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All parts of the brain › Brain chemicals › Neuropeptide Y

Where is neuropeptide Y (NPY) made in the brain, and where is it sent?

Neuropeptide Y (NPY) is made mostly in the arcuate nucleus at the base of the hypothalamus, one of the brain’s richest NPY sites, and also by C1 nerve cells in the medulla oblongata and by interneurons in the hippocampus. [1][2][3]

The hypothalamus, the medulla oblongata and the hippocampus lit in blue and the amygdala, the caudate nucleus and the putamen lit in orange on a 3D model of the brain, seen from the front left and below

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

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Where neuropeptide Y 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; .

The arcuate’s NPY/AgRP neurons, which raise appetite, send it to the paraventricular nucleus and the lateral hypothalamus, inside the same lit hypothalamus; a review counts about 36% of the NPY nerve endings in the paraventricular nucleus as theirs and most of the rest as coming from the brainstem. NPY is a peptide 36 amino acids long. [1][2][3]

Not separate shapes in this atlas; lit: the parts that hold them. Lit in blue: the whole hypothalamus, medulla oblongata and hippocampus, which hold the arcuate nucleus, NPY-expressing C1 adrenergic neurons and NPY interneurons; the cell groups that make neuropeptide Y are too small to be shapes in the BodyParts3D model, so nothing is drawn at a guessed point. [2][1][3][4][5]

Lit in orange: the amygdala, caudate nucleus and putamen, where the cited source says NPY neurons act on reward and emotion pathways (its main hypothalamic targets lie inside the hypothalamus, already lit in blue, and are listed under “Sent to”). The fibres themselves are not drawn: the two colours show where the cells are and where they send neuropeptide Y, not the routes in between. [6]

Made in: lit in blue

  • Arcuate nucleus, lit as the hypothalamus: Its medial (inner) neurons make NPY together with AgRP and GABA and use it to raise appetite; ghrelin switches them on, and leptin, insulin and peptide YY hold them back. The source counts it among the places with the highest NPY levels. The nucleus has no shape of its own here, so the whole hypothalamus is lit. [2][1]
  • C1 cell group, in the medulla oblongata: The C1 neurons of the ventrolateral medulla express several neuropeptides, NPY among them; the review names the lower brainstem, particularly the C1 group, as the main source of the NPY nerve endings in the paraventricular nucleus. The cells have no shape here, so the medulla is lit. [3][4]
  • Hippocampus, lit as the hippocampus: High levels of NPY are made and act in the hypothalamus and the hippocampus. In the hippocampus it is made by GABA-releasing interneurons, local cells that connect neighbouring neurons; in the dentate gyrus, NPY released by interneurons supports the growth of new cells, and removing it cut that growth. [1][5]

Sent to: lit in orange

  • Amygdala (reward and emotion circuits): The source places NPY’s Y1 and Y5 receptors here, and names it, with the nucleus accumbens, as where NPY neurons interact with the brain’s dopamine reward and emotion pathways. [1]
  • Nucleus accumbens, lit as the caudate nucleus and putamen (reward and emotion circuits): Named with the amygdala as where NPY neurons interact with the dopamine reward pathways. It is not a separate shape here, so the caudate nucleus and putamen that hold it are lit. [1]

Also sent to, inside a part already lit in blue

  • Paraventricular nucleus, inside the hypothalamus, already lit in blue (arcuate and brainstem → PVN): Its NPY nerve endings come from three sources: about 42% from adrenaline-making neurons (mainly C1, plus C3), 21% from noradrenaline-making neurons and the remaining 36% from the AgRP neurons of the arcuate nucleus. NPY released there with GABA by the arcuate endings appears to raise food intake. [3][1]
  • Lateral hypothalamus, inside the hypothalamus, already lit in blue (arcuate → lateral hypothalamus): The arcuate’s NPY/AgRP/GABA neurons, in the most ventromedial part of the nucleus, project strongly to the lateral hypothalamus as well as to the paraventricular nucleus. [2]
  • Also reached but inside the part already lit in blue: the arcuate’s NPY neurons directly contact and hold back their POMC/CART neighbours, and NPY regulates those cells’ release of beta-endorphin. [2]
  • Not lit: the body’s sympathetic nerves, outside the brain. In the autonomic nervous system NPY is made mainly by sympathetic neurons, and there it is a strong constrictor of blood vessels. [1]

The pathways, as the sources name them

  • Arcuate and brainstem → PVN, from the arcuate nucleus and the brainstem’s C1 and C3 cell groups to the paraventricular nucleus of the hypothalamus. NPY or noradrenaline put into the paraventricular nucleus raises feeding, and NPY there selectively raises carbohydrate intake; NPY placed there also releases corticotropin-releasing hormone, the first step of the stress-hormone chain. [3][1] See What part of the brain controls hunger?
  • Arcuate → lateral hypothalamus, from the ventromedial part of the arcuate nucleus to the lateral hypothalamus. The same neurons are held back by leptin, insulin and peptide YY and switched on by ghrelin; when activated, they can produce ravenous eating. [2] See What part of the brain controls hunger?
  • Reward and emotion circuits, from NPY neurons the source does not place, to the amygdala and the nucleus accumbens. The source calls NPY a calming (anxiolytic) peptide the body makes itself, whose levels can be changed by stress. [1] See What part of the brain controls the stress response?

Good to know

  • NPY is a peptide 36 amino acids long; it was first isolated in 1982, from pig (porcine) hypothalamus. [1]
  • It acts through its own receptors, mainly Y1, Y2, Y4 and Y6; Y1 and Y5 are linked to raising food intake, Y2 and Y4 to holding appetite back. [1] See What part of the brain controls hunger?
  • All known NPY receptors are coupled to Gi/o proteins, so NPY is assumed to inhibit the cells it reaches; any excitatory effect of NPY is thought to come through disinhibition. [3]
  • The roles the source lists include increasing food intake and the storage of energy as fat, reducing pain perception and affecting the daily (circadian) rhythm. [1]
  • In the arcuate nucleus NPY also takes part in the growth-hormone system: GHRH neurons help control growth hormone release together with somatostatin and NPY. [2] See What part of the brain controls hormones?

What it takes part in

Each lit with every part that takes part: What part of the brain controls hunger? · What part of the brain controls the stress response? · What part of the brain controls hormones?

Where it is made, each on its own page: Arcuate nucleus; C1 cell group, in the medulla oblongata; Hippocampus.

Sources

  1. Wikipedia: Neuropeptide Y
  2. Wikipedia: Arcuate nucleus (hypothalamus)
  3. Guyenet et al. 2013, American Journal of Physiology: C1 neurons: the body’s EMTs (free full text in PMC)
  4. Wikipedia: Adrenergic cell group C1
  5. Wikipedia: Interneuron
  6. 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 neuropeptide Y have no shape in it, so the parts that hold them are lit. Real brains vary.