Synaptic activation of cardiac vagal neurons by capsaicin sensitive and insensitive sensory neurons

Abstract

Little is known about the central circuitry involved in the sensory activation of cardioinhibitory vagal neurons (CVNs). To study the polysynaptic activation of CVNs from sensory neurons the postsynaptic currents in CVNs in the dorsal motor nucleus of the vagus (DMNX) were evoked by stimulation of the vagus nerve. In addition, the role of afferent A-fiber and C-fiber activation of CVNs was examined. CVNs were identified by a retrograde fluorescent tracer and were studied in an in vitro slice preparation using patch-clamp electrophysiology. Stimulation of the vagus nerve evoked excitatory postsynaptic currents in CVNs that were reversibly blocked by the NMDA antagonist d-2-amino-5-phosphonovalerate (AP5) and the non-NMDA antagonist 6-cyano-7-nitroquionoxaline-2,3-dione (CNQX). Vagal stimulation also evoked inhibitory postsynaptic currents (IPSCs) that were reversibly blocked by the GABA A antagonist gabazine. Capsaicin, which inactivates C-fibers, was used to examine the role of afferent A-fibers and C-fibers in the synaptic activation of CVNs. Capsaicin significantly ( P<0.05) reduced the amplitude of evoked glutamatergic and GABAergic postsynaptic currents by 59% and 76%, respectively. The latency of the GABAergic response increased significantly ( P<0.05) in the presence of capsaicin from 36±1 to 41±1 ms while the latency of the glutamatergic response (44±3 ms) was unaffected. There are three conclusions from this study. Stimulation of vagal afferents evokes both GABAergic and glutamatergic responses in CVNs, C-type afferent fibers are critical to the afferent stimulation of CVNs, and the A-fiber GABAergic pathway to CVNs may be more complex than the C-fiber GABAergic pathway.