Much like locomotion or micturition, respiration is a rhythmic and stereotyped motor pattern controlled mainly by non-cortical
structures including a complex circuit in the brainstem. Because tight regulation of lung ventilation is essential from the beginning of life,
it has been presumed that the neural system regulating breathing is fixed, following a genetically predetermined developmental pattern.
Here, we review evidence indicating that early life exposure to a non-systemic stress in the form of neonatal maternal separation (NMS)
is sufficient to exert sex-specific consequences on the developmental trajectory of this vital homeostatic system that persist well into full
maturity. At adulthood, male rats subjected to NMS are hypertensive and show an abnormally high hypoxic chemoreflex that correlates
positively with respiratory instability during sleep. The effects are not observed in females. Investigation of the mechanisms this respiratory
phenotype have highlighted the importance of 1) neuroendocrine influences on respiratory regulation and 2) stress-related imbalance
between inhibitory (GABAergic) and excitatory (glutamatergic) modulation of the neural elements regulating breathing. These results
provide new and valuable insight into the origins of respiratory disorders related to neural control dysfunction such as sleep disordered
Keywords: Control of breathing, plasticity, development, neonatal stress, chemoreflex, sexual dimorphism.
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