Bronchopulmonary C fiber receptors in the lungs and airways transmit sensory information to the CNS to modulate respiratory pattern. The receptors are stimulated by lung autacoids such as bradykinin and prostaglandins; by exogenous chemicals such as phenyldiguanide (a serotonin structural analog) and capsaicin; by environmental toxicants such as ozone and cigarette smoke, and during severe pulmonary edema. When stimulated the bronchopulmonary C fiber receptors produce rapid shallow breathing (that may be preceded by an apnea), bradycardia, hypotension, and an increase in airway resistance. The long-term goal of this research is to characterize the central circuitry whereby activation of bronchopulmonary C fiber receptors reflexly produces a rapid shallow pattern of breathing. We have identified proximal synapse(s) in the reflex pathway in a discrete region in the nucleus tractus solitarius (NTS) (6). We have also collected preliminary data regarding distal synapses, which suggest that afferent input from the bronchopulmonary C fiber receptors ultimately modulates the activity of neurons in the ventral respiratory group (VRG). We hypothesize that to produce rapid shallow breathing, bronchopulmonary C fiber afferent input converges onto neurons in a discrete region in commissural NTS and then diverges to excite neurons in the rostral VRG that discharge in early expiration with a decrementing pattern (early E or EDEC cells). These early (EDEC) cells, in turn inhibit bulbospinal inspiratory (I) cells (to decrease the amplitude and burst duration of phrenic nerve activity), and inhibit E cells in the caudal VRG that discharge in late expiration (late E cells) and that innervate expiratory motoneurons in the spinal cord (to decrease expiratory time). Studies will be performed in urethane-anesthetized rats in which we record extracellular single unit activity in the CNS, phrenic nerve activity, tidal volume, and systematic arterial pressure. Bronchopulmonary C fiber receptors will be stimulated by injecting PDG into the right atrium.
The aims are: 1) to determine, using extracellular recording, if neurons in the NTS region (previously characterized; 6) receive excitatory input from bronchopulmonary C fiber receptors; 2) to determine the effects of bronchopulmonary C fiber receptor stimulation on the discharge patterns of early E cells (EDEC) in the rostral VRG and Botzinger complex, I cells throughout the VRG, and late E cells in the caudal VRG; and to determine, using antidromic activation, the projections of those cells, i.e. to the phrenic motor nucleus, thoracic spinal cord, vagus nerve, or the superior laryngeal nerve (SLN); 3) to determine, using cross-correlation analysis,
