The arcuate nucleus of the hypothalamus (also known as ARH,
ARC,
or infundibular nucleus
) is an aggregation of
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
s in the mediobasal
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
, adjacent to the
third ventricle and the
median eminence
The median eminence, part of the inferior boundary of the hypothalamus in the brain, is attached to the infundibulum. The median eminence is a small swelling on the tuber cinereum, posterior to and atop the pituitary stalk; it lies in the area rou ...
. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and
astrocyte
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of e ...
s. The populations of neurons found in the arcuate nucleus are based on the
hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the
pituitary gland
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...
or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region.
The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in
homeostasis
In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.
Cell populations
Neuroendocrine neurons
Different groups of arcuate nucleus neuroendocrine neurons secrete various types or combinations of
neurotransmitters and
neuropeptides, such as
neuropeptide Y (NPY),
gonadotropin-releasing hormone (GnRH),
agouti-related peptide
Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nu ...
(AgRP),
cocaine- and amphetamine-regulated transcript (CART),
kisspeptin
Kisspeptins (including kisspeptin-54 (KP-54), formerly known as metastin) are proteins encoded by the ''KISS1'' gene in humans. Kisspeptins are ligands of the G-protein coupled receptor, GPR54. ''Kiss1'' was originally identified as a human me ...
,
dopamine,
substance P
Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its clo ...
,
growth hormone–releasing hormone (GHRH),
neurokinin B
Neurokinin B (NKB) belongs in the family of tachykinin peptides. Neurokinin B is implicated in a variety of human functions and pathways such as the secretion of gonadotropin-releasing hormone.
Additionally, NKB is associated with pregnancy in fem ...
(NKB),
β-endorphin,
melanocyte-stimulating hormone (MSH), and
somatostatin.
Proopiomelanocortin (POMC) is a precursor
polypeptide that is cleaved into MSH, ACTH, and β-endorphin and expressed in the arcuate nucleus.
Groups of
neuroendocrine
Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bri ...
neurons include:
* TIDA neurons, or
tuberoinfundibular dopamine neurons, are neurons that regulate the secretion of
prolactin from the pituitary gland and release the neurotransmitter
dopamine. TIDA neurons have nerve endings in the
median eminence
The median eminence, part of the inferior boundary of the hypothalamus in the brain, is attached to the infundibulum. The median eminence is a small swelling on the tuber cinereum, posterior to and atop the pituitary stalk; it lies in the area rou ...
that release
dopamine into the
hypophysial portal blood.
In lactating females, TIDA neurons are inhibited by the stimulus of suckling. Dopamine released from their nerve endings at the median eminence is transported to the
anterior pituitary gland, where it regulates the secretion of
prolactin. Dopamine inhibits prolactin secretion, so when the TIDA neurons are inhibited, there is increased secretion of prolactin, which stimulates
lactogenesis (milk production). Prolactin acts in a short-loop negative feedback manner to decrease its levels by stimulating the release of dopamine. Dopaminergic neurons of the arcuate also inhibit the release of
gonadotropin-releasing hormone, explaining in part why lactating (or otherwise
hyperprolactinemic) women experience oligomenorrhea or amenorrhea (infrequency or absence of menses).
*
Kisspeptin/NKB neurons within the arcuate nucleus form synaptic inputs with TIDA neurons. These neurons express
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...
s and also coexpress neurokinin B in female rats.
* GHRH neurons help to control
growth hormone (GH) secretion in conjunction with somatostatin and NPY.
* NPY/AgRP neurons and POMC/CART neurons make up two groups of neurons in the arcuate nucleus that are centrally involved in the neuroendocrine function of feeding. Medial neurons utilize NPY peptides as neurotransmitters to stimulate appetite, and lateral neurons utilize POMC/CART to inhibit appetite.
NPY and POMC/CART neurons are sensitive to peripheral hormones such as leptin and insulin.
POMC/CART neurons also secrete
melanocyte-stimulating hormone, which suppresses appetite.
* GnRH neurons have also been found.
These neurons secrete GnRH and
histamine.
* There are also groups of neurons expressing NKB and
dynorphin
Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin ...
that help to control reproduction.
Centrally-projecting neurons
Other types of neurons have projection pathways from the arcuate nucleus to mediate different regions of the hypothalamus or to other regions outside of the hypothalamus.
Projections of these neurons extend a long distance from the arcuate nucleus to the median eminence to influence the release of hormones from the pituitary gland.
Neurons of the arcuate nucleus have intrahypothalamic projections for neuroendocrine circuitry.
such as neural projections that influence feeding behavior project to the
paraventricular nucleus of the hypothalamus (PVH), the
dorsomedial hypothalamic nucleus
The dorsomedial hypothalamic nucleus is a nucleus of the hypothalamus. It is involved in feeding, drinking, body-weight regulation and circadian activity. More specifically, it is a necessary component for the expression of numerous behavioral a ...
(DMH, and the
lateral hypothalamic area (LHA).
Populations of neurons connect to the intermediate lobes of the pituitary gland, from the lateral division of the ARH to the neural and intermediate parts of the pituitary gland, and the caudal division of ARH to the median eminence.
Groups of neurons that project elsewhere within the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
include:
* Centrally projecting neurons that contain
neuropeptide Y (NPY),
agouti-related protein (AGRP), and the inhibitory neurotransmitter
GABA. These neurons, in the most ventromedial part of the nucleus, project strongly to the
lateral hypothalamus and to the
paraventricular nucleus of the hypothalamus, and are important in the regulation of
appetite. When activated, these neurons can produce ravenous eating. These neurons are inhibited by
leptin,
insulin, and
peptide YY
Peptide YY (PYY) also known as peptide tyrosine tyrosine is a peptide that in humans is encoded by the gene. Peptide YY is a short (36-amino acid) peptide released from cells in the ileum and colon in response to feeding. In the blood, gut, a ...
and activated by
ghrelin.
* Centrally projecting neurons that contain
peptide products of
pro-opiomelanocortin (POMC), and
cocaine- and amphetamine-regulated transcript (CART). These neurons have widespread projections to many brain areas, including to all nuclei in the hypothalamus. These cells are important in the regulation of
appetite, and, when activated, they inhibit feeding. These neurons are activated by circulating concentrations of
leptin and
insulin, and they are directly innervated and inhibited by the NPY neurons.
POMC neurons that project to the medial preoptic nucleus are also involved in the regulation of
sexual behavior
Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their sexuality. People engage in a variety of sexual acts, ranging from activities done alone (e.g., masturbation) t ...
in both males and females. The expression of POMC is regulated by gonadal steroids. The release of a POMC product, beta-endorphin is regulated by NPY.
* Centrally projecting neurons that make somatostatin; the neurosecretory somatostatin neurons that regulate growth hormone secretion are a different population, located in the periventricular nucleus.
* Feeding regulatory neurons also activate oxytocin-containing neurons of the
periventricular nucleus
The periventricular nucleus is a thin sheet of small neurons located in the wall of the third ventricle, a composite structure of the hypothalamus. It functions in analgesia.
It is located in the rostral, intermediate, and caudal regions of t ...
(PVN), which projects to nucleus of
tractus solitarius in the
medulla oblongata.
* Others receive direct synaptic inputs from extra hypothalamic sites projecting into the
amygdala, the
hippocampus, and the
entorhinal cortex.
Other neurons
Other cell populations include:
* A small population of neurons that sensitive to
ghrelin. The role of this population is not known; many neurons in the arcuate nucleus express receptors for ghrelin, but these are thought to respond mainly to blood-borne ghrelin.
* The arcuate nucleus also contains a population of specialized
ependymal cells, called
tanycytes
Tanycytes are special ependymal cells found in the third ventricle of the brain, and on the floor of the fourth ventricle and have processes extending deep into the hypothalamus. It is possible that their function is to transfer chemical signals ...
.
* Astrocytes in the arcuate nucleus hold high capacity glucose transporters that function as nutrient sensors for appetite controlling neurons
* The diverse and specialized collections of neurons reside within a special compartment with
glial cells
Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...
and have their own network of
capillaries
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
and a membrane of
tanycyte
Tanycytes are special ependymal cells found in the third ventricle of the brain, and on the floor of the fourth ventricle and have processes extending deep into the hypothalamus. It is possible that their function is to transfer chemical signals ...
s that help create a blood brain barrier.
Circulating or molecules such as hormones travel in the blood and can directly affect these neurons and their plasticity as evidence by adult neurogenesis.
References
Footnotes
*
*
*
{{DEFAULTSORT:Arcuate Nucleus
Hypothalamus
Neuroendocrinology
Human female endocrine system