To establish a natural model of sleep-disordered breathing, we investigated respiration during wakefulness and sleep in the English bulldog. This breed is characterized by an abnormal upper airway anatomy, with enlargement of the soft palate and narrowing of the oropharynx. During sleep, the animals had disordered respiration and episodes of O2 desaturation. These were worst in rapid-eye-movement (REM) sleep, with most bulldogs having O2 saturations of less than 90% for prolonged durations. In contrast, control dogs never desaturated. In REM sleep, the bulldogs had episodes of both central and obstructive apnea, the latter being associated with paradoxical movements of the rib cage and abdomen. During wakefulness, the bulldogs were hypersomnolent as evidenced by a shortened sleep latency (mean of 12 min compared with greater than 150 min for controls). This animal model should facilitate studies of the natural history of the sleep apnea syndrome and its complications.

No abstract

No abstract

Psychological stressors have a prominent effect on sleep in general, and rapid eye movement (REM) sleep in particular. Disruptions in sleep are a prominent feature, and potentially even the hallmark, of posttraumatic stress disorder (PTSD) (Ross, R.J., Ball, W.A., Sullivan, K., Caroff, S., 1989. Sleep disturbance as the hallmark of posttraumatic stress disorder. American Journal of Psychiatry 146, 697-707). Animal models are critical in understanding both the causes and potential treatments of psychiatric disorders. The current review describes a number of studies that have focused on the impact of stress on sleep in rodent models. The studies are also in Table 1, summarizing the effects of stress in 4-h blocks in both the light and dark phases. Although mild stress procedures have sometimes produced increases in REM sleep, more intense stressors appear to model the human condition by leading to disruptions in sleep, particularly REM sleep. We also discuss work conducted by our group and others looking at conditioning as a factor in the temporal extension of stress-related sleep disruptions. Finally, we attempt to describe the probable neural mechanisms of the sleep disruptions. A complete understanding of the neural correlates of stress-induced sleep alterations may lead to novel treatments for a variety of debilitating sleep disorders.

The nucleus reticularis pontis oralis (RPO) and nucleus reticularis pontis caudalis (RPC) are implicated in the generation of rapid eye movement sleep (REM). Work in cats has indicated that GABA in RPO plays a role in the regulation of REM. We assessed REM after local microinjections into RPO and RPC of the gamma-aminobutyric acid-A (GABA(A)) agonist, muscimol (MUS), and the GABA(A) antagonist, bicuculline (BIC). Rats (90-day-old male Sprague-Dawley) were implanted with electrodes for recording electroencephalographs (EEG) and electromyographs (EMG). Guide cannulae were aimed into RPO (n = 9) and RPC (n = 8) for microinjecting MUS (200, 1,000.0 microM) and BIC (0.056, 0.333, 1.0, 1,000.0, and 10,000.0 microM). Animals received bilateral microinjections of saline, MUS, and BIC (0.2 microl microinjected at 0.1 microl/min) into each region followed by 6-h sleep recordings. In RPO, MUS (1,000.0 microM) suppressed REM and BIC (1,000.0 microM) enhanced REM. In RPC, MUS (200, 1,000.0 microM) suppressed REM, but BIC (1,000.0 microM and less) did not significantly affect REM. Higher concentrations of BIC (10,000.0 microM) injected into RPO (n = 9) and RPC (n = 4) produced wakefulness and escape behavior. The results indicate that GABA in RPO/RPC is involved in the regulation of REM and suggest site-specific differences in this regulation.

No abstract

No abstract

Serotonin [5-hydroxytryptamine (5-HT)] is believed to play an important inhibitory role in the regulation of rapid-eyemovement (REM) sleep. 5-HT may exert this effect on neurons of the laterodorsal tegmental (LDT) nuclei that are implicated as important in the generation of REM sleep and phasic REM events such as ponto-geniculo-occipital (PGO) waves and respiratory variability. In rat brainstem in vitro, 5-HT hyperpolarizes and inhibits the bursting properties of LDT neurons assumed to be involved in generating REM sleep and PGO waves. This study tests the hypothesis that in vivo 5-HT at the LDT nuclei suppresses REM sleep and phasic REM events. Ten rats were implanted with bilateral cannulae aimed at the LDT and with electrodes for recording the electroencephalogram, neck electromyogram, PGO waves, and diaphragm electromyogram. During REM sleep, 5-HT (100 nl; 1-1.5 mM), saline, or sham microinjections were performed; repeated microinjections were separated by ϳ1 hr. After the first microinjection, REM sleep as a percent of the total sleep time was reduced with 5-HT (mean percent REM, 19.9 Ϯ 2.5% for 5-HT vs 26.8 Ϯ 2.4% for saline; p ϭ 0.02). REM duration was reduced by 37% with 5-HT ( p ϭ 0.01), but REM episode frequency was changed less consistently ( p ϭ 0.21), suggesting that 5-HT mainly disrupted REM sleep maintenance. Per unit time of REM sleep, 5-HT had no effect on the amount or variability of REM PGO activity ( p Ͼ 0.740) or on the mean or coefficient of variation of REM respiratory rate ( p Ͼ 0.11). With subsequent microinjections, the effects of 5-HT on REM sleep were similar. A dose-dependent REM sleep suppression with 5-HT was observed in five rats tested. These data suggest that in vivo 5-HT at the LDT nuclei suppresses REM sleep expression. Although 5-HT did not disproportionately reduce the occurrence of phasic events within REM, total REM phasic activity was reduced because of less REM sleep after 5-HT. Key words: rapid-eye-movement sleep; brainstem; pons; serotonin; ponto-geniculo-occipital waves; laterodorsal tegmental nucleus; control of breathing; diaphragmThe cholinergic laterodorsal tegmental (LDT) and pedunculopontine tegmental (PP T) nuclei are believed to play a major role in generating rapid-eye-movement (REM) sleep and phasic REM events such as ponto-geniculo-occipital (PGO) waves (Steriade and McC arley, 1990;Jones, 1991;McC arley et al., 1995). Some LDT and PP T neurons show tonic increases in firing during REM, whereas others fire in bursts immediately preceding PGO waves (McC arley et al., 1978;Sakai and Jouvet, 1980;El Mansari et al., 1989;Steriade et al., 1990b;Kayama et al., 1992). This overall firing pattern contrasts with serotonergic dorsal raphe neurons (DRN) that project to the LDT and PP T (Honda and Semba, 1994) and fire minimally in REM (McGinty and Harper, 1976;Trulson and Jacobs, 1979; C espuglio et al., 1981). It has been proposed that serotonin [5-hydroxytryptamine (5-HT)] released from DRN suppresses LDT and PP T activity and hence REM sleep and PGO waves (McC arle...