Orexin

Nature staff discuss how a newly approved orexin-targeting narcolepsy drug could enable therapies for other neurological conditions, and examine human brain organoids that have remained viable for more than five years. The episode connects sleep medicine, therapeutic neuroscience, and long-term models of human brain development.

…to the wake-promoting neuropeptide orexin, suggesting that L6-Drd1a neurons play an important role in sensory processing, brain state modulation, attention, and cognition (Hoerder-Suabedissen et al., 2018; Zolnik et al., 2023). In the medial prefrontal cortex (mPFC), whether these neurons play an analogous role in gating cortical arousal remains poorly understood. Thus, we investigated the effects of ‘silencing’ L6-Drd1a neurons in a

Hypocretin(orexin)-producing neurons in the lateral hypothalamic area are important for sleep regulation and their damage manifests clinically as narcolepsy in humans. In animal experiments, extensive lesions of these neurons confirmed and clarified their physiological importance. Smaller, partial lesions of hypocretinergic neurons may uncover more subtle mechanisms of function of hypocretin system and may help understand more delicate processes in early stages of pathogenesis of narcolepsy. In a lesioned group of rats (N=9) bilateral injections of hypocretin-2-saporin (Hcrt2-SAP) conjugate in

…specific compounds (e.g., Carbachol, orexin), network activity can be manipulated to switch to a wake state. To reduce the costs and ethical issues related to in vitro studies and to be more sustainable in research, i

Orexin binds G-protein-coupled receptors, orexin receptor 1 (Ox1R) and 2 (Ox2R). These receptors modulate diverse brain functions, such as sleep and metabolism, with their wide expression throughout the brain. Previous in vitro studies have found that Ox2R works in both Gq and Gi-coupled signaling pathways, indicating excitatory and inhibitory functions respectively. In vivo studies, however, the inhibitory role has yet to be discerned, whereas the excitatory function has been elucidated in numerous reports. Consequently, Ox2R is predominantly recognized for eliciting only excitatory signals i

Complex interactions between serotonin (5-hydroxytriptamine) and orexin (hypocretin) systems in the CNS modulate diverse physiological processes, including mood regulation, energy homeostasis, and spontaneous physical activity. A portion of this interaction may be explained by G protein-coupled receptor oligomerization, which might influence agonist affinity, efficacy, trafficking, and signal transduction. Orexin receptor 1 (OX1) and 5-hydroxytriptamine 2C receptor (5-HT2C) co-express in diverse neuronal populations and are involved in pathological conditions such as anxiety and eating disorde

Subplate neurons are among the earliest generated neurons in the cerebral cortex that orchestrate the development of the intra and extracortical connections. A large proportion of these neurons undergoes cell death throughout postnatal development. The remaining cells form the thin and compact cortical layer 6b (L6b) in murine cortex. The functional aspects of L6b have received little attention compared to the other layers. Recent studies have argued that the extensive intracortical connections and cortico-thalamic-cortical loops of L6b neurons might enable sensory processing to extract salien

…As a neuropeptide, orexin is crucially involved in initiating behavioral and physiological responses to threatening and unfeeling stimuli. However, the role of the orexin receptors of the NAc area after exposure to restraint stress (RS) as acute physical stress in the modulation of acute pain is unclear. The 23-gauge guide cannula was unilaterally implanted intra-NAc. The SB334867 and TCS OX2 29 were used as antagonists for OX1r and OX2r, respectively. Different doses of

An intriguing, relatively unexplored therapeutic avenue to investigate epilepsy is the interaction of sleep mechanisms and seizures. Multiple lines of clinical observations suggest a strong, bi-directional relationship between epilepsy and sleep. Epilepsy and sleep disorders are common comorbidities. Seizures occur more commonly in sleep in many types of epilepsy, and in turn, seizures can cause disrupted sleep. Sudden unexplained death in epilepsy (SUDEP) is strongly associated with sleep. The biological mechanisms underlying this relationship between seizures and sleep are poorly understood,

…lab investigates how the hypothalamic orexin (hypocretin) neurons and their downstream circuits participate in social interaction behaviours. These neurons are located exclusively in the hypothalamus that regulates complex and goal-directed behaviours. We recentl