Previous studies have revealed that orexin may actively participate in central motor control. The gigantocellular reticular nucleus (Gi) is a key element of the brainstem motor inhibitory system. The descending orexinergic projections also reach Gi region, and microinjection of orexin into Gi causes robust muscle tone inhibition. However, the modulation effects of orexin on Gi neurons remain unclear. In the present study, using whole-cell patch-clamp recordings, we initially observed that orexin elicited an inward current in Gi neurons at a holding potential of -70mV in a concentration-dependent manner. By combining electrophysiology with neuropharmacological methods, we further determined that the orexin-induced inward current was directly mediated by the activation of postsynaptic orexin-1 and orexin-2 receptors. Moreover, orexin did not affect the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents in Gi neurons, which suggests that orexin had no effects on neurotransmission to these neurons. Therefore, the direct excitatory effect of orexin on an inhibitory motor structure, the Gi, was reported in the present study. This modulation may be integrated into the role of orexin in central motor control.

The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.

The relationship between orexin/hypocretin and rapid eye movement (REM) sleep remains elusive. Here, we find that a proportion of orexin neurons project to the sublaterodorsal tegmental nucleus (SLD) and exhibit REM sleep-related activation. In SLD, orexin directly excites orexin receptor-positive neurons (occupying ~3/4 of total-population) and increases gap junction conductance among neurons. Their interaction spreads the orexin-elicited partial-excitation to activate SLD network globally. Besides, the activated SLD network exhibits increased probability of synchronized firings. This synchronized excitation promotes the correspondence between SLD and its downstream target to enhance SLD output. Using optogenetics and fiber-photometry, we consequently find that orexin-enhanced SLD output prolongs REM sleep episodes through consolidating brain state activation/muscle tone inhibition. After chemogenetic silencing of SLD orexin signaling, a ~17% reduction of REM sleep amounts and disruptions of REM sleep muscle atonia are observed. These findings reveal a stabilization role of orexin in REM sleep.