DEVELOPMENT OF SLEEP HOMEOSTASIS IN THE DEVELOPING RAT

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DESCRIPTION (Adapted from applicant's abstract): This proposal will investigate the development of homeostatic sleep mechanisms and emergence of distinct arousal states in the neonatal rat. Arousal states cannot be identified by EEG parameters early in postnatal development, thus, arousal states in neonates are defined behaviorally as active sleep (AS) and quiet sleep (QS). AS and QS are generally considered homologous to REM and NREM sleep in adults, however, we found that EEG slow wave activity (SWA) occurs as often during AS as it does in QS at postnatal day 12 (P12). Thus, AS may not be an immature form of adult REM sleep, rather, it may be an undifferentiated state of the nervous system out of which NREM sleep emerges first and REM sleep second. We will test this hypothesis by determining when additional physiological parameters (e.g., respiratory patterns, electro-oculogram (EOG), brain and skin temperatures, and myoclonia) coalesce and form identifiable arousal states. We have developed a system for simultaneous recording of EEG, EMG, and behavioral sleep (by videotape) in neonatal rats continuously from P12 to P30. We found that adult-like responses to sleep deprivation (SD) were not present until P24; prior to that age, SD elicits increases in total sleep time (TST) without affecting the intensity or amount of SWA. From P12-P24, SWA increases progressively beyond adult levels, yet is not affected by SD. Thus, critical components of adult sleep homeostatic mechanisms must be absent prior to P24. Convergent lines of evidence support a role for adenosine in regulating SWA; however, its link to homeostatic mechanisms is unknown. We found that the adenosine A~ receptor agonist, N6-Cyclopentyladenosine (CPA), mimics the effects of SD in both adult and neonatal rats. Furthermore, CPA elicits SWA at ages (P16 and P20) when 3 h of SD have no effect on SWA. Thus, A1 receptors are present and functional but apparently not activated by SD. This proposal will investigate arousal state emergence, development of sleep homeostasis, and adenosinergic regulation of sleep homeostasis in neonatal rats. These studies will contribute significantly toward clinical studies on sudden infant death syndrome (SIDS) because they investigate the mechanisms by which arousal and, hence, failure to arouse, from sleep develop.