Homeostatic coupling of cortical and brainstem delta rhythms in sleeping infant rats

ABSTRACT The emergence of the cortical delta rhythm (1-4 Hz) during quiet sleep (QS) is a major milestone in brain development. In rats, this milestone is achieved between 8 and 12 days of postnatal (P) age. We previously reported an age-dependent increase in PZ delta-rhythmic activity that is synchronized with cortical delta and entrained by breathing. Here, we ask whether this long-distance synchrony persists in response to perturbations to sleep homeostasis or respiration. First, using male and female P12 rats, we investigated the coupling strength between frontal cortex and PZ in response to a short but intense period of sleep deprivation. During recovery sleep, we observed a rebound in delta power in both PZ and cortex, even in the absence of increased QS duration, indicating that PZ and cortical delta power are equivalent markers of homeostatic sleep regulation. Analyses of phase-locking and lagged cross-correlation revealed persistent temporal coupling between the two rhythms such that cortical delta reliably lagged PZ delta regardless of changes in sleep pressure. Curiously, we also observed an increase in breathing depth during recovery sleep, which we confirmed in a separate cohort of pups. Next, using mild hypercapnia (5% CO 2 ) to alter breathing frequency and depth, we produced decreases in cortical and PZ delta power along with decreases in the depth of breathing. These findings provide additional support for the notion that PZ and cortical delta rhythms function as distantly interconnected components within a developmentally emerging sleep-homeostatic system that is also intimately tied with the brainstem respiratory network. SIGNIFICANCE STATEMENT We reported previously that the delta rhythm that defines slow-wave sleep is not confined to the forebrain but also occurs synchronously in the medulla. This study in infant rats uses two perturbations to assess the coupling strength of cortical and brainstem delta. Using sleep deprivation and hypercapnia, we show that delta power increases or decreases in lockstep in the two regions, respectively. Our results reinforce the notion that delta across these two regions is strongly coupled and adds a new dimension to our understanding of the interconnectedness of the delta rhythm and respiration.