The proposed experiments are designed to test the hypothesis that the lack of hypoxic respiratory depression in mice at P1-P3 results from gamma-aminobutyric acid (GABA), acting at GABAA receptors, depolarizing the resting membrane potential and thereby exciting respiratory neurons at this stage of development. Experiments are proposed in decerebrate and vagotomized mice to show that the greater respiratory drive in P1-P3 mice compared to P7-P10 pups is central in origin. Pharmacologic and genetic techniques will be used to determine the role of GABA in hypoxic hyperpnea and depression during early postnatal development in unanesthetized mice. Whole cell recordings will also be performed in brainstem slices to determine membrane potential and the reversal potential for chloride in the presence of a GABAa agonist. Changes in the chloride potential may underlie disturbances in respiratory drive and apnea in premature human newborns.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD038316-02
Application #
6351419
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Willinger, Marian
Project Start
2000-02-15
Project End
2003-01-31
Budget Start
2001-02-01
Budget End
2003-01-31
Support Year
2
Fiscal Year
2001
Total Cost
$74,256
Indirect Cost
Name
Oregon Health and Science University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239