Synaptic and intrinsic activation of respiratory GABAergic neurons in the brainstem

Abstract

Respiratory sinus arrhythmia is mediated by inspiratory-evoked increases in GABAergic neurotransmission to cardiac vagal neurons (CVNs) that control heart rate. However, the mechanisms responsible for the sources and activation of the inspiratory-related GABAergic neurotransmission to CVNs are unknown. We identified a population of GABAergic neurons in the ventrolateral medulla that are activated during inspiration in a slice preparation that retains rhythmic respiratory activity. This population of inspiratory-activated GABAergic neurons receives inspiratory-related excitatory events that were blocked by the glutamatergic antagonists, NMDA and AMPA/kainate receptor antagonists AP-5 and CNQX, respectively. The nicotinic acetylcholine receptor antagonists, DHbE, 100microM and a-BTX, 100nM had no significant effect. A subset of inspiratory GABAergic neurons continue to fire in the presence of CNQX/AP-5, suggesting they may have the characteristics of a respiratory pacemaker neuron. The pacemaker cells not inhibited by CNQX were insensitive to cadmium. The results from this study demonstrate the existence of a population of GABAergic inspiratory neurons in the ventrolateral medulla that likely project to CVNs, receive increased glutamatergic neurotransmission during inspiration, and a subset of these GABAergic neurons have respiratory pacemaker properties.