Little is currently known about the neural development of the respiratory pattern generator. Development can be viewed in two ways; first, with evolution across species and second with maturation with a single species. Early air-breathing species represent an attractive model in both regards. Although these species use a completely different method to ventilate their lungs (the buccal force pump) the mechanisms controlling respiratory timing intervals are remarkably similar to that in mammals. Thus, the timing module for respiration is likely to already have been developed in these primitive air-breathers. With evolution it is the circuits that shape the final respiratory burst that must have changed, as the mechanical act of breathing moved from the buccal force pump to suctional breathing produced by the diaphragm in mammals. One current view as to the mechanism for respiratory timing in mammals is that it is produced by a neural network, in which post-inspiratory cells plays a critical role. It will be interesting to determine whether a post-inspiratory phase is present also in early breathing species. That this is present is supported by our preliminary studies in the larval form of Rana catesbeiana (tadpole). Studies in these species provide, moreover, a model system in which to study development of the underlying neural mechanisms. Their maturational development is well characterized and there are 25 distinct stages recognized. During development there are distinct alterations in the neural output related to ventilation with increasing complexity in the characteristics of the neural burst for lung ventilation. The post-inspiratory phase seems to arise relatively late in development. Certain of the maturational changes in tadpole in the neural activity related to ventilation parallel the changes described in, the albeit limited, developmental studies in mammals. It is our goal to utilize this development model (tadpole) to study how the pattern generator for respiration arises during maturation. Our focus is initially on studying the characteristics of the changes in neural output with maturation, an essential descriptive step. Thereafter we will study the changes in the role of fast synaptic inhibition, the alterations in the patterns of synaptic input into the relevant motoneurons and changes in the types of promotor cells present. The results we obtain will be interpreted within the framework of the increasing body of knowledge as to neural development in this much studied model. These studies at the level of the development of the neural circuitry are an essential prerequisite to future studies of the changes in intrinsic properties of the relevant neurons and how such changes are programmed at the level of the genome.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL049486-01A2
Application #
2225559
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1994-04-01
Project End
1997-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Liao G-S; Kubin, L; Galante, R J et al. (1996) Respiratory activity in the facial nucleus in an in vitro brainstem of tadpole, Rana catesbeiana. J Physiol 492 ( Pt 2):529-44
Galante, R J; Kubin, L; Fishman, A P et al. (1996) Role of chloride-mediated inhibition in respiratory rhythmogenesis in an in vitro brainstem of tadpole, Rana catesbeiana. J Physiol 492 ( Pt 2):545-58