Different neuronal populations of the rat median preoptic nucleus express c-fos during sleep and in response to hypertonic saline or angiotensin-II.

The median preoptic nucleus (MnPN) of the hypothalamus contains sleep-active neurones, and sleep-related Fos-immunoreactivity (IR) in this nucleus is primarily expressed in GABAergic cells. The MnPN also contains cells responsive to hypertonic saline and to angiotensin-II (Ang-II). To clarify functional relationships between MnPN neurones involved in the regulation of sleep and body fluid homeostasis, we examined c-fos expression in the MnPN after administration of hypertonic saline and Ang-II in both spontaneously sleeping and sleep-deprived rats. Systemic administration of hypertonic saline and intracerebroventricular (i.c.v.) injection of Ang-II increased Fos-IR in both spontaneously sleeping and sleep-deprived rats, compared to control animals. To determine if the population of MnPN neurones activated in response to osmotic and hormonal stimuli is similar to or different from neurones activated during sleep, we quantified Fos-IR in MnPN GABAergic neurones in spontaneously sleeping hypertonic saline- and Ang-II-treated rats versus respective control rats. Fos-IR evoked by these treatments occurred primarily (80-85%) in non-GABAergic neurones. Findings of the present study provide evidence that separate populations of MnPN neurones are involved in the regulation of sleep and body fluid homeostasis.

Persistence of sleep-temperature coupling after suprachiasmatic nuclei lesions in rats.

The suprachiasmatic nucleus (SCN) regulates the circadian rhythms of body temperature (T(b)) and vigilance states in mammals. We studied rats in which circadian rhythmicity was abolished after SCN lesions (SCNx rats) to investigate the association between the ultradian rhythms of sleep-wake states and brain temperature (T(br)), which are exposed after lesions. Ultradian rhythms of T(br) (mean period: 3.6 h) and sleep were closely associated in SCNx rats. Within each ultradian cycle, nonrapid eye movement (NREM) sleep was initiated 5 +/- 1 min after T(br) peaks, after which temperature continued a slow decline (0.02 +/- 0.006 degrees C/min) until it reached a minimum. Sleep and slow wave activity (SWA), an index of sleep intensity, were associated with declining temperature. Cross-correlation analysis revealed that the rhythm of T(br) preceded that of SWA by 2-10 min. We also investigated the thermoregulatory and sleep-wake responses of SCNx rats and controls to mild ambient cooling (18 degrees C) and warming (30 degrees C) over 24-h periods. SCNx rats and controls responded similarly to changes in ambient temperature. Cooling decreased REM sleep and increased wake. Warming increased T(br), blunted the amplitude of ultradian T(br) rhythms, and increased the number of transitions into NREM sleep. SCNx rats and controls had similar percentages of NREM sleep, REM sleep, and wake, as well as the same average T(b) within each 24-h period. Our results suggest that, in rats, the SCN modulates the timing but not the amount of sleep or the homeostatic control of sleep-wake states or T(b) during deviations in ambient temperature.

Interleukin 1beta enhances non-rapid eye movement sleep and increases c-Fos protein expression in the median preoptic nucleus of the hypothalamus.

Interleukin 1beta (IL-1) is a key mediator of the acute phase response in an infected host and acts centrally to coordinate responses to an immune challenge, such as fever and increased non-rapid eye movement (NREM) sleep. The preoptic area (POA) is a primary sleep regulatory center in the brain: the ventrolateral POA (VLPO) and median preoptic nucleus (MnPN) each contain high numbers of c-Fos protein immunoreactive (IR) neurons after sleep but not after waking. We hypothesized that IL-1 mediates increased NREM sleep through activation of these sleep-active sites. Rats injected intracerebroventricularly with IL-1 (10 ng) at dark onset spent significantly more time in NREM sleep 4-5 h after injection. This increase in NREM sleep was associated with increased numbers of Fos-IR neurons in the MnPN, but not in the VLPO. Fos IR in the rostral MnPN was significantly increased 2 h post IL-1 injection, although the percentage of NREM sleep in the preceding 2 h was the same as controls. Fos IR was also increased in the extended VLPO 2 h postinjection. Finally, Fos IR in the MnPN did not differ significantly between IL-1 and vehicle-treated rats that had been sleep deprived for 2 h postinjection, but it was increased in VLPO core. Taken together, these results suggest that Fos IR in the MnPN after IL-1 is not independent of behavioral state and may require some threshold amount of sleep for its expression. Our results support a hypothesis that IL-1 enhances NREM sleep, in part, through activation of neurons in the MnPN of the hypothalamus.