A video polysomnographic study of spontaneous smiling during sleep in newborns.

The objective of the present study was to confirm the link between spontaneous smiling and active sleep in newborns, and to identify the role of the cortex in the generation of spontaneous smiles. A total of 12 healthy newborns born at term and three infants with major congenital abnormalities (two with hydranencephaly and one with a left hemispherectomy) were evaluated by video and polysomnography during a 3-hr sleep period. Smiles were graded and their association with isolated rapid eye movements and grouped rapid eye movements was analysed. In all, 383 smiles were recorded of which 377 occurred during active sleep. Smiles were shown to be significantly associated with active sleep (p < .0001) and with grouped rapid eye movements (p < .0001). Bilateral smiles were more frequent than asymmetrical smiles. Among asymmetrical smiles, left-sided smiles were more frequent than right-sided smiles (p < .0001). Maternal stimulation during active sleep did not increase smiles. Smiling was absent during active sleep only in the infant with total hydranencephaly in whom nearly all cortical tissue was absent. In conclusion, smiling occurs in healthy newborns, almost exclusively in active sleep and is associated with grouped rapid eye movements. In infants with major congenital abnormalities, smiling is abolished only when nearly all of the cerebral cortex is absent. These results support the hypothesis of the role of active sleep in the stimulation of neuronal circuits responsible for spontaneous smiling and emphasise the importance of cortical areas in newborn smiling.

d-Serine diffusion through the blood-brain barrier: effect on d-serine compartmentalization and storage.

d-Serine is a co-agonist of N-methyl-d-aspartate (NMDA) receptors. It has been implicated in the etiology of schizophrenia and has shown efficacy as an adjuvant to reduce positive and negative symptoms of schizophrenia. In addition, d-serine can modulate cognition in animals when administered alone. However, the neurochemical effects of exogenous d-serine on extra- and intra-cellular d-serine brain levels are poorly understood. In this study, we used both high performance liquid chromatography (HPLC) and enzyme-based microelectrode biosensors to quantify d-serine in the rat brain. We demonstrated levels of 2.3-2.8µM in the extracellular medium, 4µM in plasma and 188pmol/mg in brain tissue samples. An intraperitoneal (i.p.) d-serine injection (1g/kg) produced a slow increase in extracellular d-serine concentration in the cortex despite a surge in d-serine up to 13mM in the plasma, indicating poor diffusion through the blood-brain barrier. Using the respective volume fractions of blood, extracellular and intracellular spaces published in the literature, we estimated that d-serine intracellular stores represented more than 99% of total d-serine. These intracellular stores almost doubled 3h after d-serine administration. Overall, our data indicate that d-serine administration increases brain extra- and intra-cellular concentrations despite weak diffusion through the blood-brain barrier. These results pave the way for a better understanding of the neurochemical mechanisms by which d-serine administration modulates cognition.

Acute administration of the novel serotonin and noradrenaline reuptake inhibitor, S33005, markedly modifies sleep-wake cycle architecture in the rat.

RATIONALE: The interrelationship between depressive states and sleep-wake cycle architecture is characterised by a decreased latency to the first paradoxical sleep (PS) episode, together with an enhancement of PS during the first part of the night. Conversely, slow-wave sleep (SWS) is decreased and intermittent awakenings increased. Notably, antidepressant treatment is generally associated with a diminution of PS. OBJECTIVES: In light of these observations, we examined the influence of acute administration of the novel mixed serotonin-noradrenaline reuptake blocker, (-)1-(1-dimethylaminomethyl 5-methoxybenzocyclobutan-1-yl)-cyclohexanol HCl (S33005), upon sleep-wake architecture in rats. METHODS: Animals were injected with vehicle or incremental doses of S33005 at the onset of either the dark or light periods. Digitised polygraphic recordings were performed, and changes evoked by S33005 were determined over 24-h recording periods, i.e., number and duration of sleep-wake episodes, latencies to PS and SWS, power band spectra of the electroencephalogram (EEG) and circadian changes. RESULTS: At 0.04 mg/kg, S33005 was inactive, whereas at 0.63 mg/kg, it modestly increased PS latencies and diminished PS duration during the light period. At 10 mg/kg, S33005 reduced markedly PS duration for about 4-h when injected prior to both light and dark periods. Latency to PS was prolonged, and the circadian acrophase was delayed. These effects are in keeping with previous studies of monoamine reuptake inhibitors, but, notably, SWS duration was increased when S33005 was injected at the onset of the light phase (+4%). These changes occurred without marked modifications in circadian rhythmicity or EEG spectral band power. Finally, even at the highest dose of S33005, only a limited rebound of SWS (+5%) and PS (+10%) was apparent. Amongst antidepressant to date examined, this is an original profile of influence upon sleep patterns. CONCLUSIONS: These results demonstrate a pattern of influence of S33005 upon sleep-wake architecture in rats which is globally consistent with antidepressant properties, but with a distinctive enhancement of restorative slow-wave sleep.

Chloramphenicol decreases brain glucose utilization and modifies the sleep-wake cycle architecture in rats.

We studied the effects of chloramphenicol on brain glucose utilization and sleep-wake cycles in rat. After slightly anaesthetized animals were injected with [18F]fluoro-2-deoxy-D-glucose, we acquired time-concentration curves from three radiosensitive beta microprobes inserted into the right and left frontal cortices and the cerebellum, and applied a three-compartment model to calculate the cerebral metabolic rates for glucose. The sleep-wake cycle architecture was analysed in anaesthetic-free rats by recording electroencephalographic and electromyographic signals. Although chloramphenicol is a well-established inhibitor of oxidative phosphorylation, no compensatory increase in glucose utilization was detected in frontal cortex. Instead, chloramphenicol induced a significant 23% decrease in the regional cerebral metabolic rate for glucose. Such a metabolic response indicates a potential mismatch between energy supply and neuronal activity induced by chloramphenicol administration. Regarding sleep-wake states, chloramphenicol treatment was followed by a 64% increase in waking, a 20% decrease in slow-wave sleep, and a marked 59% loss in paradoxical sleep. Spectral analysis of the electroencephalogram indicates that chloramphenicol induces long-lasting modifications of delta-band power during slow-wave sleep.