The
supraoptic nucleus (
SON) is a
nucleusIn neuroanatomy, a nucleus is a brain structure consisting of a relatively compact cluster of neurons. It is one of the two most common forms of nerve cell organization, the other being layered structures such as the cerebral cortex or cerebellar cortex. In anatomical sections, a nucleus shows up...
of
magnocellular neurosecretory cellMagnocellular neurosecretory cells are large cells within the supraoptic nucleus and paraventricular nucleus of the hypothalamus. They are also found in smaller numbers in accessory cell groups between these two nuclei, the largest one being the nucleus circularis...
s in the
hypothalamusThe hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the
optic chiasmThe optic chiasm or optic chiasma is the part of the brain where the optic nerves partially cross...
. In humans, it contains about 3,000 neurons.
The cell bodies produce two closely-related
peptidePeptides are short polymers formed from the linking, in a defined order, of α-amino acids. The link between one amino acid residue and the next is called an amide bond or a peptide bond....
hormoneA hormone is a chemical released by one or more cells that affects cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. It is essentially a chemical messenger that transports a signal from one cell to another. All multicellular organisms...
s:
vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a hormone found in most mammals, including humans. Vasopressin is a peptide hormone. It is derived from a preprohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the...
and
oxytocinOxytocin is a mammalian hormone that also acts as a neurotransmitter in the brain.It is best known for its roles in female reproduction: it is released in large amounts after distension of the cervix and vagina during labor, and after stimulation of the nipples, facilitating birth and...
. Every supraoptic neuron is thought to make either
oxytocinOxytocin is a mammalian hormone that also acts as a neurotransmitter in the brain.It is best known for its roles in female reproduction: it is released in large amounts after distension of the cervix and vagina during labor, and after stimulation of the nipples, facilitating birth and...
or
vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a hormone found in most mammals, including humans. Vasopressin is a peptide hormone. It is derived from a preprohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the...
, although a few make both.
In the cell bodies, the hormones are packaged in large, membrane-bound vesicles which are transported down the
axonAn axon or nerve fiber is a long, slender projectionof a nerve cell, or neuron, that conducts electrical impulsesaway from the neuron's cell body or soma....
s to the nerve endings.
The
supraoptic nucleus (
SON) is a
nucleusIn neuroanatomy, a nucleus is a brain structure consisting of a relatively compact cluster of neurons. It is one of the two most common forms of nerve cell organization, the other being layered structures such as the cerebral cortex or cerebellar cortex. In anatomical sections, a nucleus shows up...
of
magnocellular neurosecretory cellMagnocellular neurosecretory cells are large cells within the supraoptic nucleus and paraventricular nucleus of the hypothalamus. They are also found in smaller numbers in accessory cell groups between these two nuclei, the largest one being the nucleus circularis...
s in the
hypothalamusThe hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the
optic chiasmThe optic chiasm or optic chiasma is the part of the brain where the optic nerves partially cross...
. In humans, it contains about 3,000 neurons.
Function
The cell bodies produce two closely-related
peptidePeptides are short polymers formed from the linking, in a defined order, of α-amino acids. The link between one amino acid residue and the next is called an amide bond or a peptide bond....
hormoneA hormone is a chemical released by one or more cells that affects cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. It is essentially a chemical messenger that transports a signal from one cell to another. All multicellular organisms...
s:
vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a hormone found in most mammals, including humans. Vasopressin is a peptide hormone. It is derived from a preprohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the...
and
oxytocinOxytocin is a mammalian hormone that also acts as a neurotransmitter in the brain.It is best known for its roles in female reproduction: it is released in large amounts after distension of the cervix and vagina during labor, and after stimulation of the nipples, facilitating birth and...
. Every supraoptic neuron is thought to make either
oxytocinOxytocin is a mammalian hormone that also acts as a neurotransmitter in the brain.It is best known for its roles in female reproduction: it is released in large amounts after distension of the cervix and vagina during labor, and after stimulation of the nipples, facilitating birth and...
or
vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a hormone found in most mammals, including humans. Vasopressin is a peptide hormone. It is derived from a preprohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the...
, although a few make both.
In the cell bodies, the hormones are packaged in large, membrane-bound vesicles which are transported down the
axonAn axon or nerve fiber is a long, slender projectionof a nerve cell, or neuron, that conducts electrical impulsesaway from the neuron's cell body or soma....
s to the nerve endings. The secretory granules are called Herring bodies.
Similar magnocellular neurons are also found in the
paraventricular nucleusThe paraventricular nucleus is a neuronal nucleus in the hypothalamus. It contains multiple subpopulations of neurons that are activated by a variety of stressful and/or physiological changes. Many PVN neurons project directly to the posterior pituitary where they release oxytocin or vasopressin...
.
Signaling
Every (or nearly every) neuron in the nucleus has one long
axonAn axon or nerve fiber is a long, slender projectionof a nerve cell, or neuron, that conducts electrical impulsesaway from the neuron's cell body or soma....
that projects to the posterior pituitary gland, where it gives rise to about 10,000 neurosecretory nerve terminals. The magnocellular neurons are electrically excitable: In response to afferent stimuli from other neurons, they generate action potentials which propagate down the axons. When an action potential invades a neurosecretory terminal, the terminal is depolarised, and calcium enters the terminal through voltage-gated channels. The calcium entry triggers the secretion of some of the vesicles by a process known as
exocytosisExocytosis is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
. The vesicle contents are released into the extracellular space, from where they diffuse into the bloodstream.
Regulation of supraoptic neurons
Vasopressin is secreted from the pituitary gland in response to an increase in the sodium concentration of the blood (such as after a period of dehydration), or in response to a fall in the volume of the blood (such as after hemorrhage). Vasopressin acts at the kidneys to promote resorption of water (antidiuresis), producing a more concentrated urine. Vasopressin also constricts many peripheral blood vessels.
Oxytocin is secreted in large amounts during
birthChildbirth is the culmination of a human pregnancy or gestation period with birth of one or more newborn infants from a woman's uterus...
, when it causes the
uterusThe uterus is a major female hormone-responsive reproductive sex organ of most mammals, including humans. It is within the uterus that the fetus develops during gestation. The term uterus is used consistently within the medical and related professions; the Germanic term, womb is more common in...
to contract, thus assisting in expelling the fetus from the birth canal. Oxytocin secretion also plays an essential role in
lactationLactation describes the secretion of milk from the mammary glands, the process of providing that milk to the young, and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, and in humans it is commonly referred to as breastfeeding or nursing...
; oxytocin acts at the
mammary glandMammary glands are the organs that, in mammals, produce milk for the sustenance of the young. These exocrine glands are enlarged and modified sweat glands and give mammals their name...
to cause milk to be let down in response to suckling. Many other stimuli can cause the secretion of oxytocin and vasopressin, but these are thought to be the most important physiological factors.
For vasopressin and oxytocin to be secreted at appropriate times, the cell bodies must be activated by relevant stimuli. The electrical activity of supraoptic neurons is regulated by inputs from many different brain regions. Some inputs come from structures adjacent to the anterior wall of the third ventricle (the
subfornical organThe subfornical organ, situated on the ventral surface of the fornix, at the foramen of Monro, is one of the circumventricular organs of the brain.-Relations with other circumventricular organs:...
, the
organum vasculosum of the lamina terminalisThe organum vasculosum of the lamina terminalis is one of the circumventricular organs of the brain . Other circumventricular organs are the subfornical organ and the area postrema in the brainstem.-AV3V region:...
, and the nucleus medianus); these provide information relevant for the regulation of body fluid and electrolyte homeostasis, in which the secretion of
vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a hormone found in most mammals, including humans. Vasopressin is a peptide hormone. It is derived from a preprohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the...
plays a particularly important role.
Some other inputs come from the brainstem, including from some of the noradrenergic neurons of the nucleus of the solitary tract and the ventrolateral medulla. However many of the direct inputs to the supraoptic nucleus come from neurons just outside the nucleus (the "perinuclear zone"). Oxytocin neurons respond to stimulation of the nipples (resulting in milk let-down) and in response to uterine contractions and distension of the birth canal (the "Ferguson reflex"), but the pathways by which these stimuli reach the neurons are not fully known.
Of the afferent inputs to the supraoptic nucleus, most contain either the inhibitory neurotransmitter
GABAGabâ or gabaa, for the Cebuano people , is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
or the excitatory neurotransmitter glutamate, but these transmitters often co-exist with various peptides. Other afferent neurotransmitters include noradrenaline (from the brainstem), dopamine, serotonin and acetylcholine.
The supraoptic nucleus as a "model system"
The supraoptic nucleus is an important "model system" in neuroscience. There are many reasons for this: some technical advantages of working on the supraoptic nucleus are that the cell bodies are relatively large, the cells make exceptionally large amounts of their secretory products, and the nucleus is relatively homogeneous and easy to separate from other brain regions. The gene expression and electrical activity of supraoptic neurons has been studied extensively, in many physiological and experimental conditions. These studies have led to many insights of general importance, as in the examples below.
Morphological plasticity in the supraoptic nucleus
Anatomical studies using electron microscopy have shown that the morphology of the supraoptic nucleus is remarkably adaptable.
For example, during
lactationLactation describes the secretion of milk from the mammary glands, the process of providing that milk to the young, and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, and in humans it is commonly referred to as breastfeeding or nursing...
there are large changes in the size and shape of the oxytocin neurons, in the numbers and types of synapses that these neurons receive, and in the structural relationships between neurons and glial cells in the nucleus. These changes arise during parturition, and are thought to be important adaptations that prepare the oxytocin neurons for a sustained high demand for oxytocin. Oxytocin is essential for milk let-down in response to suckling.
These studies showed that the brain was much more "plastic" in its anatomy than previously recognized, and led to great interest in the interactions between glial cells and neurons generally.
Pulsatile hormone secretion
In 1973, Jonathan Wakerley was a graduate student working in Bristol under the supervision of Dennis Lincoln. In a series of elegant experiments, Wakerley showed the behavior of oxytocin neurons in response to the suckling stimulus. By recording the electrical activity of single neurons in the supraoptic nucleus of anesthetised rats, he showed that, in response to suckling, the oxytocin neurons discharge action potentials in brief intense synchronised bursts. These bursts occurred every few minutes while the pups were suckling at the nipples, and each burst caused the release of a large pulse of oxytocin into the blood that resulted in a large rise in intramammary pressure, reflecting acute milk let-down. Similar bursts of electrical activity occur during parturition, associated with each birth.
The importance of these experiments was in showing that the role of the hypothalamus was to produce a patterned response to the continuous stimulus of suckling. For oxytocin to be effective in causing milk let down, it is important that it is released in large, discrete pulses - if oxytocin is delivered continuously rather than in pulses, the mammary gland rapidly desensitises.
Before these experiments, it was often assumed that the concentrations of circulating hormones change relatively slowly. These experiments prompted researchers to study the temporal pattern of hormone secretion much more closely. They found that many hormones, including most of the hormones secreted from the
anterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
gland, are also released in pulses, and that these pulsatile patterns are very important for the biological efficacy of the hormonal signals.
Stimulus-secretion coupling
In response to, for instance, a rise in the plasma sodium concentration, vasopressin neurons also discharge action potentials in bursts, but these bursts are much longer and are less intense than the bursts displayed by oxytocin neurons, and the bursts in vasopressin cells are not synchronised .
It seemed strange that the vasopressin cells should fire in bursts. As the activity of the vasopressin cells is not synchronised, the overall level of vasopressin secretion into the blood is continuous, not pulsatile. Richard Dyball and his co-workers speculated that this pattern of activity, called "phasic firing", might be particularly effective for causing vasopressin secretion. They showed this to be the case by studying vasopressin secretion from the isolated posterior pituitary gland in vitro. They found that vasopressin secretion could be evoked by electrical stimulus pulses applied to the gland, and that much more hormone was released by a phasic pattern of stimulation than by a continuous pattern of stimulation.
These experiments led to interest in "stimulus-secretion coupling" - the relationship between electrical activity and secretion. Supraoptic neurons are unusual because of the large amounts of peptide that they secrete, and because they secrete the peptides into the blood. However many neurons in the brain, and especially in the hypothalamus, synthesize peptides. It is now thought that bursts of electrical activity might be generally important for releasing large amounts of peptide from peptide-secreting neurons.
Dendritic secretion
Supraoptic neurons have typically 1-3 large dendrites, most of which project ventrally to form a mat of process at the base of the nucleus, called the
ventral glial lamina. The dendrites receive most of the synaptic terminals from afferent neurons that regulate the supraoptic neurons, but neuronal dendrites are often actively involved in information processing, rather than being simply passive receivers of information. The dendrites of supraoptic neurons contain large numbers of neurosecretory vesicles that contain oxytocin and vasopressin, and they can be released from the dendrites by exocytosis. The oxytocin and vasopressin that is released at the posterior pituitary gland enters the blood, and cannot re-enter the brain because the
blood-brain barrierThe blood-brain barrier is a separation of circulating blood and cerebrospinal fluid maintained by the choroid plexus in the central nervous system . Endothelial cells restrict the diffusion of microscopic objects The blood-brain barrier (BBB) is a separation of circulating blood and...
does not allow oxytocin and vasopressin through, but the oxytocin and vasopressin that is released from dendrites acts within the brain. Oxytocin neurons themselves express oxytocin receptors, and vasopressin neurons express vasopressin receptors, so dendritically-released peptides "autoregulate" the supraoptic neurons. Francoise Moos and Phillipe Richard first showed that the autoregulatory action of oxytocin is important for the milk-ejection reflex.
These peptides have relatively long half-lives in the brain (about 20 minutes in the CSF), and they are released in large amounts in the supraoptic nucleus, and so they are available to diffuse through the extracellular spaces of the brain to act at distant targets. Oxytocin and vasopressin receptors are present in many other brain regions, including the
amygdalaThe ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans...
, brainstem,
septumIn anatomy, a septum is a wall, dividing a cavity or structure into smaller ones.- In human anatomy :* Interatrial septum, the wall of tissue that separates the left and right atria of the heart...
, and most other nuclei in the hypothalamus.
Because so much vasopressin and oxytocin are released at this site, studies of the supraoptic nucleus have made an important contribution to understanding how release from dendrites is regulated, and in understanding its physiological significance.
Co-existing peptides
Vasopressin neurons and oxytocin make many other neuroactive substances in addition to vasopressin and oxytocin, though most are present only in small quantities. However, some of these other substances are known to be important.
DynorphinDynorphins are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 , multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neo-endorphin...
produced by vasopressin neurons is involved in regulating the phasic discharge patterning of vasopressin neurons, and
nitric oxideNitric oxide or nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of mammals, including humans, and is an extremely important intermediate in the chemical industry...
produced by both neuronal types is a negative-feedback regulator of cell activity. Oxytocin neurons also make dynorphin; in these neurons, dynorphin acts at the nerve terminals in the posterior pituitary as a negative feedback inhibitor of oxytocin secretion. Oxytocin neurons also make large amounts of
cholecystokininCholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein...
and cocaine-and amphetamine regulatory transcript (CART).