Resiniferotoxin, a C-fiber agonist, activates a polysynaptic pathway to excite vagal cardiac neurons in the nucleus ambiguus

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Journal Article

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FASEB Journal






Previous work has shown that vagal cardiac neurons in the nucleus ambiguus (NA) do not fire spontaneously, but rather are normally silent and depend on excitatory synaptic activity to initiate and maintain their activity. One pathway may be from visceral sensory neurons. In this study we examined whether an activator of C-type sensory neurons, resiniferotoxin (RTX), can directly activate vagal cardiac neurons, and/or activate mono- or poly-synaptic pathways to vagal cardiac neurons in the NA. To test these hypotheses perforated patch clamp electrophysiological techniques were used to characterize changes in membrane current, as well as examine any alterations in synaptic activity that impinge on vagal cardiac neurons. The soma of these neurons were visualized in an in-vitro brainstem slice and identified by the presence of a fluorescent tracer that had been previously applied to their peripheral terminals surrounding the heart. DIC optics, infrared illumination and detection cameras were used to guide and position the patch pipette onto the surface of the identified neuron. RTX (10 nM) did not excite vagal cardiac neurons directly. RTX did, however, increase the frequency of miniature synaptic events (minis). When tetrodotoxin was applied to block polysynaptic pathways the increase in minis was inhibited. These results demonstrate that RTX does not influence vagal cardiac neurons directly, but RTX does activate a polysynaptic pathway to excite these neurons, and this pathway is contained within this brainstem slice.

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