Skip to main content

Volume 2 Supplement 1

Neural Control of Breathing

  • Poster presentation
  • Published:

Neonatal maternal separation alters development of the hypercapnic ventilatory response in awake adult rats

Mother-pup interactions during early life serve to program the circuitry orchestrating the diverse responses to stress in the offspring [1,2,3]. Long periods of daily separation from the mother (ie, 3–6 h) alter behavioural, neural, and endocrine responses to stress which persist throughout life, owing to altered development and regulation of neurones orchestrating the stress response [3,4]. These neurones include the paraventricular nucleus of the hypothalamus (PVH) and noradrenergic neurones of the locus coeruleus (LC) [3,5]. Because neurones affected by maternal separation also play an important role in ventilatory control, we tested the hypothesis that maternal separation disrupts development of the respiratory control system. This study 1)compared ventilatory responses to hypercapnia between control animals and rats subjected to maternal separation during the neonatal period, and 2)determined whether hypercapnic activation of LC and PVH neurones (as indicated by Fos mRNA expression) is affected by neonatal separation. Newborn rats were separated from their mother 3 h/day for 10 consecutive days (P3–P12). Pups were then reared in standard conditions until adulthood. Ventilatory activity was measured in awake rats using whole body plethysmography under baseline (normoxic normocapnia) and hypercapnic conditions (5% CO2 in air). At the end of the experiment, animals were sacrificed and brains were collected for subsequent quantification of Fos mRNA in the PVH and LC by in situ hybridization.

Plethysmographic measurements show that the hypercapnic venti-latory response is 30% lower in separated rats (n = 6) than in controls (n = 13). This attenuation of the response is due exclusively to a reduced increase in tidal volume, as the frequency component of the response was not affected by the neonatal treatment. In separated rats, the blunted responsiveness to hypercapnia was associated with a lack of increase in Fos mRNA levels in the PVH. However, hypercapnic exposure nearly doubled Fos mRNA expression in control rats, thereby suggesting that PVH neurons play a role in the hypercapnic ventilatory response. Conversely, hypercap-nia decreased Fos mRNA in the LC equally in both groups.

These data suggest that a neonatal stress, such as disruption of mother-infant interactions, which is not directly relevant to respiratory homeostasis may have a significant impact on development of the hypercapnic ventilatory response. These results may point to a new factor in the etiology of delays in developmental maturation in respiratory control and subsequent of respiratory disorders.


  1. Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ: Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science. 1997, 277: 1659-1662. 10.1126/science.277.5332.1659.

    Article  PubMed  CAS  Google Scholar 

  2. Caldji C, Tannenbaum B, Sharma S, Francis D, Plotsky PM, Meaney MJ: Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc Natl Acad Sci. 1998, 95: 5335-5340. 10.1073/pnas.95.9.5335.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. Francis DD, Meaney MJ: Maternal care and the development of stress responses. Curr Opin Neurobiol. 1999, 9: 128-34. 10.1016/S0959-4388(99)80016-6.

    Article  PubMed  CAS  Google Scholar 

  4. Anisman H, Zaharia MD, Meaney MJ, Merali A: Do early-life events permanently alter behavioral and hormonal responses to stressors?. Int J Dev Neurosci. 1998, 16: 149-64. 10.1016/S0736-5748(98)00025-2.

    Article  PubMed  CAS  Google Scholar 

  5. Valentino RJ, Curtis AL, Page ME, Pavcovich LA, Florin-Lechne SM: In: Catecholamines: Bridging Basic Sciences with Clinical Medicine. Edited by Goldstein D, McCarty R. AC Press;. 1998, 781-784.

    Google Scholar 

Download references


This research was approved by the Laval University Animal Care Committee and supported by the Hospital for Sick Children Foundation, Fondation de la Recherche sur les Maladies Infantiles, and Canadian Institutes for Health Research. RK. is a Parker B. Francis Fellow in Pulmonary Research.

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

About this article

Cite this article

Genest, S., Gulemetova, R., Laforest, S. et al. Neonatal maternal separation alters development of the hypercapnic ventilatory response in awake adult rats. Respir Res 2 (Suppl 1), P22 (2001).

Download citation

  • Received:

  • Published:

  • DOI: