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Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):28-37. doi: 10.1016/j.resp.2008.04.014.

Neurochemical and physiological correlates of a critical period of respiratory development in the rat.

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  • 1Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.


Despite its vital importance to life, respiration is not mature at birth in mammals, but rather, it undergoes a great deal of growth, refinement, and adjustments postnatally. Many adjustments do not follow smooth paths, but assume abrupt changes during certain postnatal periods that may render the animal less capable of responding to respiratory stressors. The present review focuses on neurochemical and physiological correlates of a critical period of respiratory development in the rat. In addition to an imbalanced expression of reduced excitatory and enhanced inhibitory neurotransmitters, a switch in the expressions of gamma-aminobutyric acid (GABA)A receptor subunits from alpha3 to alpha1 occurs around postnatal day (P)12 in the pre-Bötzinger nucleus and the ventrolateral subnucleus of the solitary tract nucleus. Possible subunit switches in a number of other neurotransmitter receptors are discussed. These neurochemical changes are paralleled by ventilatory adjustments at the end of the second postnatal week. At P13 and under normoxia, respiratory frequency reaches its peak before assuming a gradual fall, and both tidal volume and minute ventilation exhibit a significant rise prior to a plateau or a gradual decline until P21. The response to acute hypoxia is markedly reduced between P12 and P16, being lowest at P13. Thus, the end of the second postnatal week can be considered as a critical period of respiratory development, during which multiple neurochemical and physiological adjustments and switches are orchestrated at the same time, rendering the system extremely dynamic but, at the same time, vulnerable to externally imposed perturbations and insults. The critical period embodies a time of multi-system, multifaceted growth and adjustments. It is a plastic, transitional period that is also a part of the normal development of the respiratory system.

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