“Cortical Delta” in the Medulla of Sleeping Infant Rats

Abstract

SummaryIn early development when sleep is the most prevalent behavioral state, active (REM) sleep is preeminent before it is supplanted by quiet (non-REM) sleep. In rats, the developmental increase in quiet sleep is accompanied by the sudden emergence of the cortical delta rhythm (0.5-4 Hz) around postnatal day (P) 12. We sought to explain the emergence of cortical delta by assessing developmental changes in the activity of the parafacial zone (PZ), a medullary structure thought to regulate quiet sleep in adults. We recorded from PZ and predicted an age-related increase in neural activity during increasing periods of delta-rich cortical activity. Instead, we discovered a state-dependent pattern of neural activity comprising rhythmic bursts—separated by periods of complete silence—that are phase-locked to a local delta rhythm. Moreover, PZ and cortical delta were coherent at P12, but not at P10. PZ delta was also phase-locked to respiration, suggesting that reported links between respiration and cortical delta are traceable to sleep-dependent modulation of PZ activity by respiratory pacemakers in the ventral medulla. Disconnecting the main olfactory bulbs from the cortex did not diminish cortical delta, indicating that the influence of respiration on delta at this age is not mediated indirectly through nasal breathing. Finally, we observed increasing expression of parvalbumin-expressing terminals in PZ across these ages, supporting a role for GABAergic inhibition in PZ’s rhythmicity. The discovery of delta-rhythmic neural activity in the medulla—at the moment of cortical delta’s developmental emergence—opens a new path to understanding the brainstem’s role in regulating quiet sleep.