Our ultimate goal is to determine the roles of the different types of medullary respiratory neurons in initiating, sustaining and terminating apneas. By extracellular recording of their activity in intact unanesthetized cats we will identify the influence of changes in state of arousal, carbon dioxide, oxygenation and blood pressure on the activity of these neurons. We will focus on three different areas.
AIM 1 entails the study of the responses of medullary respiratory neurons to carbon dioxide in wakefulness and in NREM and REM sleep employing a preparation we've developed utilizing ventilator-induced apnea. We will describe the activation thresholds of the various neurons to carbon dioxide as well as the pattern of discharge near the thresholds.
AIM 2 focuses on hypoxia-induced periodic breathing. This is a pattern of waxing and waning (hypopneas) ventilatory periods induced in cats by mild hypoxia. It is a destabilized breathing rhythm which is often a precursor to apnea. We will record medullary respiratory neurons to determine their roles in producing this pattern. These studies also will be done in wakefulness, NREM and REM sleep.
AIM 3 centers on interactions between blood pressure and breathing. Changes in blood pressure could be a significant factor in causing destabilized breathing since they often accompany hypopneas and apnea. We will determine whether increases and decreases in blood pressure, some produced pharmacologically and some occurring spontaneously, alter the activity of medullary respiratory neurons. In so doing we will identify neurons which could mediate the ventilatory effects of blood pressure changes. These studies will be done in wakefulness and NREM and REM sleep to detect stat effects. Overall, our studies will produce new information about the basic properties of medullary respiratory neurons and their potential roles in initiating, sustaining and terminating hypopneas and apneas in wakefulness and sleep.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL062589-02
Application #
6184758
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Program Officer
Kitt, Cheryl A
Project Start
1999-05-01
Project End
2003-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
2
Fiscal Year
2000
Total Cost
$268,803
Indirect Cost
Name
University of Wisconsin Madison
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Lovering, Andrew T; Fraigne, Jimmy J; Dunin-Barkowski, Witali L et al. (2006) Medullary respiratory neural activity during hypoxia in NREM and REM sleep in the cat. J Neurophysiol 95:803-10
Dunin-Barkowski, Witali L; Sirota, Mikhail G; Lovering, Andrew T et al. (2006) Precise rhythmicity in activity of neocortical, thalamic and brain stem neurons in behaving cats and rabbits. Behav Brain Res 175:27-42
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Orem, John; Lovering, Andrew T; Dunin-Barkowski, Witali et al. (2002) Tonic activity in the respiratory system in wakefulness, NREM and REM sleep. Sleep 25:488-96
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