Hypocretin‐1 (orexin A) enhances the GABAergic pathway from the lateral paragigantocellular nucleus to cardiac vagal neurons in the nucleus ambiguus

Hypocretins (orexins) are hypothalamic neuropeptides that play a crucial role in regulating sleep/wake states and autonomic functions including parasympathetic cardiac activity. We have recently demonstrated stimulation of the lateral paragigantocellular nucleus (LPGi), the nucleus which is thought to play a role in rapid eye movement sleep control, evokes inhibitory current in preganglionic cardiac vagal neurons (CVNs) in the nucleus ambiguus. In this study we test the hypothesis that hypocretin‐1 modulates inhibitory neurotransmission to CVNs evoked by stimulation of the LPGi. GABAergic activity to CVNs was examined using whole‐cell patch‐clamp recordings in an in‐vitro brain slice preparation in rats. Activation of hypocretin‐1 receptors produced a dose‐dependent and long‐term facilitation of GABAergic postsynaptic current evoked by electrical stimulation of the LPGi. The action of hypocretin‐1 was blocked by the hypocretin‐1 receptor antagonist SB 334867. Facilitation of LPGi‐evoked GABAergic current in CVNs could be the mechanism by which hypocretin‐1 affects parasympathetic cardiac function and heart rate particularly during rapid eye movement sleep.