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All parts of the brain › Brain chemicals › Orexin

Where is orexin (hypocretin) made in the brain?

Orexin, also called hypocretin, is made only in the hypothalamus: by 50,000 to 80,000 neurons in the human brain, mostly in the lateral hypothalamus and the perifornical area around the fornix. Their fibres project widely: to the rest of the hypothalamus, to the brainstem’s arousal nuclei (the locus coeruleus, raphe nuclei and ventral tegmental area among them), and to the septum, amygdala and prefrontal cortex. [1][2]

The 3D brain needs JavaScript. The lists below still say where orexin is made and where it is sent.

Lit: the parts that hold the cells making orexin (blue) and the parts it is sent to (orange).

Slice

Where orexin is made is lit in blue, where it is sent in orange. Drag to turn, pinch or scroll to zoom; tap a part or a “light” button to name it on its own; .

Not separate shapes in this atlas; lit: the parts that hold them. Lit in blue: the whole hypothalamus, which holds the lateral hypothalamus and perifornical area; the cell groups that make orexin are too small to be shapes in the BodyParts3D model, so nothing is drawn at a guessed point. [1][2]

Lit in orange: the midbrain, pons, medulla oblongata, septum (septum of telencephalon) and amygdala, where its fibres end. The fibres themselves are not drawn: the two colours show where the cells are and where they send orexin, not the routes in between. [3]

Made in: lit in blue

  • Lateral hypothalamus, lit as the hypothalamus: The outer zone of the hypothalamus holds its main orexin-making nucleus; with the perifornical area around the fornix it holds 50,000 to 80,000 orexin neurons. Neither has a shape of its own here, so the whole hypothalamus is lit. [1][2]

Sent to: lit in orange

  • Ventral tegmental area, lit as the midbrain (lateral hypothalamic group): The dopamine-making nucleus of the midbrain; not a separate shape here, so the midbrain is lit. [1][2]
  • Locus coeruleus, lit as the pons (arousal nuclei): The noradrenaline-making nucleus, strongly excited by orexin; it sits in the pons, so the pons is lit. [2][1]
  • Medulla oblongata (perifornical-dorsal group): Brainstem targets here include the solitary nucleus, the nucleus ambiguus, the dorsal nucleus of the vagus nerve and the rostral ventrolateral medulla. [2]
  • Septum (septum and Amygdala): Both its medial and lateral septal nuclei are output regions. [2]
  • Amygdala (septum and Amygdala): Its central and medial parts are output regions; the central nucleus also sends input back to the lateral hypothalamus. [2]
  • Not lit as a target: the ventromedial prefrontal cortex, which the lateral hypothalamic orexin neurons preferentially reach with the ventral tegmental area. It has no shape of its own; lighting the whole prefrontal cortex would cover the deeper targets, so it is left grey; see where it lies on the ventromedial prefrontal cortex page. [1]
  • Also reached but inside the hypothalamus, lit in blue, so not lit apart: the orexin fibres reach the whole rest of the hypothalamus, most of all its posterior part, the arcuate and paraventricular nuclei and the tuberomammillary nucleus, which makes histamine. [2]
  • Also reached but inside parts already lit in orange: the serotonin-making raphe nuclei, the acetylcholine-making pedunculopontine and laterodorsal tegmental nuclei, and the periaqueductal grey, in the midbrain and pons. [2]

The pathways, as the sources name them

  • Lateral hypothalamic group, from the orexin neurons of the lateral hypothalamus to the ventral tegmental area and the ventromedial prefrontal cortex (not lit; see above). One of the two groups the orexin neurons divide into; closely tied to reward-related functions such as learning to prefer a place. [1] See What part of the brain controls reward, pleasure and motivation?
  • Perifornical-dorsal group, from the orexin neurons around the fornix to the rest of the hypothalamus and down to the brainstem. The other group, tied to arousal and to automatic (autonomic) body functions; orexin released in the brainstem tunes breathing, blood pressure and digestion. [1][2]
  • Arousal nuclei, from the lateral hypothalamus to the histamine, dopamine, noradrenaline, serotonin and acetylcholine cell groups of the arousal system. These cell groups are the main components of the ascending reticular activating system; orexin excites them, which is how it steadies wakefulness. [2][1] See What part of the brain controls sleep?
  • Septum and Amygdala, from the lateral hypothalamus forward to the septal nuclei and the amygdala. Two of the forebrain output regions the lateral hypothalamus article lists, with the bed nucleus of the stria terminalis, the lateral habenula and the substantia innominata. [2]

Good to know

  • Two names for one system: it was found in 1998 by two groups at almost the same time. One named it orexin, from the Greek orexis, “appetite”; the other named it hypocretin, because it is made in the hypothalamus and slightly resembles the gut peptide secretin. Officially “hypocretin” (HCRT) names the gene and “orexin” the peptides. [1]
  • Two peptides and two receptors: orexin-A (33 amino acids) and orexin-B (28) are cut from one precursor and act on the OX1 and OX2 receptors; orexin-A binds both about equally, orexin-B mainly OX2. [1]
  • Waking: orexin neurons weigh up metabolic, daily-clock and sleep-debt signals to set whether an animal should be asleep or awake; they excite the dopamine, noradrenaline, histamine and acetylcholine systems and help keep both waking and sleep stable. [1] See What part of the brain controls sleep?
  • Appetite and energy: it was first thought to drive mainly eating, because orexin given into the brain increased food intake; it also raises energy expenditure, and orexin cells are switched on by ghrelin and low blood glucose and held back by leptin. [1] See What part of the brain controls hunger?

What it takes part in

Each lit with every part that takes part: What part of the brain controls sleep? · What part of the brain controls consciousness? · What part of the brain controls hunger? · What part of the brain controls reward, pleasure and motivation?

Where it is made, each on its own page: Lateral hypothalamus.

Sources

  1. Wikipedia: Orexin
  2. Wikipedia: Lateral hypothalamus
  3. BodyParts3D 4.0 (3D model measured on this page), © DBCLS, CC BY-SA 2.1 Japan

Facts describe anatomy and normal function only. The 3D model is the adult male BodyParts3D brain (credits and licence); the cell groups that make orexin have no shape in it, so the parts that hold them are lit. Real brains vary.