Invited Review: Developmental plasticity in respiratory control

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Abstract
Development of the mammalian respiratory control system begins early in gestation and does not achieve mature form until weeks or months after birth. A relatively long gestation and period of postnatal maturation allows for prolonged pre- and postnatal interactions with the environment, including experiences such as episodic or chronic hypoxia, hyperoxia, and drug or toxin exposures. Developmental plasticity occurs when such experiences, during critical periods of maturation, result in long-term alterations in the structure or function of the respiratory control neural network. A critical period is a time window during development devoted to structural and/or functional shaping of the neural systems subserving respiratory control. Experience during the critical period can disrupt and alter developmental trajectory, whereas the same experience before or after has little or no effect. One of the clearest examples to date is blunting of the adult ventilatory response to acute hypoxia challenge by early postnatal hyperoxia exposure in the newborn. Developmental plasticity in neural respiratory control development can occur at multiple sites during formation of brain stem neuronal networks and chemoafferent pathways, at multiple times during development, by multiple mechanisms. Past concepts of respiratory control system maturation as rigidly predetermined by a genetic blueprint have now yielded to a different view in which extremely complex interactions between genes, transcriptional factors, growth factors, and other gene products shape the respiratory control system, and experience plays a key role in guiding normal respiratory control development. Early-life experiences may also lead to maladaptive changes in respiratory control. Pathological conditions as well as normal phenotypic diversity in mature respiratory control may have their roots, at least in part, in developmental plasticity.