Hcrtr2, also known as Orexin receptor 2 (OX2R), is a G-protein-coupled receptor. The endogenous ligands for Hcrtr2 are hypocretin/orexin neuropeptides. Hcrtr2 is strongly linked to sleep-wake control and is involved in the endogenous sleep-wake regulatory circuitry. The broad projections of hypocretin/orexin-producing neurons and the differential expression of Hcrtr2 in their projection fields suggest its distinct role in physiological processes. Genetic models, such as gene knockout mouse models, can be valuable for studying Hcrtr2's function [1].

In a study on mice, inactivation of Hcrtr2 in dopaminergic neurons led to hyperarousal, enhanced cognition, but impaired inhibitory control. DAHcrtr2-deficient mice showed increased theta electroencephalographic (EEG) activity in wakefulness and rapid-eye-movement sleep, more time in an active substate of wakefulness, and prolonged rapid-eye-movement sleep. They also had enhanced theta-gamma phase-amplitude coupling and more pronounced EEG activity surges in novel environments, indicating increased alertness. These findings establish a link between Hcrtr2-mediated neurotransmission and theta oscillations, as well as its role in attentional and executive functions relevant to disorders like narcolepsy, attention-deficit/hyperactivity disorder, and Parkinson's disease [2].

In conclusion, Hcrtr2 is a key player in sleep-wake regulation. The study of Hcrtr2 knockout mouse models has revealed its role in physiological processes related to arousal, cognition, and inhibitory control, providing insights into the pathophysiology of certain neurological and psychiatric disorders.