmic Stimulation of the Vestibular System.

Rocking has long been known to promote sleep in infants and, more recently, also in adults, increasing NREM sleep stage N2 and enhancing EEG slow waves and spindles. Nevertheless, whether rocking also promotes sleep in other species, and what the underlying mechanisms are, has yet to be explored. In the current study, C57BL/6J mice equipped with EEG and EMG electrodes were rocked laterally during their main sleep period, i.

Hyperdopaminergism in lenticulostriate stroke-related restless legs syndrome: an imaging study.

Objective: The pathophysiology of restless legs syndrome (RLS) involves a dopaminergic dysregulation that remains poorly understood, with controversial data from the literature. Stroke-related RLS is a rare condition that involves primarily the basal ganglia, the paramedian pons, and the thalamus. Given these elements, we studied dopaminergic metabolism in patients with RLS secondary to lenticulostriate infarction using structural and nuclear imaging in the striatum ipsilateral to the infarction area, as compared to the contralateral side.

Fatigue in Rapsyn-Deficient Zebrafish Reflects Defective Transmitter Release.

Unlabelled: Rapsyn-deficient myasthenic syndrome is characterized by a weakness in voluntary muscle contraction, a direct consequence of greatly reduced synaptic responses that result from poorly clustered acetylcholine receptors. As with other myasthenic syndromes, the general muscle weakness is also accompanied by use-dependent fatigue. Here, we used paired motor neuron target muscle patch-clamp recordings from a rapsyn-deficient mutant line of zebrafish to explore for the first time the mechanisms causal to fatigue.

Intraspinal Sensory Neurons Provide Powerful Inhibition to Motor Circuits Ensuring Postural Control during Locomotion.

In the vertebrate spinal cord, cerebrospinal fluid-contacting neurons (CSF-cNs) are GABAergic neurons whose functions are only beginning to unfold. Recent evidence indicates that CSF-cNs detect local spinal bending and relay this mechanosensory feedback information to motor circuits, yet many CSF-cN targets remain unknown. Using optogenetics, patterned illumination, and in vivo electrophysiology, we show here that CSF-cNs provide somatic inhibition to fast motor neurons and excitatory sensory interneurons involved in the escape circuit.

Alerting or Somnogenic Light: Pick Your Color.

In mammals, light exerts pervasive effects on physiology and behavior in two ways: indirectly through clock synchronization and the phase adjustment of circadian rhythms, and directly through the promotion of alertness and sleep, respectively, in diurnal and nocturnal species. A recent report by Pilorz and colleagues describes an even more complex role for the acute effects of light. In mice, blue light acutely causes behavioral arousal, whereas green wavelengths promote sleep.

Optimization of a Neurotoxin to Investigate the Contribution of Excitatory Interneurons to Speed Modulation In Vivo.

Precise control of speed during locomotion is essential for adaptation of behavior in different environmental contexts [1-4]. A central question in locomotion lies in understanding which neural populations set locomotor frequency during slow and fast regimes. Tackling this question in vivo requires additional non-invasive tools to silence large populations of neurons during active locomotion.

Arvicanthis ansorgei, a Novel Model for the Study of Sleep and Waking in Diurnal Rodents.

Study Objectives: Sleep neurobiology studies use nocturnal species, mainly rats and mice. However, because their daily sleep/wake organization is inverted as compared to humans, a diurnal model for sleep studies is needed. To fill this gap, we phenotyped sleep and waking in Arvicanthis ansorgei, a diurnal rodent widely used for the study of circadian rhythms.

Synchronous and asynchronous modes of synaptic transmission utilize different calcium sources.

Asynchronous transmission plays a prominent role at certain synapses but lacks the mechanistic insights of its synchronous counterpart. The current view posits that triggering of asynchronous release during repetitive stimulation involves expansion of the same calcium domains underlying synchronous transmission. In this study, live imaging and paired patch clamp recording at the zebrafish neuromuscular synapse reveal contributions by spatially distinct calcium sources.

Serotonin transporter polymorphism is associated with increased apnea-hypopnea index in older adults.

Rationale: A functional polymorphism of the serotonin transporter gene (5-HTTLPR) has previously been related to upper airway pathology, but its contribution to obstructive sleep apnea (OSA), a highly prevalent sleep disorder in older adults, remains unclear.

Objectives: We aimed to investigate the relationship between apnea-hypopnea index (AHI) and genetic variations in the promoter region of the 5-HTTLPR in older adults.

Methods: DNA samples from 94 community-dwelling older adults (57% female, mean age 72 ± 8) were genotyped for the 5-HTTLPR polymorphism.

Zebrafish calls for reinterpretation for the roles of P/Q calcium channels in neuromuscular transmission.

A long-held tenet of neuromuscular transmission is that calcium-dependent neurotransmitter release is mediated by N-type calcium channels in frog but P/Q-type channels in mammals. The N-type assignment in frog is based principally on pharmacological sensitivity to ω-conotoxin GVIA. Our studies show that zebrafish neuromuscular transmission is also sensitive to ω-conotoxin GVIA.

Non-circadian direct effects of light on sleep and alertness: lessons from transgenic mouse models.

Light exerts a strong non-visual influence on human physiology and behavior. Additionally light is known to affect sleep indirectly through the phase shifting of circadian rhythms, and directly, promoting alertness in humans and sleep in nocturnal species. Little attention has been paid to the direct non-image-forming influence of light until recently with the discovery and emerging knowledge on melanopsin, a photopigment which is maximally sensitive to the blue spectrum of light and expressed in a subset of intrinsically photosensitive retinal ganglion cells.