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

Abstract

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 GABA A receptor subunits from α3 to α1 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.

Developmental nicotine exposure adversely effects respiratory patterning in the barbiturate anesthetized neonatal rat

“…This age range encompasses both preterm and very early post-natal periods of the human infant. Although the risk for respiratory instability and SIDS is predicted to peak at P12-13, corresponding to the "critical period" in rat brainstem development (Liu et al, 2006;Liu and Wong-Riley, 2010;Wong-Riley and Liu, 2008), the present findings serve as proof of concept and demonstrate the potential to apply ACF in detection of respiratory disturbances at the very earliest development stages.…”

Younger rats are more susceptible to the lethal effects of sarin than adult rats: 24 h LC50for whole-body (10 and 60 min) exposures

“…The end of the second postnatal week is a critical period for respiratory development in rats due to a drastic imbalance in the expression of excitatory and inhibitory neurotransmitters, a switch in the expression of GABA A receptor subunits and a sudden drop in cytochrome oxidase activity in several brain stem respiratory nuclei at PND 12 (Wong-Riley & Liu, 2008). These neurochemical changes are closely followed by significant increases in ventilation (Liu et al, 2006) and metabolic rate (Liu et al, 2009) at PND 13, which require too much energy to maintain under hypoxic conditions.…”

Intermittent hypercapnia enhances CO2 responsiveness and overcomes serotonergic dysfunction

“…Protocols were designed to administer cycles of mild hypercapnia to pups, without altering maternal conditions and while limiting maternal separation. This developmental period was chosen to follow the apparent critical period proximal to P12 where rat chemosensitivity is altered (Putnam et al, 2005; Wong-Riley and Liu, 2005, 2008), and the developmental period beyond which chemosensitive 5-HT neurons have been identified in vitro (Wang and Richerson, 1999; Wu, 2008). Prior attempts to influence hypercapnic responsiveness showed no influence when a comparable IHc protocol was conducted between P7 and P14 (Steggerda et al, 2009).…”