MECHANISMS OF RESPIRATORY MUSCLE COORDINATION

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The recruitment of more and more inspiratory muscles to activity as respiratory stress increases seems to be a fundamental strategy in mammalian respiratory behavior. Coordinated activation of the various respiratory muscles in order to achieve particular patterns of breathing is a likely means of minimizing the energetic or other costs of breathing, especially in stress or disease situations. The objective of this proposal is to identify and characterize central neural and peripheral reflex mechanisms which underly the simultaneous excitation of inspiratory muscles. High frequency oscillations (HFO's) in the frequency range 4-120 Hz in respiratory motor nerve mass discharge activities will be identified using power spectral and coherence spectral analysis techniques. HFO's will be considered as "markers" of common drive inputs to two or more motoneuron pools when they are correlated in the corresponding nerve activities. Phrenic, various external intercostal, hypoglossal, and recurrent laryngeal nerve activities will be analyzed. The effects of various stimuli on the presence of HFO's in individual nerve activity and, particularly, on the distribution of correlated HFO's among the inspiratory nerves will be assessed. Stimuli will include: hypercapnia, hypoxia, neural inputs from the ventral medullary surface (altered by local cooling or drug applications), and drives from subthalamic motor areas. The effects of lesioning of ascending spinal afferent tracts on HFO's will be determined, and the relationship between HFO's in phrenic nerve activity and the firing patterns of single phrenic fibers will be studied. In addition, all the above studies except the last will be done in kittens at ages ranging from 5-60 days in order to determine the postnatal development of respiratory motor nerve HFO's. From these data we will determine the functional characteristics of mechanisms which are likely to be important in the coordination of respiratory muscle activities and determine their relative importance in responding to chemical and other stresses. We would draw inferences regarding the neuroanatomical loci responsible for the generation and propogation of the HFO's. Finally, we would assess the maturation of central neural structures that are involved in the production HFO's and may be components of central respiratory rhythm generator(s).