Cholinergic basal forebrain structures are involved in the mediation of the arousal effect of noradrenaline.

Cholinergic basal forebrain structures are implicated in cortical arousal and regulation of the sleep-wake cycle. Cholinergic neurones are innervated by noradrenergic terminals, noradrenaline excites them via alpha-1 receptors and microinjection of noradrenaline into the basal forebrain enhances wakefulness. However, it is not known to what extent the cholinergic versus non-cholinergic basal forebrain projection neurones contribute to the arousing effects of noradrenaline.

Effect of sleep deprivation on multi-unit discharge activity of basal forebrain.

The basal forebrain (BF) is an important wakefulness/arousal-promoting structure involved in homeostatic responses to sleep deprivation (SD). However, the effects of SD and subsequent sleep recovery on the BF discharge have not been investigated. Multi-unit BF activity was recorded on freely moving rats during 8 h of baseline (BL) and, on the following day, during 4 h of SD by gentle handling followed by 4 h of recovery.

Nitric oxide modulates the discharge rate of basal forebrain neurones: a study in freely moving rats.

In urethane-anaesthetized rats the infusion of a nitric oxide (NO)-donor [NOC-18, 1 mM (DETA/NO); 2,2'-(hydroxynitrosohydrazino)bis-ethanamine)] into the basal forebrain (BF) inhibited the discharge rate of most neurones, suggesting that NO may promote sleep via inhibition of wake-promoting neurones in the BF. However, this hypothesis still needs to be confirmed in freely moving rats. The objective of this study was to examine whether NO modulates the discharge rate of BF neurones in freely moving rats in a similar manner to anaesthetized rats.

Nitric oxide modulates the discharge rate of basal forebrain neurons.

Rationale: During prolonged wakefulness, the concentrations of nitric oxide (NO) and adenosine (AD) increase in the basal forebrain (BF). AD inhibits neuronal activity via adenosine (A1) receptors, thus providing a potential mechanism for sleep facilitation. Although NO in the BF increases adenosine and promotes sleep, it is not clear whether the sleep promotion by NO is mediated through adenosine increase, or NO independently of adenosine could modulate sleep.

Preliminary findings of proton magnetic resonance spectroscopy in occipital cortex during sleep deprivation.

Proton magnetic resonance spectroscopy ((1)H MRS) has revealed biochemical alterations in various psychiatric disorders. Changes in brain metabolites may be caused not only by the disease's progression or response to treatment, but also by physiological variability. The aim of this study was to use (1)H MRS to assess the effects of specific short-term physiological states on major metabolites.

Adenosine A1 receptor-dependent G-protein activity in the rat brain during prolonged wakefulness.

Adenosine accumulates in the basal forebrain during prolonged wakefulness and induces sleep. There is abundant evidence showing that the sleep-inducing effects are mediated locally in the basal forebrain through the adenosine A1 receptor. In previous studies an increase in the mRNA expression but no apparent change in the ligand binding of the A1 receptors have been found.

Stimulus-induced brain lactate: effects of aging and prolonged wakefulness.

Both aging and sleep deprivation disturb the functions of the frontal lobes. Deficits in brain energy metabolism have been reported in these conditions. Neurons use not only glucose but also lactate as their energy substrate.

The effect of age on prepro-orexin gene expression and contents of orexin A and B in the rat brain.

Orexin A and B (hypocretin 1 and 2) are hypothalamic peptides, which are synthesized in the lateral hypothalamus. Orexins participate in the regulation energy balance, food intake, vigilance and several endocrine and autonomic functions. The widespread projections of the orexin neurons suggest that they may have a role in coordination of different brain activities.

Nitrobenzylthioinosine (NBMPR) binding and nucleoside transporter ENT1 mRNA expression after prolonged wakefulness and recovery sleep in the cortex and basal forebrain of rat.

We have previously shown that extracellular adenosine levels increase locally in the basal forebrain (BF) during prolonged wakefulness, yet the cellular mechanisms of this local accumulation have remained unknown. The extracellular adenosine levels are strictly regulated by adenosine metabolism and its transport through cell membrane by the nucleoside transporters. As we previously showed that the key adenosine metabolizing enzymes were not affected by prolonged wakefulness, we now focussed on potential changes in the nucleoside transporters.

Sleep and its homeostatic regulation in mice lacking the adenosine A1 receptor.

Sleep deprivation (SD) increases extracellular adenosine levels in the basal forebrain, and pharmacological manipulations that increase extracellular adenosine in the same area promote sleep. As pharmacological evidence indicates that the effect is mediated through adenosine A1 receptors (A1R), we expected A1R knockout (KO) mice to have reduced rebound sleep after SD. Male homozygous A1R KO mice, wild-type (WT) mice, and heterozygotes (HET) from a mixed 129/C57BL background were implanted during anesthesia with electrodes for electroencephalography (EEG) and electromyography (EMG).

Adenosine, energy metabolism, and sleep.

While the exact function of sleep remains unknown, it is evident that sleep was developed early in phylogenesis and represents an ancient and vital strategy for survival. Several pieces of evidence suggest that the function of sleep is associated with energy metabolism, saving of energy, and replenishment of energy stores. Prolonged wakefulness induces signs of energy depletion in the brain, while experimentally induced, local energy depletion induces increase in sleep, similarly as would a period of prolonged wakefulness.

Metabolic imaging of human cognition: an fMRI/1H-MRS study of brain lactate response to silent word generation.

Proton magnetic resonance spectroscopy (1H-MRS) allows in vivo assessment of the metabolism related to human brain functions. Visual, auditory, tactile, and motor stimuli induce a temporary increase in the brain lactate level, which may act as a rapid source of energy for the activated neurons. The authors studied the metabolism of the frontal lobes during cognitive stimulation and measured local lactate levels with standard 1H-MRS, after localizing the activated area by functional MRI.

Sleep among habitually violent offenders with antisocial personality disorder.

The aim of the present study was to characterize the subjective and objective sleep and sleep quality in habitually violent offenders with DSM-IV diagnosis of antisocial personality disorder using a sleep questionnaire, actigraphy, polysomnography and power spectral analysis. Subjects for the study were 19 drug-free males (mean age +/- SEM 30.7 +/- 2.

Local energy depletion in the basal forebrain increases sleep.

Sleep saves energy, but can brain energy depletion induce sleep? We used 2,4-dinitrophenol (DNP), a molecule which prevents the synthesis of ATP, to induce local energy depletion in the basal forebrain of rats. Three-hour DNP infusions induced elevations in extracellular concentrations of lactate, pyruvate and adenosine, as well as increases in non-REM sleep during the following night. Sleep was not affected when DNP was administered to adjacent brain areas, although the metabolic changes were similar.

Adenosine kinase and 5'-nucleotidase activity after prolonged wakefulness in the cortex and the basal forebrain of rat.

The effect of prolonged wakefulness on adenosine kinase (AK), ecto-5'-nucleotidase and endo-5'-nucleotidase activity was assessed in the present study. Rats were sleep deprived for 3 or 6h, and one group was allowed to sleep 2h of recovery sleep after the 6h deprivation. The cortex and the basal forebrain were dissected, and frozen rapidly on dry ice.

Adenosine and sleep.

Adenosine is directly linked to the energy metabolism of cells. In the central nervous system an increase in neuronal activity enhances energy consumption as well as extracellular adenosine concentrations. In most brain areas high extracellular adenosine concentrations, through A(1) adenosine receptors, decrease neuronal activity and thus the need for energy.