Emergence and maturation of the respiratory oscillator during embryonic development

37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, SA207

Research Symposium: Emergence and maturation of the respiratory oscillator during embryonic development

M. Thoby-Brisson1

1. INCIA, CNRS, Univ Bordeaux2, Bordeaux, France.

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Breathing is a rhythmic motor act generated and controlled by hindbrain neuronal networks. An essential component of this generator is the pre-Bötzinger oscillator that produces and paces inspiration. In order to ensure survival at birth, the respiratory generator must be anatomically and functionally established during the prenatal period. Indeed, respiratory-like movements that play an important role in the proper maturation of the lungs, respiratory motoneurons and muscles, are already present during the ultimate stages of fetal development. Over the last decade we have sought insights into the mechanisms underlying the emergence and maturation of respiratory function during embryonic development, mainly by using electrophysiological and optical recordings of neuronal activities from reduced in vitro preparations from the mouse embryo, together with anatomical investigations. Here, I will first present some of the earlier work that has enabled 1), determining the time of inception of pre-Bötzinger circuit operation during embryonic development, 2), defining several genetic components required for the proper specification of the constitutive neuronal elements, and 3), describing some of the network properties expressed by the embryonic pre-Bötzinger oscillator. For example, we have found 1), that rhythmically organized, respiratory-related activity emerges at embryonic day 15 (E15) in the mouse (gestation lasting 18 to 19 days), 2), the homeobox gene Dbx1 is required for the specification of glutamatergic interneurons involved in respiratory rhythmogenesis, 3), intra-network synchronization relies upon glutamatergic synapses, and 4), some of the major neuronal membrane properties found at postnatal stages, including pacemaker properties, are already present before birth. Furthermore, because respiratory-related rhythmic activity is first detectable at the beginning of the last third of gestation (E15), and since important changes have been proposed to occur elsewhere in the CNS between E15 and birth, we are currently exploring the maturational processes that the pre-Bötzinger complex undergoes during this terminal prenatal period. In this context, I will present recent preliminary data on the functional maturation of the respiratory network associated with changes both in inhibitory synaptic signaling the properties of the population of respiratory neurons exhibiting pacemaker properties. In a translational perspective, finally, developmental anomalies in central respiratory neural control contribute significantly to human newborn mortality. Therefore, elucidating the cellular, molecular and genetic mechanisms involved in the formation and function of the respiratory generator during mammalian prenatal development is of particular importance to improving the understanding of pathologies and potentially to a better adaptation of therapeutical approaches to treating young babies suffering from respiratory distress.



Where applicable, experiments conform with Society ethical requirements.

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