Drive latencies in hypoglossal motoneurons indicate developmental change in the brainstem respiratory network

The respiratory rhythm originates and diverges from the brainstem to drive thousands of motoneurons that are responsible for control of the diaphragm, intercostals and upper airway. These motoneurons are known to have a wide range of phase relationships, even within a single motoneuron pool. The proposed source of this rhythm, the preBötzinger complex (preBötC), responds to an array of developmental changes in the first days post-birth, specifically at postnatal day 3 (P3). We hypothesize that such developmental changes in the preBötC have a direct effect on motoneuron phase relationships and should be detectable around age P3. To test our hypothesis, we obtained single- and dual-voltage-clamp recordings of hypoglossal motoneurons in an in vitro slice preparation. We introduce a novel approach to analyzing the phase relationships between motoneurons by using cross-correlation analysis to determine the drive latencies. This analysis reveals that the distribution of drive latencies undergoes a significant change at or before age P3. We use a computational model of the in vitro slice to demonstrate the observed phase differences and hypothesize that network heterogeneity alone may not be sufficient to explain them. Through simulations, we show the effects on the preBötC of different network characteristics such as clustering and common inputs.