Developmental plasticity in the neural control of breathing

The respiratory control system undergoes a diversity of morphological and physiological transformational stages during intrauterine development as it prepares to transition into an air-breathing lifestyle. Following birth, the respiratory system continues to develop and may pass through critical periods of heightened vulnerability to acute environmental stressors. Over a similar time course, however, the developing respiratory control system exhibits substantial capacity to undergo plasticity in response to chronic or repeated environmental stimuli. A hallmark of developmental plasticity is that it requires an interaction between a stimulus (e.g., hypoxia, hyperoxia, or psychosocial stress) and a unique window of development; the same stimulus experienced beyond the boundaries of this critical window of plasticity (e.g., at maturity), therefore, will have little if any appreciable effect on the phenotype. However, there are major gaps in our understanding of the mechanistic basis of developmental plasticity. Filling these gaps in our knowledge may be crucial to advancing our understanding of the developmental origin of adult health and disease. In this review, we: i) begin by clarifying some ambiguities in the definitions of plasticity and related terms that have arisen in recent years; ii) describe various levels of the respiratory control system where plasticity can (or has been identified to) occur; iii) emphasize the importance of understanding the mechanistic basis of developmental plasticity; iv) consider factors that influence whether developmental plasticity is permanent or whether function can be restored; v) discuss genetic and sex-based variation in the expression of developmental plasticity; and vi) provide a translational perspective to developmental plasticity.