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Volume 2 Supplement 1

Neural Control of Breathing

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Serotonergic modulation of respiratory neural activity during tadpole development

The respiratory physiology of bullfrogs undergoes important modifications during development [1,2,3]. The dramatic changes in the partitioning of gas exchange function between lungs and gills during development require important alterations in the neural mechanisms controlling ventilation [4,5]. Yet, the mechanisms at the basis of these changes in respiratory motor behaviour remain poorly understood.

Hilaire and Duron proposed that maturation of the mammalian respiratory network may be defined, at least partly, by serotonergic modulatory processes [6]. To test the hypothesis that serotonergic modulation of respiratory neural activity changes during tadpole development, the effects of serotonin (5-HT) on neural correlates of respiratory activity were assessed using an in vitro brainstemspinal cord preparation.

Preparations from tadpoles of developmental stages varying between TK stagesVI and XXV were superfused with mock CSF containing 5-HT concentrations ranging from 0–25 μM. Neural correlates of gill and lung ventilation were recorded extracellularly from cranial nerve rootletsV andX.

In younger tadpoles (facultative air breathers; TK stages VI-XV) 5-HT bath application attenuated the frequency and amplitude of respiratory-related motor output (both fictive gill and lung ventilation), an effect most notable at high concentrations. In more mature animals (obligate air breathers; TK stages XVI-XXV), the effects of 5-HT bath application on fictive lung ventilation was bi-phasic. Fictive lung ventilation frequency was enhanced at low 5-HT concentrations (0.5 μ) and was depressed by higher 5-HT concentration. Moreover, 5-HT-induced attenuation of fictive gill ventilation was stronger in obligate air breathers than in preparations from younger tadpoles.

These results indicate that serotonergic modulation of respiratory activity changes substantially during tadpole development. Such changes in modulatory influences may contribute to the maturation of the respiratory control system in this species.


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R. Kinkead is a Parker B. Francis Fellow in Pulmonary Research. This research was supported by the National Science and Engineering Research Council of Canada.

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Gulemetova, R., Kinkead, R. Serotonergic modulation of respiratory neural activity during tadpole development. Respir Res 2 (Suppl 1), P23 (2001).

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