Central GABAergic Modulation of Physostigmine-Induced Airway Constriction in Male Ferrets: A Bilateral Dorsal Motor Nucleus Microinjection Study

The dorsal motor nucleus of the vagus (DMV) is a key brainstem structure involved in autonomic integration and vagal regulation of thoracic organs. This study examined whether localized GABA microinjection into the DMV modulates cholinergically induced airway mechanical responses in anesthetized male ferrets. Bilateral stereotaxic microinjections of GABA (10 µmol; 25–50 nL) were performed in the DMV (AP −12.6 mm, ML 0 mm, DV −7.6 mm). Airway mechanics were evaluated by measuring tracheal segment pressure (Ptseg), lung resistance (RL), and dynamic compliance (Cdyn) at baseline, following intravenous physostigmine (100 µg/kg), and after GABA administration. Physostigmine significantly increased Ptseg and RL (p < 0.01), indicating cholinergically mediated airway constriction. GABA microinjection attenuated these effects and significantly reduced Cdyn (p < 0.05). Under controlled mechanical ventilation, these findings support a central inhibitory influence of DMV GABAergic signaling on vagally mediated airway responses during cholinergic activation. This study provides mechanistic proof-of-concept evidence for central modulation of airway mechanics and highlights the role of brainstem inhibitory circuits in autonomic respiratory regulation.