Microinjection of glutamate into the pedunculopontine tegmentum induces REM sleep and wakefulness in the rat

The aim of this study was to test the hypothesis that the cells in the brain stem pedunculopontine tegmentum (PPT) are critically involved in the normal regulation of wakefulness and rapid eye movement (REM) sleep. To test this hypothesis, one of four different doses of the excitatory amino acid L-glutamate (15, 30, 60, and 90 ng) or saline (control vehicle) was microinjected unilaterally into the PPT while the effects on wakefulness and sleep were quantified in freely moving chronically instrumented rats. All microinjections were made during wakefulness and were followed by 6 h of polygraphic recording. Microinjection of 15- ng (0.08 nmol) and 30-ng (0.16 nmol) doses of L-glutamate into the PPT increased the total amount of REM sleep. Both doses of L-glutamate increased REM sleep at the expense of slow-wave sleep (SWS) but not wakefulness. Interestingly, the 60-ng (0.32 nmol) dose of L-glutamate increased both REM sleep and wakefulness. The total increase in REM sleep after the 60-ng dose of L-glutamate was significantly less than the increase from the 30-ng dose. The 90-ng (0.48 nmol) dose of L-glutamate kept animals awake for 2-3 h by eliminating both SWS and REM sleep. These results show that the L-glutamate microinjection into the PPT can increase wakefulness and/or REM sleep depending on the dosage. These findings support the hypothesis that excitation of the PPT cells is causal to the generation of wakefulness and REM sleep in the rat. In addition, the results of this study led to the identification of the PPT dosage of L-glutamate that optimally induces wakefulness and REM sleep. The knowledge of this optimal dose will be useful in future studies investigating the second messenger systems involved in the regulation of wakefulness and REM sleep.     

Effects of localized pontine lesions on auditory brain-stem evoked potentials and binaural processing in humans

Objectives and mehtods: Four sets of measurements were obtained from 11 patients (44–80 years old) with small, localized pontine lesions due to vascular disease: (1) Monaural auditory brain-stem evoked potentials (ABEPs; peaks I to VI); (2) Binaural ABEPs processed for their binaural interaction components (BICs) in the latency range of peaks IV to VI; (3) magnetic resonance imaging (MRI) of the brain-stem; and (4) psychoacoustics of interaural time disparity measures of binaural localization. ABEPs and BICs were analyzed for peak latencies and interpeak latency differences. Three-channel Lissajous' trajectories (3-CLTs) were derived for ABEPs and BICs and the latencies and orientations of the equivalent dipoles of ABEP and BICs were inferred from them.Results: Intercomponent latency measures of monaurally evoked ABEPs were abnormal in only 3 of the 11 patients. Consistent correlations between sites of lesion and neurophysiological abnormality were obtained in 9 of the 11 patients using 3-CLT measures of BICs. Six of the 11 patients had absence of one or more BIC components. Seven of the 11 had BICs orientation abnormality and 3 had latency abnormalities. Trapezoid body (TB) lesions (6 patients) were associated with an absent (two patients with ventral-caudal lesions) or abnormal (one patient with ventral-rostral lesions) dipole orientation of the first component (at the time of ABEPs IV), and sparing of this component with midline ventral TB lesions (two patients). A deviant orientation of the second BICs component (at the time of ABEPs V) was observed with ventral TB lesions. Psychoacoustic lateralization in these patients was biased toward the center. Rostral lateral lemniscus (LL) lesions (3 patients) were associated with absent (one patient) or abnormal (two patients) orientation of the third BICs component (at the time of ABEPs VI); and a side-biased lateralization with behavioral testing.Conclusions: These results indicate that: (1) the BICs component occurring at the time of ABEPs peak IV is dependent on ventral-caudal TB integrity; (2) the ventral TB contributes to the BICs component at the time of ABEPs peak V; and (3) the rostral LL is a contributing generator of the BICs component occurring at the time of ABEP peak VI.     

Effects of humid heat exposure in later sleep segments on sleep stages and body temperature in humans

This study sought to investigate the effects of humid heat exposure in later sleep segments on sleep stages and body temperature in humans. The subjects were eight healthy males, from whom informed consent had been obtained. The experiments were carried out under three different sets of conditions: a control climate [air temperature (Ta)=26°C, relative humidity (RH)=50%] (C); a humid heat climate (Ta=32°C, RH=80%) (H); and a humid heat exposure in later sleep segments (C for the first 3 h 45 min, followed by a 30-min transition to H, which was then maintained for the last 3 h 45 min) (C–H). Electroencephalogram, EOG, and mental electromyogram, rectal temperature (Tre), and skin temperature (Tsk) were continuously measured. The total amount of wakefulness was significantly increased in H compared to C–H or C. Compared to C, wakefulness in C–H and H was significantly increased during later sleep segments. Tre and mean Tsk were significantly higher in H than in C–H or C. In C–H, Tsk and Tre increased to levels equal to those observed in H after Ta and RH increase. Whole body sweat loss was significantly lower in C–H and C than in H. These results suggest that humid heat exposure in the later sleep segment reduces thermal load as compared to full-night humid heat exposure. In daily life, the use of air conditioning in the initial sleep hours can protect sleep and thermoregulation.     

Effects of head cooling on human sleep stages and body temperature

The purpose of this study was to confirm the effect of head cooling on human sleep stages and body temperature. Nine healthy male volunteers with a mean age of 25 +/- 3.77 years served as subjects. The experiments were carried out under three different sets of conditions: 26 degrees C, relative humidity (RH) 50% (26/50); 32 degrees C, RH 80% (32/80); and 32 degrees C RH 80% with the use of a cooling pillow (32/80 HC). The subjects slept from 2300 hours to 0700 hours with a cotton blanket, wearing short-sleeved pyjamas and shorts on a bed, which was covered with a sheet. Electroencephalograms, electro-ouclogram, and mental electromyelograms were recorded through the night. Rectal temperature (Tre) and skin temperature (Tsk) were measured continuously. Whole-body sweat and the tympanic temperature (Tty) were measured before and after sleep. Wakefulness significantly increased at 32/80 than at 26/50; however, no significant difference was observed between 32/80 HC and 26/50. Tre and mean Tsk were higher both at 32/80 and 32/80 HC than at 26/50. The whole-body sweat loss was significantly greater and Tty in the morning was higher at 32/80 than 32/80 HC and 26/50. These results suggest that head cooling during sleep may help to decrease the whole-body sweat rate during sleep under humid heat conditions.     

Effects of muscimol and flurazepam on the sleep EEG in the rat

In order to assess the possible role of GABA receptor function in the hypnotic property of benzodiazepines, we have examined the sleep EEG in rats given the GABA agonist muscimol, alone and in combination with flurazepam. Muscimol 0.05 and 0.1 mg/kg IP failed to alter sleep latency or total sleep time, and did not interact with the sleep-enhancing properties of flurazepam 20 mg/kg IP. These observations, in conjunction with a previous study of bicuculline, suggest that the hypnotic property of benzodiazepines may not be mediated by alteration of GABAergic activity.     

Effects of alternating 45-min light-dark cycles on sleep in the rat

We studied the effect of alternating 45-min light-dark (L-D) cycles on sleep in rats. Introduction of short L-D cycles did not abolish the normal circadian rhythm of sleep-wake activity. The amount of non-REM sleep was however increased in the L and decreased in the D 45-min periods. REM was promoted in the D and inhibited in the L 45-min periods. The influence of L-D or D-L transitions depended on the sleep wake activity immediately before the transition.     

Effects of chloramphenicol and thiamphenicol on sleep of the mouse]

The oral administration of 0.25-2.0 g/kg of chloramphenicol at 9h selectively suppresses paradoxical sleep in mice for a duration of 2-4 hours. A dose of 1 g/kg given at 17h suppresses paradoxical sleep for 7 hours. Slow wave sleep decreased for 2 hours after administration. Thiamphenicol (1 g/kg) has no effect under the same conditions.     

Long-delay learning in rats with parabrachial pontine lesions

Two experiments were conducted to test the hypothesis that ratswith lesions in the parabrachial nucleus of the pons (PbN) canacquire conditioned taste aversions only if the conditionedand unconditioned stimuli are presented close together in time.In experiment 1, rats with lesions in the medial PbN, lateralPbN or outside of the PbN (lesioned control), and unoperatedcontrol rats were trained to avoid Na-saccharin in a one-bottletest. In this procedure, a 5-min delay was imposed between the15-min Na-saccharin presentation and an injection of LiCl (0.3M, 1 % body weight, i.p.). Results showed that, after threeNa-saccharin-LiCl pairings, all rats, except the medial PbNgroup, acquired a strong aversion to Na-saccharin. In experiment2, the same rats were presented with LiCl (0.12 M) in their15-min daily access to fluid on 3 alternate days. Although ratsin the medial PbN group drank more LiCl on day 1 than rats inthe other groups, they significantly reduced their LiCl consumptionon day 2 and did not differ from other groups by day 3. Resultsare discussed in terms of possible behavioral and physiologicalmechanisms that might account for these phenomena.