MATURATIONAL CHANGES IN THE RESPIRATORY RHYTHM GENERATOR OF THE MOUSE

The changes in motor activity of the respiratory rhythm generator were quantitatively analysed in mice (from birth to at least 56 days old) in both awake and anaesthetized preparations, as well as in vitro to define the age at which the respiratory network is mature. In awake and anaesthetized spontaneously breathing mice respiratory-related thoracic movements were recorded and revealed an age-dependent increase in both inspiratory time (45 %) and cycle length (22 %) over the first 15 days of life. Similarly, the pattern of phrenic nerve activity recorded from anesthetized animals also changed from a short, rapid onset and offset burst, without a post-inspiratory phase (0-10 days old), to a discharge of longer duration which included both ramp and post-inspiratory components (> 15 days). This pattern was comparable to that seen in adult mice (> 56 days old). A recently developed tilted-sagittal brainstem slice preparation containing an isolated, but functionally intact, medullary respiratory network was employed in our in vitro studies. Since this preparation generates respiratory rhythmic activity spontaneously in both neonatal and mature mice (> 56 days old) it has permitted a direct comparison of the respiratory motor output pattern, recorded from the hypoglossal (XII) motor nucleus, during post-natal development in similar preparations. Consistent with our in vivo findings there was an age-dependent change in the motor pattern. The rhythmic burst of XII neurones recorded from slices of neonates (0-10 days old) was short in duration and decremented whereas a longer discharge (increase of 625 % compared to neonate) containing a plateau component was seen in animals more than 15 days old. In addition, the cycle length of rhythmic XII neurones increased (143 %) and, together with the changes in burst duration, reached a steady-state value over a similar time course to the maturational changes in phrenic nerve activity recorded in vivo. Our in vivo and in vitro data indicate that the central respiratory network of the mouse appears to be mature at post-natal day 15.