Brainstem and hypothalamic regulation of sleep pressure and rebound in newborn rats.

Abstract

Sleep pressure and rebound comprise the two compensatory or "homeostatic" responses to sleep deprivation. Although sleep pressure is expressed by infant rats as early as postnatal day (P)5, sleep rebound does not appear to emerge until after P11. Here we reexamine the developmental expression of these sleep-regulatory processes in P2 and P8 rats by depriving them of sleep for 30 min using a cold, arousing stimulus delivered to a cold-sensitive region of the snout. This method effectively increased sleep pressure over the 30-min period, defined as increases in the number of arousing stimuli presented over time. Moreover, sleep rebound, defined as increased sleep during the recovery period, is demonstrated here for the first time at these ages. Next, we show that precollicular transections in P2 rats prevent sleep rebound without affecting sleep pressure, thus suggesting that the brainstem is sufficient to support sleep pressure, but sleep rebound depends upon neural mechanisms that lie rostral to the transection. Finally, again in P2 rats, we used c-fos immunohistochemistry to examine neural activation throughout the neuraxis during sleep deprivation and recovery. Sleep deprivation and rebound were accompanied by significant increases in neural activation in both brainstem and hypothalamic nuclei, including the ventrolateral preoptic area and median preoptic nucleus. This early developmental expression of sleep pressure and rebound and the apparent involvement of brainstem and hypothalamic structures in their expression further solidifies the notion that sleep-wake processes in newborns -defined at these ages without reference to statedependent EEG activity -provide the foundation upon which the more familiar processes of adults are built.

Maturation of sleep homeostasis in developing rats: a role for preoptic area neurons

“…Increases in c-Fos ϩ cell counts have been reported in the MnPN and VLPO of P2 rats during recovery sleep following SD (47). This is in contrast to our failure to detect sleeprelated c-Fos expression in the VLPO of P22 rats.…”

“…Hence, quiet (NREM) and active (REM) sleep states were not differentiated in P2 rats. Todd et al (47) hypothesized that compensatory increases in sleep bout durations in P2 rats reflected an active sleep rebound and an increase in active sleep bout duration. What we report here are increases in average NREM sleep bout duration following SD on P30 and the absence of such an increase on P22 rats.…”

“…Increased sleep continuity in response to acute total SD has recently been reported in P2 rats (47). In that study, post-SD recovery sleep continuity was assessed from the mean duration of sleep episodes estimated from EMG recordings.…”

“…postnatal development; sleep-promoting systems; sleep homeostasis; preoptic hypothalamus SLEEP IN ADULT MAMMALS is homeostatically regulated. Rats exhibit a gradual emergence of different components of sleep homeostasis during postnatal development (5,14,40,47). Some aspects of sleep homeostasis are present in rats on postnatal day (P) 2, when sleep deprivation (SD) increases sleep time during postdeprivation recovery sleep (47).…”

“…Rats exhibit a gradual emergence of different components of sleep homeostasis during postnatal development (5,14,40,47). Some aspects of sleep homeostasis are present in rats on postnatal day (P) 2, when sleep deprivation (SD) increases sleep time during postdeprivation recovery sleep (47). Postdeprivation increases in non-rapid-eye-movement (NREM) sleep delta (␦) power, a measure of the intensity of homeostatic response in adults (7), are observed in P24 rats but not in P20 rats (14).…”