Orexinergic actions modify occurrence of slow inward currents on neurons in the pedunculopontine nucleus

Orexins are neuromodulatory peptides of the lateral hypothalamus which regulate homeostatic mechanisms including sleep-wakefulness cycles. Orexinergic actions stabilize wakefulness by acting on the nuclei of the reticular activating system, including the pedunculopontine nucleus. Orexin application to pedunculopontine neurons produces a noisy tonic inward current and an increase in the frequency and amplitudes of excitatory postsynaptic currents. In the present project, we investigated orexinergic neuromodulatory actions on astrocyte-mediated neuronal slow inward currents of pedunculopontine neurons and their relationships with tonic currents by using slice electrophysiology on preparations from mice. We demonstrated that, in contrast to several other neuromodulatory actions and in line with literature data, orexin predominantly elicited a tonic inward current. A subpopulation of the pedunculopontine neurons possessed slow inward currents. Independently from the tonic currents, actions on slow inward currents were also detected, which resembled other neuromodulatory actions: if slow inward currents were almost absent on the neuron, orexin induced an increase of the charge movements by slow inward currents, whereas if slow inward current activity was abundant on the neurons, orexin exerted inhibitory action on it. Our data support the previous findings that orexin elicits only inward currents in contrast with cannabinoid, cholinergic or serotonergic actions. Similar to the aforementioned neuromodulatory actions, orexin influences slow inward currents in a way depending on control slow inward current activity. Furthermore, we found that orexinergic actions on slow inward currents are similarly independent from its actions on tonic currents, as it was previously found with other neuromodulatory agonists.