The subfornical organ (SFO) is one of the
circumventricular organs
Circumventricular organs (CVOs) ( circum-: around ; ventricular: of ventricle) are structures in the brain characterized by their extensive and highly permeable capillaries, unlike those in the rest of the brain where there exists a blood ...
of the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
.
Its name comes from its location on the ventral surface of the
fornix near the
interventricular foramina (foramina of Monro), which interconnect the
lateral ventricles
The lateral ventricles are the two largest ventricles of the brain and contain cerebrospinal fluid (CSF). Each cerebral hemisphere contains a lateral ventricle, known as the left or right ventricle, respectively.
Each lateral ventricle resemble ...
and the
third ventricle
The third ventricle is one of the four connected ventricles of the ventricular system within the mammalian brain. It is a slit-like cavity formed in the diencephalon between the two thalami, in the midline between the right and left lateral v ...
. Like all circumventricular organs, the subfornical organ is well-vascularized, and like all circumventricular organs except the
subcommissural organ
The subcommissural organ (SCO) is one of the circumventricular organs of the brain. It is a small glandular structure that is located in the posterior region of the third ventricle, near the entrance of the cerebral aqueduct. The name of the SC ...
, some SFO
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: ...
have
fenestra
A fenestra (fenestration; plural fenestrae or fenestrations) is any small opening or pore, commonly used as a term in the biological sciences. It is the Latin word for "window", and is used in various fields to describe a pore in an anatomical st ...
tions, which increase capillary permeability.
The SFO is considered a sensory circumventricular organ because it is responsive to a wide variety of hormones
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and beh ...
and neurotransmitters
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neur ...
, as opposed to secretory circumventricular organs, which are specialized in the release of certain substances.
Anatomy
As noted above, capillaries in some subregions within the SFO are fenestrated, and thus lack a blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
. All circumventricular organs except the subcommissural organ contain fenestrated capillaries, a feature that distinguishes them from most other parts of the brain. The SFO can be divided into six anatomical zones based on its capillary
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: ...
topography
Topography is the study of the forms and features of land surfaces. The topography of an area may refer to the land forms and features themselves, or a description or depiction in maps.
Topography is a field of geoscience and planetary sci ...
: two zones in the coronal plane
The coronal plane (also known as the frontal plane) is an anatomical plane that divides the body into dorsal and ventral sections. It is perpendicular to the sagittal and transverse planes.
Details
The coronal plane is an example of a longitud ...
and four zones in the sagittal plane
The sagittal plane (; also known as the longitudinal plane) is an anatomical plane that divides the body into right and left sections. It is perpendicular to the transverse and coronal planes. The plane may be in the center of the body and divid ...
.[ The central zone is composed of the ]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 mye ...
, neuronal cell bodies and a high density of fenestrated capillaries. Conversely, the rostral and caudal areas have a lower density of capillaries[ and are mostly made of nerve fibers, with fewer neurons and glial cells seen in this area. Functionally, however, the SFO may be viewed in two portions, the dorsolateral peripheral division, and the ventromedial core segment.]
The subfornical organ contains endothelin
Endothelins are peptides with receptor (biochemistry), receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when gene ex ...
receptors mediating vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessel ...
and high rates of glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
metabolism mediated by calcium channel
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels.
Comparison tables
The following tables e ...
s.
General function
The subfornical organ is active in many bodily processes,[ including ]osmoregulation
Osmoregulation is the active regulation of the osmotic pressure of an organism's body fluids, detected by osmoreceptors, to maintain the homeostasis of the organism's water content; that is, it maintains the fluid balance and the concentration o ...
, cardiovascular regulation, and energy homeostasis.[ Most of these processes involve ]fluid balance
Fluid balance is an aspect of the homeostasis of organisms in which the amount of water in the organism needs to be controlled, via osmoregulation and behavior, such that the concentrations of electrolytes (salts in solution) in the various body ...
through the control of the release of certain hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s, particularly angiotensin
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrena ...
or vasopressin
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
.[
]
Cardiovascular regulation
The impact of the SFO on the cardiovascular system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
is mostly mediated through its influence on fluid balance
Fluid balance is an aspect of the homeostasis of organisms in which the amount of water in the organism needs to be controlled, via osmoregulation and behavior, such that the concentrations of electrolytes (salts in solution) in the various body ...
.[ The SFO plays a role in ]vasopressin
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
regulation. Vasopressin is a hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
that, when bound to receptors in the kidneys
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
, increases water retention by decreasing the amount of fluid transferred from blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
to urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra.
Cel ...
by the kidneys. This regulation of blood volume
Blood volume (volemia) is the volume of blood (blood cells and plasma) in the circulatory system of any individual.
Humans
A typical adult has a blood volume of approximately 5 liters, with females and males having approximately the same blood per ...
affects other aspects of the cardiovascular system. Increased or decreased blood volume influences blood pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
, which is regulated by baroreceptors
Baroreceptors (or archaically, pressoreceptors) are sensors located in the carotid sinus (at the bifurcation of external and internal carotids) and in the aortic arch. They sense the blood pressure and relay the information to the brain, so that a ...
, and can in turn affect the strength of ventricular contraction in the heart
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
. Additional research has demonstrated that the subfornical organ may be an important intermediary through which leptin
Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate Energy homeostasis, energy balance by inhib ...
acts to maintain blood pressure within normal physiological limits via descending autonomic pathways associated with cardiovascular control.[
SFO neurons have also been experimentally shown to send ]efferent
Efferent may refer to:
Anatomical structures
Meaning 'conveying away from a center':
*Efferent arterioles, conveying blood away from the Bowman's capsule in the kidney
*Efferent nerve fiber, carries nerve impulses away from the central nervous sy ...
projections to regions involved in cardiovascular regulation including the lateral 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 ...
, with fibers terminating in the supraoptic (SON) and paraventricular (PVN) nuclei, and the anteroventral 3rd ventricle (AV3V) with fibers terminating in the OVLT and the median preoptic area.[
]
Relationship with other circumventricular organs
Other circumventricular organs participating in systemic regulatory processes are the area postrema
The area postrema, a paired structure in the medulla oblongata of the brainstem, is a circumventricular organ having permeable capillaries and sensory neurons that enable its dual role to detect circulating chemical messengers in the blood and ...
and the OVLT.[ The OVLT and SFO are both interconnected with the nucleus medianus, and together these three structures comprise the so-called "AV3V" region – the region anterior and ventral to the ]third ventricle
The third ventricle is one of the four connected ventricles of the ventricular system within the mammalian brain. It is a slit-like cavity formed in the diencephalon between the two thalami, in the midline between the right and left lateral v ...
.[ The AV3V region is important in the regulation of fluid and electrolyte balance, by controlling ]thirst
Thirst is the craving for potable fluids, resulting in the basic instinct of animals to drink. It is an essential mechanism involved in fluid balance. It arises from a lack of fluids or an increase in the concentration of certain osmolites, suc ...
, sodium excretion, blood volume regulation, and vasopressin
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
secretion.[ The SFO, area postrema, and OVLT have capillaries permeable to circulating hormonal signals, enabling these three circumventricular organs to have integrative roles in cardiovascular, electrolyte, and fluid regulation.][
]
Hormones and receptors
Neurons
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. N ...
in the subfornical organ have receptors for many hormones
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and beh ...
that circulate in the blood but which do not cross the blood–brain barrier,[ including ]angiotensin
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrena ...
, atrial natriuretic peptide
Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/pa ...
, endothelin
Endothelins are peptides with receptor (biochemistry), receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when gene ex ...
and relaxin
Relaxin is a protein hormone of about 6000 Da first described in 1926 by Frederick Hisaw.
The relaxin family peptide hormones belong to the insulin superfamily and consists of seven peptides of high structural but low sequence similarity; rela ...
. The role of the SFO in angiotensin regulation is particularly important, as it is involved in communication with the nucleus medianus (also called the median preoptic nucleus). Some neurons in the SFO are osmoreceptor
An osmoreceptor is a sensory receptor primarily found in the hypothalamus of most homeothermic organisms that detects changes in osmotic pressure. Osmoreceptors can be found in several structures, including two of the circumventricular organs – t ...
s, being sensitive to the osmotic pressure
Osmotic pressure is the minimum pressure which needs to be applied to a solution to prevent the inward flow of its pure solvent across a semipermeable membrane.
It is also defined as the measure of the tendency of a solution to take in a pure ...
of the blood. These neurons project to the supraoptic nucleus
The supraoptic nucleus (SON) is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm. In humans, the SON contains about 3,000 ne ...
and paraventricular nucleus
The paraventricular nucleus (PVN, PVA, or PVH) is a nucleus in the hypothalamus. Anatomically, it is adjacent to the third ventricle and many of its neurons project to the posterior pituitary. These projecting neurons secrete oxytocin and a smaller ...
to regulate the activity of vasopressin
Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...
-secreting neurons. These neurons also project to the nucleus medianus which is involved in controlling thirst
Thirst is the craving for potable fluids, resulting in the basic instinct of animals to drink. It is an essential mechanism involved in fluid balance. It arises from a lack of fluids or an increase in the concentration of certain osmolites, suc ...
. Thus, the subfornical organ is involved in fluid balance
Fluid balance is an aspect of the homeostasis of organisms in which the amount of water in the organism needs to be controlled, via osmoregulation and behavior, such that the concentrations of electrolytes (salts in solution) in the various body ...
.
Other important hormones have been shown to excite the SFO, specifically serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
, carbamylcholine (carbachol), and atropine
Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...
. These neurotransmitters
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neur ...
however seem to have an effect on deeper areas of the SFO than angiotensin, and antagonist
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
s of these hormones have been shown to also primarily effect the non-superficial regions of the SFO (other than atropine antagonists, which showed little effects). In this context, the superficial region is considered to be 15-55μm deep into the SFO, and the "deep" region anything below that.
From these reactions to certain hormones and other molecules, a model of the neuronal organization of the SFO is suggested in which angiotensin-sensitive neurons lying superficially are excited by substances borne by blood or cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
, and synapse
In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell.
Synapses are essential to the transmission of nervous impulses from ...
with deeper carbachol-sensitive neurons. The axons
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, th ...
of these deep neurons pass out of the SFO in the columns and body of the fornix. Afferent fibers from the body and columns of the fornix polysynaptically excite both superficial and deep neurons. A recurrent inhibitory
An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Incorporated; 2008. ...
circuit is suggested on the output path.[
]
Genetics
The expression of various genes
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
in the subfornical organ have been studied. For example, it was seen that water deprivation in rats led to an upregulation
In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary proce ...
of the mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
that codes for angiotensin II receptors, allowing for a lower angiotensin concentration in the blood that produce the "thirst" response. It also has been observed to be a site of thyroid
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
transcription factor 1 (TTF1) production, a protein generally produced in the 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 ...
.
Pathology
Hypertension
Hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, or high blood pressure, is highly affected by the concentration of angiotensin. Injection of angiontensin has actually been long used to induce hypertension in animal test models to study the effects of various therapies and medications. In such experiments, it has been observed that an intact and functioning subfornical organ limits the increase in mean arterial pressure due to the increased angiotensin.
Dehydration
As stated above, angiotensin
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrena ...
receptors (AT1) have been shown to be upregulated due to water deprivation. These AT1 receptors have also shown an increased bonding with circulating angiotensin after water deprivation. These findings could indicate some sort of morphological change in the AT1 receptor, likely due to some signal protein modification of the AT1 receptor at a non-bonding site, leading to an increased affinity of the AT1 receptor for angiotensin bonding.
Research
Feeding
Although generally viewed primarily as having roles in homeostasis
In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...
and cardiovascular regulation, the subfornical organ has been thought to control feeding patterns through taking inputs from the blood (various peptides
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A p ...
indicating satiety
Satiety ( ) is a state or condition of fullness gratified beyond the point of satisfaction, the opposite of hunger. It is a state which induces meal termination.Hetherington, M.Sensory-specific satiety and its importance in meal termination ''Neuro ...
) and then stimulating hunger. It has been shown to induce drinking in rat
Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' ( pack rats), ''Bandicota'' (bandicoot ...
s as well as eating.[
]
References
{{Authority control
Ventricular system
Neuroendocrinology