Extracellular Calcium Contributes to Orexin-Induced Postsynaptic Excitation of the Rat Locus Coeruleus Neurons

Noradrenergic neurons of the locus coeruleus (LC) receive projection from hypothalamus orexinergic neurons and express orexin receptor type 1 (OXR1). Orexin-A has a regulatory effect on feeding, sleep, arousal, reward processing, and drug addiction. Orexinergic neurons make excitatory afferent to the LC neurons. However, the underlying mechanism of the orexin effect on LC neurons is not completely discerned. In the current study, the contribution of calcium to orexin-induced excitation of the rat LC neurons was studied in brainstem slice preparations by the whole-cell patch-clamp method. The application of orexin increased the firing rates of action potentials (APs) in normal artificial cerebrospinal fluid (aCSF). In low Ca 2+ aCSF orexin enhanced the firing rate higher than in normal aCSF. Orexin increased the mean amplitude of the depolarization and reduced the afterhyperpolarization (AHP) following each action potential in low Ca 2+ aCSF compared to normal aCSF. Furthermore, the frequency of spontaneous excitatory postsynaptic currents (sEPSC) is enhanced by orexin in low external Ca 2+ compared to normal aCSF but the amplitude of sEPSCs did not change. Current results have unraveled that orexin-A has an excitatory effect on the rat LC neurons.