The objectives of this research are to locate the site of brainstem neurons and to identify the interconnections and interactions which are responsible for generating the patterns of respiratory motor output. A feature of the respiratory motor output in the decerebrate cat is the high degree of synchronization of inspiratory activity on the very short time scale of 0.01 seconds (100 Hz). Phrenic and intercostal motoneurons in the spinal cord and hypoglossal and recurrent laryngeal motoneurons in the brainstem fire in an inspiratory unison every 10 milliseconds. Membrane potentials of inspiratory neurons of the dorsal respiratory group oscillate at 100 Hz due to excitatory synaptic input while, simultaneously, membrane potentials of the expiratory neurons of the ventral respiratory group oscillate at 100 Hz but 180 degrees out of phase due to inhibitory input. Having confirmed the early work of Dittler and Garten in the dog and rabbit that the frequency of synchronization is proportional to body temperature, the investigator intends to demonstrate with this proposed research in the decerebrate cat and rabbit: that the temperature sensitivity of the 100 Hz synchronization can be exploited to locate the sites of respiratory neurons and to identify their role in the generation of the respiratory pattern; that the 100 Hz synchrony provides a unique internal time marker allowing one to refine the classification of inspiratory neurons based on the phase of their activity relative to the 100 msec clock and allowing one to give electrical stimuli precisely timed relative to the 10 millisecond clock; that factors which affect synchrony affect other commonly observed features of the respiratory pattern. The protocols described are designed to exploit the temperatures sensitivity of high-frequency synchrony in the exploration of the network of neurons and connections involved in respiratory pattern generation by cooling decerebrate animals to 30 degrees C and heating focal brainstem sites with radio frequency current. They are designed to relate this work on inspiratory synchronization to that of others in which a variety of anesthetics and recording signal analysis techniques have been used. And finally, these experiments are designed to demonstrate the significance or insignificance of high-frequency synchrony in the generation of the respiratory pattern.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL026176-08
Application #
3338496
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1980-07-01
Project End
1994-09-29
Budget Start
1991-09-30
Budget End
1992-09-29
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143