Orexin A activates locus coeruleus cell firing and increases arousal in the rat

TLDR

Orexin neuropeptides are localized in the lateral hypothalamus, where they influence feeding yet project widely, indicating a complex physiological role. The study investigates how orexin A modulates rat arousal using anatomical mapping, electrophysiology, and behavioral assays. The authors combined tissue localization, electrophysiological recordings, and behavioral tests to assess orexin A effects. Orexin A densely innervates the locus coeruleus, elevating noradrenergic neuron firing, increasing arousal and locomotor activity, modulating neuroendocrine function, and appearing to orchestrate the sleep‑wake cycle.

Abstract

The localization of orexin neuropeptides in the lateral hypothalamus has focused interest on their role in ingestion. The orexigenic neurones in the lateral hypothalamus, however, project widely in the brain, and thus the physiological role of orexins is likely to be complex. Here we describe an investigation of the action of orexin A in modulating the arousal state of rats by using a combination of tissue localization and electrophysiological and behavioral techniques. We show that the brain region receiving the densest innervation from orexinergic nerves is the locus coeruleus, a key modulator of attentional state, where application of orexin A increases cell firing of intrinsic noradrenergic neurones. Orexin A increases arousal and locomotor activity and modulates neuroendocrine function. The data suggest that orexin A plays an important role in orchestrating the sleep-wake cycle.