Hypocretins (Orexins): Twenty Years of Dissecting Arousal Circuits

  title={Hypocretins (Orexins): Twenty Years of Dissecting Arousal Circuits},
  author={Kimberly J. Jennings and Luis de Lecea},
  journal={The Orexin/Hypocretin System},
7 Citations

Orexin/Hypocretin Type 2 Receptor (HCRTR2) Gene as a Candidate Gene in Sertraline-Associated Insomnia in Depressed Patients

The findings support the idea that some variants of the HCRTR might contribute to inter-individual variability in the sleep pattern of patients receiving antidepressants.

Neurobiological and Hormonal Mechanisms Regulating Women’s Sleep

The convincing evidence for the role of ovarian hormones in regulating female sleep is discussed, and how these hormones act on a multitude of brain regions and neurochemicals to impact sleep is surveyed.

Neural and Hormonal Control of Sexual Behavior

The neural circuits of male and female sexual motivation and behavior are reviewed, from initial sensory detection of pheromones to the extended amygdala and on to medial hypothalamic nuclei and reward systems.



Hypocretin (orexin) neuromodulation of stress and reward pathways

The hypocretins/orexins: integrators of multiple physiological functions

The discovery of Hcrt/orexins and their receptors are reviewed and a hypothesis as to how the orexin system orchestrates these multifaceted physiological functions is proposed.

Arousal and reward: a dichotomy in orexin function

Arousal effect of orexin A depends on activation of the histaminergic system

  • Zhi-Li HuangW. Qu O. Hayaishi
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
Findings strongly indicate that the arousal effect of orexin A depends on the activation of histaminergic neurotransmission mediated by H1R.

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

  • J. HaganR. Leslie N. Upton
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
It is shown 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 and modulates neuroendocrine function.

Orexin/hypocretin system modulates amygdala-dependent threat learning through the locus coeruleus

It is shown that orexin acts upstream of the amygdala via the noradrenergic locus coeruleus to enable threat (fear) learning, specifically during the aversive event.

Functional wiring of hypocretin and LC-NE neurons: implications for arousal

The role of noradrenergic neurons in the brainstem locus coeruleus are found to be particularly important for mediating the effects of hypocretin neurons on arousal, and the implications of the anatomical connectivity of these neurons in regulating the arousal state of an organism across various states of sleep and wakefulness are considered.

Orexin/Hypocretin Excites the Histaminergic Neurons of the Tuberomammillary Nucleus

A functional connection between the two populations of hypothalamic neurons is suggested and that they may cooperate in the regulation of rapid-eye-movement sleep and feeding.