MECHANISMS OF RESPIRATORY RHYTHM GENERATION CHANGE PROFOUNDLY DURING EARLY-LIFE IN MICE AND RATS

To study the ontogenesis of central respiratory rhythm generation, a novel brainstem slice preparation was developed that generates respiratory rhythmic activity spontaneously in mice and rats at all post-natal ages. The slice was made by tilting the brainstem to include both the ventrolateral and dorsomedial medulla. This 'tilted-sagittal' slice contained the nucleus ambiguus, the hypoglossal motor nucleus (XII) and the nucleus of the solitary tract which were preserved intact throughout their rostro-caudal extent. Using this rhythmic preparation it has been possible for the first time to directly compare the significance of glycinergic mechanisms for respiratory rhythmogenesis between newborns and mature rodents in vitro. Our findings demonstrate that during the first two weeks of life there are profound changes in both the motor pattern of rhythmic XII neurons and sensitivity of the respiratory rhythm to strychnine blockade of glycine receptors. Thus, developmental changes in strychnine-sensitive receptors are vital for the maturation of the respiratory network and it is suggested that any disturbance in their development may be lethal.