Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A receptors.

Optochemistry, an emerging pharmacologic approach in which light is used to selectively activate or deactivate molecules, has the potential to alleviate symptoms, cure diseases, and improve quality of life while preventing uncontrolled drug effects. The development of in-vivo applications for optochemistry to render brain cells photoresponsive without relying on genetic engineering has been progressing slowly. The nucleus accumbens (NAc) is a region for the regulation of slow-wave sleep (SWS) through the integration of motivational stimuli.

Sleep-Deep-Learner is taught sleep-wake scoring by the end-user to complete each record in their style.

Sleep-wake scoring is a time-consuming, tedious but essential component of clinical and preclinical sleep research. Sleep scoring is even more laborious and challenging in rodents due to the smaller EEG amplitude differences between states and the rapid state transitions which necessitate scoring in shorter epochs. Although many automated rodent sleep scoring methods exist, they do not perform as well when scoring new datasets, especially those which involve changes in the EEG/EMG profile.

Sleep-Deep-Net learns sleep wake scoring from the end-user and completes each record in their style.

Sleep-wake scoring is a time-consuming, tedious but essential component of clinical and pre-clinical sleep research. Sleep scoring is even more laborious and challenging in rodents due to the smaller EEG amplitude differences between states and the rapid state transitions which necessitate scoring in shorter epochs. Although many automated rodent sleep scoring methods exist, they do not perform as well when scoring new data sets, especially those which involve changes in the EEG/EMG profile.

Circuits and components of delta wave regulation.

Sleep is vital and the deepest stages of sleep occur within Non-rapid-eye-movement sleep (NREM), defined by high electroencephalographic power in the delta (~0.5-4 Hz) wave frequency range. Delta waves are thought to facilitate a myriad of physical and mental health functions.

Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior.

The basal forebrain (BF) is involved in arousal, attention, and reward processing but the role of individual BF neuronal subtypes is still being uncovered. Glutamatergic neurons are the least well-understood of the three main BF neurotransmitter phenotypes. Here we analyzed the distribution, size, calcium-binding protein content and projections of the major group of BF glutamatergic neurons expressing the vesicular glutamate transporter subtype 2 (vGluT2) and tested the functional effect of activating them.

Basal Forebrain Parvalbumin Neurons Mediate Arousals from Sleep Induced by Hypercarbia or Auditory Stimuli.

The ability to rapidly arouse from sleep is important for survival. However, increased arousals in patients with sleep apnea and other disorders prevent restful sleep and contribute to cognitive, metabolic, and physiologic dysfunction [1, 2]. Little is currently known about which neural systems mediate these brief arousals, hindering the development of treatments that restore normal sleep.

Alterations in sleep, sleep spindle, and EEG power in mGluR5 knockout mice.

The type 5 metabotropic glutamate receptor (mGluR5) represents a novel therapeutic target for schizophrenia and other disorders. Schizophrenia is associated with progressive abnormalities in cortical oscillatory processes including reduced spindles (8-15 Hz) during sleep and increased delta (0.5-4 Hz)- and gamma-band activity (30-80 Hz) during wakefulness.

Thalamic Reticular Nucleus Parvalbumin Neurons Regulate Sleep Spindles and Electrophysiological Aspects of Schizophrenia in Mice.

The thalamic reticular nucleus (TRN) is implicated in schizophrenia pathology. However, it remains unclear whether alterations of TRN activity can account for abnormal electroencephalographic activity observed in patients, namely reduced spindles (10-15 Hz) during sleep and increased delta (0.5-4 Hz) and gamma-band activity (30-80 Hz) during wakefulness.

Validation of an automated sleep spindle detection method for mouse electroencephalography.

Study Objectives: Sleep spindles are abnormal in several neuropsychiatric conditions and have been implicated in associated cognitive symptoms. Accordingly, there is growing interest in elucidating the pathophysiology behind spindle abnormalities using rodent models of such disorders. However, whether sleep spindles can reliably be detected in mouse electroencephalography (EEG) is controversial necessitating careful validation of spindle detection and analysis techniques.

Activation of basal forebrain purinergic P2 receptors promotes wakefulness in mice.

The functions of purinergic P2 receptors (P2Rs) for extracellular adenosine triphosphate (ATP) are poorly understood. Here, for the first time, we show that activation of P2Rs in an important arousal region, the basal forebrain (BF), promotes wakefulness, whereas inhibition of P2Rs promotes sleep. Infusion of a non-hydrolysable P2R agonist, ATP-γ-S, into mouse BF increased wakefulness following sleep deprivation.

Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats.

Sleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well-known energy booster in cellular energy homeostasis.

The NLRP3 inflammasome modulates sleep and NREM sleep delta power induced by spontaneous wakefulness, sleep deprivation and lipopolysaccharide.

Both sleep loss and pathogens can enhance brain inflammation, sleep, and sleep intensity as indicated by electroencephalogram delta (δ) power. The pro-inflammatory cytokine interleukin-1 beta (IL-1β) is increased in the cortex after sleep deprivation (SD) and in response to the Gram-negative bacterial cell-wall component lipopolysaccharide (LPS), although the exact mechanisms governing these effects are unknown. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome protein complex forms in response to changes in the local environment and, in turn, activates caspase-1 to convert IL-1β into its active form.

The role of adenosine in the maturation of sleep homeostasis in rats.

Unlabelled: Sleep homeostasis in rats undergoes significant maturational changes during postweaning development, but the underlying mechanisms of this process are unknown. In the present study we tested the hypothesis that the maturation of sleep is related to the functional emergence of adenosine (AD) signaling in the brain. We assessed postweaning changes in 1) wake-related elevation of extracellular AD in the basal forebrain (BF) and adjacent lateral preoptic area (LPO), and 2) the responsiveness of median preoptic nucleus (MnPO) sleep-active cells to increasing homeostatic sleep drive.

Cholinergic Neurons in the Basal Forebrain Promote Wakefulness by Actions on Neighboring Non-Cholinergic Neurons: An Opto-Dialysis Study.

Unlabelled: Understanding the control of sleep-wake states by the basal forebrain (BF) poses a challenge due to the intermingled presence of cholinergic, GABAergic, and glutamatergic neurons. All three BF neuronal subtypes project to the cortex and are implicated in cortical arousal and sleep-wake control. Thus, nonspecific stimulation or inhibition studies do not reveal the roles of these different neuronal types.

Metabolic signals in sleep regulation: recent insights.

Sleep and energy balance are essential for health. The two processes act in concert to regulate central and peripheral homeostasis. During sleep, energy is conserved due to suspended activity, movement, and sensory responses, and is redirected to restore and replenish proteins and their assemblies into cellular structures.

Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations.

Cortical gamma band oscillations (GBO, 30-80 Hz, typically ∼40 Hz) are involved in higher cognitive functions such as feature binding, attention, and working memory. GBO abnormalities are a feature of several neuropsychiatric disorders associated with dysfunction of cortical fast-spiking interneurons containing the calcium-binding protein parvalbumin (PV). GBO vary according to the state of arousal, are modulated by attention, and are correlated with conscious awareness.

Cholinergic neurons of the basal forebrain mediate biochemical and electrophysiological mechanisms underlying sleep homeostasis.

The tight coordination of biochemical and electrophysiological mechanisms underlies the homeostatic sleep pressure (HSP) produced by sleep deprivation (SD). We have reported that during SD the levels of inducible nitric oxide synthase (iNOS), extracellular nitric oxide (NO), adenosine [AD]ex , lactate [Lac]ex and pyruvate [Pyr]ex increase in the basal forebrain (BF). However, it is not clear whether all of them contribute to HSP leading to increased electroencephalogram (EEG) delta activity during non-rapid eye movement (NREM) recovery sleep (RS) following SD.

Cholinergic neurons excite cortically projecting basal forebrain GABAergic neurons.

The basal forebrain (BF) plays an important role in the control of cortical activation and attention. Understanding the modulation of BF neuronal activity is a prerequisite to treat disorders of cortical activation involving BF dysfunction, such as Alzheimer's disease. Here we reveal the interaction between cholinergic neurons and cortically projecting BF GABAergic neurons using immunohistochemistry and whole-cell recordings in vitro.

Control of sleep and wakefulness.

This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex.

Decoupling of sleepiness from sleep time and intensity during chronic sleep restriction: evidence for a role of the adenosine system.

Study Objective: Sleep responses to chronic sleep restriction (CSR) might be very different from those observed after short-term total sleep deprivation. For example, after sleep restriction continues for several consecutive days, animals no longer express compensatory increases in daily sleep time and sleep intensity. However, it is unknown if these allostatic, or adaptive, sleep responses to CSR are paralleled by behavioral and neurochemical measures of sleepiness.

Knockdown of orexin type 1 receptor in rat locus coeruleus increases REM sleep during the dark period.

The locus coeruleus (LC) regulates sleep/wakefulness and is densely innervated by orexinergic neurons in the lateral hypothalamus. Here we used small interfering RNAs (siRNAs) to test the role of LC orexin type 1 receptor (OxR1) in sleep–wake control. In sleep studies, bilateral OxR1 siRNA injections led to an increase of time spent in rapid eye movement (REM) sleep, which was selective for the dark (active) period, peaked at approximately 30% of control during the second dark period after injection and then disappeared after 4 days.