Respiratory rhythm and pattern generation in the neonatal rat

Episodic breathing, or periodic breathing, is a hallmark respiratory pattern in mammalian neonates that can be observed in most species perinatally but transitions rapidly to continuous breathing after birth and is rarely expressed again in most mammals. The mechanisms producing this pattern remain unknown. My thesis focuses on two neonatal rat (Rattus norvegicus) preparations in which the episodic breathing pattern is expressed: in vivo and in vitro. I first examine breathing variability and occurrence of episodic breathing in vivo in two different strains of laboratory rat at two different temperatures during the early neonatal period to determine 1) How breathing variability transitions from highly irregular at birth to regular, continuous breathing seen in adults, and 2) whether episodic breathing occurs in the intact neonate, and if so, whether its expression differs based on age and body temperature. I observed a sharp decline in breathing variability and an increase in breathing frequency in both strains at both temperatures between P0 and P1. I was also able to observe episodic breathing only on the day of birth, and Sprague-Dawley rats displayed episodic breathing more frequently than Long Evans rats – indicating a potential strain-specific difference. Using the in vitro brainstem-spinal cord preparation of the neonatal rat, I examined the role of the inhibitory neurotransmitter GABA and the pons in the occurrence of episodic breathing during the first few days of life, in an attempt to narrow down the mechanistic basis for the episodic breathing pattern. I found that fictive breathing frequency, burst amplitude, and the frequency of episodic breaths were not influenced by the constitutive presence of GABA in the brainstem, but the presence of the pons, and not GABA, was the main variable influencing the incidence of episodic breathing. Removal of the pons drastically decreased episodicity irrespective of GABA presence. My data indicate that the likely mechanism controlling the expression of the episodic breathing pattern originates in the pons rather than the medulla, and that GABA does not play a significant role in this expression. Collectively, my data suggest that a more complex process controls the expression of episodic breathing in vitro.