Respiration is controlled by a complex neural system in which the activities of respiratory pattern generators within the central nervous system are modified by a variety of peripheral sensory mechanisms (chemoreceptors and mechanoreceptors) and central feedback loops. Progress in understanding the operation of this neuronal network in both health and disease requires greater insight into the cellular components and details of how they are connected. The proposed research focuses on the central pathways of the different pulmonary receptors (slowly adapting stretch receptors, pulmonary rapidly adapting receptors, and pulmonary and bronchial C-fibers) and the way that information arising from these receptors affects the activity of neurons in the brainstem and thus the magnitude and timing of ventilation, as well as airway diameter. The central pathways will be studied using both microstimulation and electrophysiological recording techniques. The axonal projections of the second order relay cells for pulmonary stretch receptors will be traced to other areas of the brainstem known to contain cells affected by lung inflation, including the important expiratory areas of the medulla and a region of the pons that may play an important role in the neurogenesis of eupnea. Although rapidly adapting receptors have been implicated in many reflexes associated with pathological states, nothing is known about the characteristics of their relay neurons. Areas identified as containing fine terminals of rapidly adapting receptors will be explored to find neurons whose firing is related to the activation of rapidly adapting receptors. The slowly adapting stretch receptors of the trachea have been implicated as being important in the generation of coughing. Nothing is known about their central projections or relay neurons. The projections will be determined by the technique of antidromic mapping and the relay cells identified by microelectrode recordings. Strong evidence that information from pulmonary and bronchial C-fibers is important in the control of respiration in both normal and pathological conditions has recently been advanced. The projections and relay neurons of these receptors have not been identified. This will be determined by antidromic mapping and microelectrode recordings. Knowledge of the connections and behaviors of the neural elements subserving reflexes from pulmonary and airway receptors should contribute to understanding their roles in the control of respiratory function in normal and disordered states.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL036621-01
Application #
3351723
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1986-07-01
Project End
1990-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Kubin, Leszek; Alheid, George F; Zuperku, Edward J et al. (2006) Central pathways of pulmonary and lower airway vagal afferents. J Appl Physiol 101:618-27
Kubin, L; Kimura, H; Davies, R O (1991) The medullary projections of afferent bronchopulmonary C fibres in the cat as shown by antidromic mapping. J Physiol 435:207-28
Kubin, L; Davies, R O (1988) Sites of termination and relay of pulmonary rapidly adapting receptors as studied by spike-triggered averaging. Brain Res 443:215-21
Altschuler, S M; Davies, R O; Pack, A I (1987) Role of medullary inspiratory neurones in the control of the diaphragm during oesophageal stimulation in cats. J Physiol 391:289-98