GABA-ergic neurotransmission in the nucleus of the solitary tract modulates cough in the cat

Abstract

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.

Keywords: Airway defense; Baclofen; Cough control; Microinjection; Muscimol.

Fig. 1.

Reconstruction of microinjection sites. Stars represent highlighted positions of the micropipette tip during microinjections of GABA, muscimol and baclofen in the rostral (rNTS; +1.2 mm to the obex) and caudal nucleus of the solitary tract (cNTS; −1.1 mm to the obex) as determined by fluorescent marker. Reference points: comNTS, 12, central canal, medullary surface for the cNTS; TS, NTS, 12, Int, the bottom of the 4th ventricle, medullary surface for the rNTS. Microinjections of GABA. All 14 microinjection locations were found within or near the commissural subnucleus of the NTS in the cNTS. All 12 microinjections were positioned in or near ventrolateral subnucleus of the NTS in the rNTS.Microinjections of muscimol. All 6 locations where muscimol was delivered in or near comNTS were identified. In the rNTS 5 out of 6 microinjection locations were positively identified in the ventrolateral region of the NTS. Microinjections of baclofen. All 10 Baclofen microinjections were positioned in or near comNTS in the cNTS. All 12 rNTS microinjection were identified in the area of TS and ventrolateral region of the NTS. 12: hypoglossal ncl., comNTS: commissural subnucleus of the NTS, GR: gracile ncl., Int: ncl. intercalatus, NTS: ncl. tractus solitarius, TS: tractus solitaries Inset photographs demonstrate the process. The arrows ‘injection’ point out light spots of a spread of fluorescent marker.

Fig. 2.

Changes in tracheobronchial cough induced by microinjections of GABA, muscimol and baclofen into the rostral NTS Open bars represent percentages of control (100%) within 7 min post-microinjections, gray bars recovery data (20–200 min following microinjections depending on the time when the cough recovery occurred). GABA and baclofen microinjections were bilateral, muscimol was delivered unilaterally. CN: number of coughs; DIA: amplitudes of the diaphragm EMG; C: contralateral to the microinjection; I: ipsilateral to the microinjection; ABD: amplitudes of the abdominal EMG; EP I: inspiratory amplitudes of esophageal pressure; EP E: expiratory amplitudes of esophageal pressure during cough. *, **, ***: p < 0.05, 0.01, 0.001 compared to the control data; ⁺, ⁺⁺: p < 0.05, 0.01 compared to the recovery data, respectively.

Fig. 3.

Representative examples of coughing changes induced by microinjections of GABA-ergic agents into the caudal (cNTS) and rostral NTS (rNTS). GABA in cNTS only reduced cough number. In the rNTS cough number, expiratory cough efforts and for GABA and muscimol also inspiratory cough efforts were decreased. Muscimol microinjections were unilateral and the effects on ABD were equal, while suppression of DIA was more pronounced at the contralateral side. Post-microinjection cough trials were executed within 2–5 min for GABA and 2–7min post-injection time window for muscimol and baclofen. ∫ : moving average; DIA: the diaphragm EMG; ABD: the abdominal muscles EMG; EP: esophageal pressure; BP: arterial blood pressure; i: ipsilateral; c: contralateral.