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This Article Full Text Full Text (PDF) All Versions of this Article: 583/1/299    most recent jphysiol.2007.135160v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Genest, S.-E. Articles by Kinkead, R. Search for Related Content PubMed PubMed Citation Articles by Genest, S.-E. Articles by Kinkead, R. Related Collections Respiratory

¹ Pediatrics
² Neuroscience Research Units, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Université Laval, Québec, QC, Canada

Neonatal maternal separation (NMS) affects respiratory control development as adult male (but not female) rats previously subjected to NMS show a hypoxic ventilatory response 25% greater than controls. The paraventricular nucleus of the hypothalamus (PVN) is an important modulator of respiratory activity. In the present study, we hypothesized that in awake rats, altered GABAergic inhibition within the PVN contributes to the enhancement of hypoxic ventilatory response observed in rats previously subjected to NMS. During normoxia, the increase in minute ventilation following microinjection of bicuculline (1 mM) within the PVN is greater in NMS versus control rats. These data show that regulation of ventilatory activity related to tonic inhibition of the PVN is more important in NMS than control rats. Microinjection of GABA or muscimol (1 mM) attenuated the ventilatory response to hypoxia (12% O₂) in NMS rats only. The higher efficiency of microinjections in NMS rats is supported by results from GABA_A receptor autoradiography which revealed a 22% increase in GABA_A receptor binding sites within the PVN of NMS rats versus controls. Despite this increase, however, NMS rats still show a larger hypoxic ventilatory response than controls, suggesting that within the PVN the larger number of GABA_A receptors either compensate for (1) a deficient GABAergic modulation, (2) an increase in the efficacy of excitatory inputs converging onto this structure, or (3) both. Together, these results show that the life-long consequences of NMS are far reaching as they can compromise the development of vital homeostatic function in a way that may predispose to respiratory disorders.

(Received 23 April 2007; accepted after revision 6 June 2007; first published online 14 June 2007)
Corresponding author Richard Kinkead: Centre de Recherche (D0–711), Hôpital St-François d'Assise, 10 rue de l'Espinay, Québec, QC, Canada G1L 3L5. Email: richard.kinkead{at}crsfa.ulaval.ca

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