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The Journal of Neuroscience, April 5, 2006, 26(14):3721-3730; doi:10.1523/JNEUROSCI.0026-06.2006

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Behavioral/Systems/Cognitive
Modulation of Respiratory Rhythmogenesis by Chloride-Mediated Conductances during the Perinatal Period

Jun Ren and John J. Greer

Department of Physiology, Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada T6G 2S2

Correspondence should be address to Dr. John J. Greer, University of Alberta, Department of Physiology, 513 Heritage Medical Research Centre, Edmonton, Alberta, Canada T6G 2S2. Email: john.greer{at}ualberta.ca

Respiratory rhythmogenesis is modulated by chloride-mediated conductances via GABA_A and glycine receptors. In this study, we determine the actions of chloride-mediated conductances on respiratory rhythmogenesis in perinatal rats from the time of inception of fetal inspiratory drive through to the newborn period. Data were obtained from perinatal rat models, including (1) recordings of nerve roots and neuronal population discharge from medullary slice and brainstem–spinal cord in vitro preparations, (2) gramicidin perforated-patch recordings of respiratory neurons in medullary slices, and (3) plethysmographic recordings from unanesthetized pups. The transition from excitatory to inhibitory effects on respiratory rhythmogenesis occurs at approximately embryonic day 19. By birth, GABA, glycine, and taurine all induce a hyperpolarization of the membrane potential in respiratory medullary neurons and a suppression of respiratory frequency. The age-dependant change in the actions of chloride-mediated conductances is regulated by the development of chloride cotransporters (KCC2 and NKCC1). The function of KCC2 chloride cotransporter is strongly modulated by [K⁺]_o, which must be considered when evaluating responses observed using in vitro perinatal preparations.

Key words: GABAergic modulation; glycine; medulla; respiration; neonatal; prenatal; taurine

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Received Jan. 4, 2006; revised Feb. 15, 2006; accepted Feb. 17, 2006.

Correspondence should be address to Dr. John J. Greer, University of Alberta, Department of Physiology, 513 Heritage Medical Research Centre, Edmonton, Alberta, Canada T6G 2S2. Email: john.greer{at}ualberta.ca

This article has been cited by other articles:

				C. A. Del Negro, K. Kam, J. A. Hayes, and J. L. Feldman Asymmetric control of inspiratory and expiratory phases by excitability in the respiratory network of neonatal mice in vitro J. Physiol., March 15, 2009; 587(6): 1217 - 1231. [Abstract] [Full Text] [PDF]

				M. Thoby-Brisson and J. J. Greer Anatomical and functional development of the pre-Botzinger complex in prenatal rodents J Appl Physiol, April 1, 2008; 104(4): 1213 - 1219. [Abstract] [Full Text] [PDF]

				J. Ren and J. J. Greer Neurosteroid modulation of respiratory rhythm in rats during the perinatal period J. Physiol., July 15, 2006; 574(2): 535 - 546. [Abstract] [Full Text] [PDF]

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