The importance of neurons in the nucleus of the solitary tract (NTS) in the production of coughing was tested by microinjections of the nonspecific glutamate receptor antagonist kynurenic acid (kyn; 100 mM in artificial cerebrospinal fluid) in 15 adult spontaneously breathing anesthetized cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airway. Electromyograms (EMG) were recorded from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles. Bilateral microinjections of kyn into the NTS rostral to obex [55 ± 4 nl total in 2 locations ( = 6) or 110 ± 4 nl total in 4 locations ( = 5)], primarily the ventrolateral subnucleus, reduced cough number and expiratory cough efforts (amplitudes of ABD EMG and maxima of esophageal pressure) compared with control. These microinjections also markedly prolonged the inspiratory phase, all cough-related EMG activation, and the total cough cycle duration as well as some other cough-related time intervals. In response to microinjections of kyn into the NTS rostral to the obex respiratory rate decreased, and there were increases in the durations of the inspiratory and postinspiratory phases and mean blood pressure. However, bilateral microinjections of kyn into the NTS caudal to obex as well as control vehicle microinjections in the NTS location rostral to obex had no effect on coughing or cardiorespiratory variables. These results are consistent with the existence of a critical component of the cough rhythmogenic circuit located in the rostral ventral and lateral NTS. Neuronal structures of the rostral NTS are significantly involved specifically in the regulation of cough magnitude and phase timing. The nucleus of the solitary tract contains significant neuronal structures responsible for control of ) cough excitability,) motor drive during cough, ) cough phase timing, and) cough rhythmicity. Significant elimination of neurons in the solitary tract nucleus results in cough apraxia (incomplete and/or disordered cough pattern). The mechanism of the cough impairment is different from that for the concomitant changes in breathing.

The modulation of cough by microinjections of codeine in 3 medullary regions, the solitary tract nucleus rostral to the obex (rNTS), caudal to the obex (cNTS) and the lateral tegmental field (FTL) was studied. Experiments were performed on 27 anesthetized spontaneously breathing cats. Electromyograms (EMG) were recorded from the sternal diaphragm and expiratory muscles (transversus abdominis and/or obliquus externus; ABD). Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. Bilateral microinjections of codeine (3.3 or 33 mM, 54 ± 16 nl per injection) in the cNTS had no effect on cough, while those in the rNTS and in the FTL reduced coughing. Bilateral microinjections into the rNTS (3.3 mM codeine, 34 ± 1 nl per injection) reduced the number of cough responses by 24% (P < 0.05), amplitudes of diaphragm EMG by 19% (P < 0.01), of ABD EMG by 49% (P < 0.001) and of expiratory esophageal pressure by 56% (P < 0.001). Bilateral microinjections into the FTL (33 mM codeine, 33 ± 3 nl per injection) induced reductions in cough expiratory as well as inspiratory EMG amplitudes (ABD by 60% and diaphragm by 34%; P < 0.01) and esophageal pressure amplitudes (expiratory by 55% and inspiratory by 26%; P < 0.001 and 0.01, respectively). Microinjections of vehicle did not significantly alter coughing. Breathing was not affected by microinjections of codeine. These results suggest that: 1) codeine acts within the rNTS and the FTL to reduce cough in the cat, 2) the neuronal circuits in these target areas have unequal sensitivity to codeine and/or they have differential effects on spatiotemporal control of cough, 3) the cNTS has a limited role in the cough suppression induced by codeine in cats.

The effect of volume-related feedback and output airflow resistance on the cough motor pattern was studied in 17 pentobarbital anesthetized spontaneously-breathing cats. Lung inflation during tracheobronchial cough was ventilator controlled and triggered by the diaphragm electromyographic (EMG) signal. Altered lung inflations during cough resulted in modified cough motor drive and temporal features of coughing. When tidal volume was delivered (via the ventilator) there was a significant increase in the inspiratory and expiratory cough drive (esophageal pressures and EMG amplitudes), inspiratory phase duration (CTI), total cough cycle duration, and the duration of all cough related EMGs (Tactive). When the cough volume was delivered (via the ventilator) during the first half of inspiratory period (at CTI/2 - early over inflation), there was a significant reduction in the inspiratory and expiratory EMG amplitude, peak inspiratory esophageal pressure, CTI, and the overlap between inspiratory and expiratory EMG activity. Additionally, there was significant increase in the interval between the maximum inspiratory and expiratory EMG activity and the active portion of the expiratory phase (CTE1). Control inflations coughs and control coughs with additional expiratory resistance had increased maximum expiratory esophageal pressure and prolonged CTE1, the duration of cough abdominal activity, and Tactive. There was no significant difference in control coughing and/or control coughing when sham ventilation was employed. In conclusion, modified lung inflations during coughing and/or additional expiratory airflow resistance altered the spatio-temporal features of cough motor pattern via the volume related feedback mechanism similar to that in breathing.

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GABA, muscimol, and baclofen were microinjected into the rostral (rNTS) and caudal solitary tract nucleus (cNTS) in 24 anesthetized cats. Electromyograms (EMGs) of diaphragm (DIA) and abdominal muscles (ABD), blood pressure and esophageal pressure (EP) were recorded and analysed. Bilateral microinjections of 1 mM GABA (total 66 ± 4 nl), 1 mM baclofen (64 ± 4 nl) and unilateral microinjections of 0.5 mM muscimol (33 ± 1 nl) in the rNTS significantly reduced cough number (CN), amplitudes of ABD EMGs, expiratory EP, and prolonged the duration of the cough inspiratory phase. GABA microinjections decreased the amplitudes of cough-related DIA EMGs and inspiratory EP; muscimol microinjections decreased the cough DIA EMG on the contralateral side. Only microinjections of GABA into the cNTS suppressed CN. In some cases, microinjections prolonged the inspiratory phase, lowered respiratory rate, changed the depth of breathing, and increased blood pressure and heart rate. Our results confirm that GABA-ergic inhibitory mechanisms in the rNTS can regulate coughing in the anesthetized cat.