The rhythmic, transverse medullary slice preparation in respiratory neurobiology: Contributions and caveats

Our understanding of the sites and mechanisms underlying rhythmic breathing as well as the neuromodulatory control of respiratory rhythm, pattern, and respiratory motoneuron excitability during perinatal development has advanced significantly over the last 20 years. A major catalyst was the development in 1991 of the rhythmically-active medullary slice preparation, which provided precise mechanical and chemical control over the network as well as enhanced physical and optical access to key brainstem regions. Insights obtained in vitro have informed multiple mechanistic hypotheses. In vivo tests of these hypotheses, performed under conditions of reduced control and precision but more obvious physiological relevance, have clearly established the significance for respiratory neurobiology of the rhythmic slice preparation. We review the contributions of this preparation to current understanding/concepts in respiratory control, and outline the limitations of this approach in the context of studying rhythm and pattern generation, homeostatic control mechanisms and murine models of human genetic disorders that feature prominent breathing disturbances.

► We describe the rhythmic medullary slice preparation and variations of it. ► We review key contributions that have resulted from the analysis of this preparation. ► We outline key hypotheses generated in vitro that have led to critical tests in vivo. ► We discuss the main caveats and limitations affecting data interpretation.