Studies on Responses of the Upper Airway Motor Nerves to Activation of Pulmonary Vagal Afferents in the Rat

[[abstract]]The upper airway (UAW) is composed of the nasal cavity, pharynx and larynx. The patency of the UAW is primarily controlled by the respiratory-related activity of the UAW motor nerves, such as the facial, hypoglossal, superior laryngeal and recurrent laryngeal nerve. Pulmonary vagal afferents, including pulmonary vagal C-fiber (PCF) receptors, slowly adapting stretch receptors (SARs) and rapidly adapting receptors (RARs), are the main sensory afferents arising from the lungs and play an important role in regulating respiration. However, modulation of pulmonary vagal afferents on the UAW motor activity has not yet fully understood. Purpose of present dissertation was to investigate responses of the UAW motor nerves to pulmonary vagal afferent activation in the rat. At first, responses of the hypoglossal nerve to PCF receptor activation by intra-jugular capsaicin administration were examined in the anesthetized and artificially ventilated rats. The results showed that capsaicin-induced PCF receptor activation produced reflex inhibition on phasic (pre-inspiratory; Pre-I, and inspiratory; I) activity but excited tonic activity of the whole hypoglossal nerve. This raised a question whether decrease in the two branches, the medial hypoglossal branch (MHN) innervated the tongue protrudor muscles and lateral hypoglossal branch (LHN) supplied to the tongue retractor muscles was similar or dissimilar. To answer this question, the MHN and LHN were simultaneously recorded to examine their response to capsaicin treatment. The results showed that phasic activity of both hypoglossal branches was similarly reduced, while tonic activity was significantly evoked in the MHN versus LHN. To evaluate the motoneuronal activity underlying the hypoglossal discharge during PCF receptor activation, data from single fiber recording on these two hypoglossal branches revealed that decrease in phasic hypologlossal activity was mainly due to the decrease in discharge rate and a delay onset of the expiratory-inspiratory (EI) and inspiratory (I) hypoglossal motoneurons. However, tonic hypoglossal activity was resulted from the recruitment of silent hypoglossal motoneurons. Results from a further study showed that both protrusive and retractive tongue force development were reduced following intra-jugular capsaicin injection in spontaneously breathing rats. These results suggest that PCF receptor activation by capsaicin may have produced a disadvantage or even risk for the UAW patency. In contrast, activation of other pulmonary vagal afferents, such as SARs and RARs, may have produced distinct effects. Activation of SARs and RARs was achieved by changing positive end-expired pressure (PEEP). The results indicated that elevation of PEEP induced uncoupling of UAW phasic activity from the phrenic burst. This uncoupling was primarily due to a result of persistent firing of Pre-I of the UAW nerves and of the EI motoneurons during phrenic apnea caused by increasing PEEP. Data from the analysis by linear regression illustrated a differential influence of PEEP on EI motoneurons during Pre-I duration vs. I phase. Finally, blockade of glycinergic transmission by strychnine attenuated Pre-I activity of the hypoglossal nerve during control condition, and also during the advanced onset of the Pre-I activity caused by increase of PEEP and sustained lung inflation. In conclusion, the present results suggest that: (1) PCF receptor activation may produce a unfavorable modulation of the pharyngeal patency by the decrease in activity of the hypoglossal nerve and in tongue force development, (2) alteration of SARs and RARs activity by manipulating PEEP evokes an excitation on Pre-I but inhibition on I activity of the UAW motor nerves, and (3) glycinergic inhibition is probably critical for regulation of Pre-I activity of the UAW motor nerves.