Neurons of the cholinergic mesopontine tegmentum preferentially discharge during REM sleep and are thought to promote this state. It has been hypothesized they are inhibited during wakefulness by serotonergic input. The present study used the microdialysis sampling procedure coupled to microbore HPLC to measure extracellular serotonin levels in the pedunculopontine tegmental nucleus (PPT) in naturally sleeping cats. Extracellular serotonin levels were found to be highest during periods of wakefulness, lower during slow wave sleep, and lowest during periods of REM sleep. During wakefulness serotonin levels (mean ± SEM) measured in 10 µl samples were 1.14 ± 0.13 fmol/sample, whereas during slow wave sleep levels declined significantly to 72% of the wakefulness baseline (0.85 ± 0.11 fmol/sample), and dropped further to 45% of the wakefulness baseline in REM samples (0.52 ± 0.10 fmol/sample; all p's<0.003). The decrease in PPT serotonin levels during sleep may be an important determinant in the timing of REM sleep cyclicity. The data support the hypothesis that, during slow wave sleep and REM sleep, the declining levels of serotonin release the PPT REM-promoting neurons from serotonergic inhibition, which, in turn, leads to increases in acetylcholine release in terminal areas, facilitating the emergence of REM sleep.

Sleep Research Online

Narcolepsy-Cataplexy (NC) is a neurological disorder associated with the human leukocyte antigen HLA DR2. This is a prerequisite for the disease in 95 to 98% of Caucasian patients. It has been demonstrated that the HLA DQB1*0602 allele is a better marker for narcolepsy than DRB1*1501 (DR2). We present a DR-negative and DQB1*0602-positive Caucasian Spanish patient with a very unusual genotype. A 20-year-old male presented with a 12-year history of excessive daytime sleepiness and sudden muscle weakness caused by laughter and disturbed nocturnal sleep. He had never presented hypnagogic hallucinations or sleep paralysis. The family history was negative. Physical and neurological examinations were normal. The Epworth Sleepiness Scale score was 21/24, The Ullanlinna Scale score was 20/40. The polysomnographic recording showed short sleep latency, increased percentage of stage 1 (St 1), increased number of body movements and decreased sleep efficiency index. MSLT data: mean sleep latency of 1 minute and three sleep onset rapid eye movement (REM) periods (SOREMPs). HLA phenotype: A1, A11; Cw5, Cw7; B44, B39; Bw4, Bw6; DR4, DR8; DR53; DQ6, DQ8 and at the gene level: DRB1*0402, DQB1*0302; DRB1*0806, DQB1*0602. The DRB1*0806 and DQB1*0602 genotype is very infrequent in NC and identical to one African-American case in the series by Mignot et al. (1997a), and to a Caucasian case in another series by Mignot et al. (1997b). This indicates the genetic heterogeneity of the NC.

Sleep Research Online

Blood adenosine metabolism, including metabolites and metabolizing enzymes, was studied during the sleep period in human volunteers. Searching for significant correlations among biochemical parameters found: adenosine with state 1 of slow-wave sleep (SWS); activity of 5'-nucleotidase with state 2 of SWS; inosine and AMP with state 3-4 of SWS; and activity of 5'-nucleotidase and lactate with REM sleep. The correlations were detected in all of the subjects that presented normal hypnograms, but not in those who had fragmented sleep the night of the experiment. The data demonstrate that it is possible to obtain information of complex brain operations such as sleep by measuring biochemical parameters in blood. The results strengthen the notion of a role played by adenosine, its metabolites and metabolizing enzymes, during each of the stages that constitute the sleep process in humans.

Sleep Research Online

The present work is the first in a series of studies designed to examine the role of a brainstem GABAergic system in the control of the behavioral states of sleep and wakefulness. GABA, muscimol (a GABA_A receptor agonist) and bicuculline methiodide (a GABA_A receptor antagonist) were microinjected, separately, into the nucleus pontis oralis (NPO) in three chronic, unanesthetized cats. The effects of these microinjections on the behavioral states of sleep and wakefulness were then examined. The injection of either GABA or muscimol induced wakefulness; quiet sleep and active sleep were suppressed. In contrast, the injection of bicucculline induced a prolonged state that was similar to naturally-occurring active sleep. These findings indicate the existence of GABAergic processes capable of controlling the activity of neurons within the NPO that are involved in the control of sleep and waking states. Specifically, these data suggest that cells within the NPO must be tonically inhibited by a GABAergic brainstem system in order for the state of wakefulness to be generated and maintained.

Sleep Research Online

The experiments were conducted on 24 adult male Wistar rats to find out the alterations in the levels of monoamines and dendritic spine densities in the medial preoptic area and cortex after total sleep deprivation. Noradrenaline was reduced in the medial preoptic area, though there was no significant change in the cortex. Dopamine and serotonin were decreased both in the medial preoptic area and in the cortex. Dendritic spine counts in the medial preoptic area and the motor cortex were increased after total sleep deprivation. Enhanced release of the monoamines and their subsequent breakdown during sleep deprivation could be responsible for the decreased levels of the transmitters. An increase in synaptic activity, resulting in the enhanced release of the transmitters, might be responsible for the increased spine density after total sleep deprivation. Localized changes in noradrenaline levels at the medial preoptic area suggest its involvement in sleep genesis and maintenance, though its possible contribution to other functions like thermoregulation and reproduction cannot be ruled out. As the available literature does not indicate a role for serotonin and dopamine at the medial preoptic area in sleep regulation, these changes may represent their participation in non-sleep functions.

Sleep Research Online