Subfornical organ

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Subfornical organ
Gray715.png
Medial aspect of a brain sectioned in the median sagittal plane. (Subfornical organ not labeled, but fornix and foramen of Monro are both labeled near the center.)
Details
Identifiers
Latin organum subfornicale
MeSH D013356
NeuroLex ID nlx_anat_100314
TA98 A14.1.08.412
A14.1.09.449
TA2 5782
FMA 75260
Anatomical terms of neuroanatomy

The subfornical organ (SFO) is one of the circumventricular organs of the brain. [1] [2] 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 and the third ventricle. Like all circumventricular organs, the subfornical organ is well-vascularized, and like all circumventricular organs except the subcommissural organ, some SFO capillaries have fenestrations, which increase capillary permeability. [1] [3] [4] The SFO is considered a sensory circumventricular organ because it is responsive to a wide variety of hormones and neurotransmitters, as opposed to secretory circumventricular organs, which are specialized in the release of certain substances. [1] [4] [5]

Contents

Anatomy

Subfornical organ of a mouse. In this photomicrograph, the subfornical organ (arrow) is located on the undersurface of the fornix in the upper part of the third ventricle. The cells in this coronal section of the brain were colored with a bluish dye ("Nissl stain"). The thalamus is at the bottom of the photo. The bar at the lower right represents a distance of 200 mm (0.2mm). Subfornical organ of a mouse.jpg
Subfornical organ of a mouse. In this photomicrograph, the subfornical organ (arrow) is located on the undersurface of the fornix in the upper part of the third ventricle. The cells in this coronal section of the brain were colored with a bluish dye ("Nissl stain"). The thalamus is at the bottom of the photo. The bar at the lower right represents a distance of 200 μm (0.2mm).

As noted above, capillaries in some subregions within the SFO are fenestrated, [6] and thus lack a blood–brain barrier. All circumventricular organs except the subcommissural organ contain fenestrated capillaries, [2] a feature that distinguishes them from most other parts of the brain. [7] The SFO can be divided into six anatomical zones based on its capillary topography: two zones in the coronal plane and four zones in the sagittal plane. [3] The central zone is composed of the glial cells, neuronal cell bodies and a high density of fenestrated capillaries. [8] Conversely, the rostral and caudal areas have a lower density of capillaries [8] 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. [9]

The subfornical organ contains endothelin receptors mediating vasoconstriction and high rates of glucose metabolism mediated by calcium channels. [10]

General function

The subfornical organ is active in many bodily processes, [1] [5] including osmoregulation, [9] cardiovascular regulation, [9] and energy homeostasis. [1] [5] Most of these processes involve fluid balance through the control of the release of certain hormones, particularly angiotensin or vasopressin. [5]

Cardiovascular regulation

The impact of the SFO on the cardiovascular system is mostly mediated through its influence on fluid balance. [1] The SFO plays a role in vasopressin regulation. Vasopressin is a hormone that, when bound to receptors in the kidneys, increases water retention by decreasing the amount of fluid transferred from blood to urine by the kidneys. This regulation of blood volume affects other aspects of the cardiovascular system. Increased or decreased blood volume influences blood pressure, which is regulated by baroreceptors, and can in turn affect the strength of ventricular contraction in the heart. Additional research has demonstrated that the subfornical organ may be an important intermediary through which leptin acts to maintain blood pressure within normal physiological limits via descending autonomic pathways associated with cardiovascular control. [1]

SFO neurons have also been experimentally shown to send efferent projections to regions involved in cardiovascular regulation including the lateral hypothalamus, 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. [5]

Relationship with other circumventricular organs

Other circumventricular organs participating in systemic regulatory processes are the area postrema and the OVLT. [1] [5] [7] 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. [5] The AV3V region is important in the regulation of fluid and electrolyte balance, by controlling thirst, sodium excretion, blood volume regulation, and vasopressin secretion. [1] [5] 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. [1] [5] [8]

Hormones and receptors

Neurons in the subfornical organ have receptors for many hormones that circulate in the blood but which do not cross the blood–brain barrier, [1] including angiotensin, atrial natriuretic peptide, endothelin and relaxin. 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 osmoreceptors, being sensitive to the osmotic pressure of the blood. These neurons project to the supraoptic nucleus and paraventricular nucleus to regulate the activity of vasopressin-secreting neurons. These neurons also project to the nucleus medianus which is involved in controlling thirst. Thus, the subfornical organ is involved in fluid balance.[ citation needed ]

Other important hormones have been shown to excite the SFO, specifically serotonin, carbamylcholine (carbachol), and atropine. These neurotransmitters however seem to have an effect on deeper areas of the SFO than angiotensin, and antagonists 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.[ citation needed ]

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, and synapse with deeper carbachol-sensitive neurons. The axons 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 circuit is suggested on the output path. [5]

Genetics

The expression of various genes in the subfornical organ have been studied. For example, it was seen that water deprivation in rats led to an upregulation of the mRNA 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 transcription factor 1 (TTF1) production, a protein generally produced in the hypothalamus. [11]

Pathology

Hypertension

Hypertension, 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. [12]

Dehydration

As stated above, angiotensin 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. [13]

Research

Feeding

Although generally viewed primarily as having roles in homeostasis and cardiovascular regulation, the subfornical organ has been thought to control feeding patterns through taking inputs from the blood (various peptides indicating satiety) and then stimulating hunger. It has been shown to induce drinking in rats as well as eating. [5]

Related Research Articles

<span class="mw-page-title-main">Hypothalamus</span> Area of the brain below the thalamus

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 hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond.

<span class="mw-page-title-main">Blood–brain barrier</span> Semipermeable capillary border that allows selective passage of blood constituents into the brain

The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside. The blood–brain barrier is formed by endothelial cells of the capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some small molecules by passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function.

<span class="mw-page-title-main">Renin–angiotensin system</span> Hormone system

The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance.

<span class="mw-page-title-main">Thirst</span> Craving for potable fluids experienced by animals

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, such as sodium. If the water volume of the body falls below a certain threshold or the osmolite concentration becomes too high, structures in the brain detect changes in blood constituents and signal thirst.

<span class="mw-page-title-main">Supraoptic nucleus</span> ADH secreting nucleus of the hypothalamus.

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 neurons.

<span class="mw-page-title-main">Paraventricular nucleus of hypothalamus</span>

The paraventricular nucleus 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 amount of vasopressin, otherwise the nucleus also secretes corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH). CRH and TRH are secreted into the hypophyseal portal system and act on different targets neurons in the anterior pituitary. PVN is thought to mediate many diverse functions through these different hormones, including osmoregulation, appetite, and the response of the body to stress.

Magnocellular neurosecretory cells are large neuroendocrine 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 circular nucleus. There are two types of magnocellular neurosecretory cells, oxytocin-producing cells and vasopressin-producing cells, but a small number can produce both hormones. These cells are neuroendocrine neurons, are electrically excitable, and generate action potentials in response to afferent stimulation. Vasopressin is produced from the vasopressin-producing cells via the AVP gene, a molecular output of circadian pathways.

The angiotensin II receptors, (ATR1) and (ATR2), are a class of G protein-coupled receptors with angiotensin II as their ligands. They are important in the renin–angiotensin system: they are responsible for the signal transduction of the vasoconstricting stimulus of the main effector hormone, angiotensin II.

<span class="mw-page-title-main">Arcuate nucleus</span>

The arcuate nucleus of the hypothalamus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. 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 astrocytes. 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 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. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.

<span class="mw-page-title-main">Median eminence</span>

The median eminence is generally defined as the portion of the ventral hypothalamus from which the portal vessels arise. The median eminence is a small swelling on the tuber cinereum, posterior to and atop the pituitary stalk; it lies in the area roughly bounded on its posterolateral region by the cerebral peduncles, and on its anterolateral region by the optic chiasm.

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 – the vascular organ of the lamina terminalis, and the subfornical organ. They contribute to osmoregulation, controlling fluid balance in the body. Osmoreceptors are also found in the kidneys where they also modulate osmolality.

Neuroendocrinology is the branch of biology which studies the interaction between the nervous system and the endocrine system; i.e. how the brain regulates the hormonal activity in the body. The nervous and endocrine systems often act together in a process called neuroendocrine integration, to regulate the physiological processes of the human body. Neuroendocrinology arose from the recognition that the brain, especially the hypothalamus, controls secretion of pituitary gland hormones, and has subsequently expanded to investigate numerous interconnections of the endocrine and nervous systems.

The vascular organ of lamina terminalis (VOLT), organum vasculosum of the lamina terminalis(OVLT), or supraoptic crest is one of the four sensory circumventricular organs of the brain, the others being the subfornical organ, the median eminence, and the area postrema in the brainstem.

<span class="mw-page-title-main">Circumventricular organs</span> Interfaces between the brain and the circulatory system

Circumventricular organs (CVOs) 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–brain barrier (BBB) at the capillary level. Although the term "circumventricular organs" was originally proposed in 1958 by Austrian anatomist Helmut O. Hofer concerning structures around the brain ventricular system, the penetration of blood-borne dyes into small specific CVO regions was discovered in the early 20th century. The permeable CVOs enabling rapid neurohumoral exchange include the subfornical organ (SFO), the area postrema (AP), the vascular organ of lamina terminalis, the median eminence, the pituitary neural lobe, and the pineal gland.

<span class="mw-page-title-main">Area postrema</span> Medullary structure in the brain that controls vomiting

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 transduce them into neural signals and networks. Its position adjacent to the bilateral nuclei of the solitary tract and role as a sensory transducer allow it to integrate blood-to-brain autonomic functions. Such roles of the area postrema include its detection of circulating hormones involved in vomiting, thirst, hunger, and blood pressure control.

<span class="mw-page-title-main">Lateral hypothalamus</span>

The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity, and eating disorders.

<span class="mw-page-title-main">Median preoptic nucleus</span> Nucleus in the anterior hypothalamus

The median preoptic nucleus is located dorsal to the other three nuclei of the preoptic area of the anterior hypothalamus. The hypothalamus is located just beneath the thalamus, the main sensory relay station of the nervous system, and is considered part of the limbic system, which also includes structures such as the hippocampus and the amygdala. The hypothalamus is highly involved in maintaining homeostasis of the body, and the median preoptic nucleus is no exception, contributing to regulation of blood composition, body temperature, and non-REM sleep.

<span class="mw-page-title-main">Tanycyte</span>

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 from the cerebrospinal fluid to the central nervous system.

Parvocellular neurosecretory cells are small neurons that produce hypothalamic releasing and inhibiting hormones. The cell bodies of these neurons are located in various nuclei of the hypothalamus or in closely related areas of the basal brain, mainly in the medial zone of the hypothalamus. All or most of the axons of the parvocellular neurosecretory cells project to the median eminence, at the base of the brain, where their nerve terminals release the hypothalamic hormones. These hormones are then immediately absorbed into the blood vessels of the hypothalamo-pituitary portal system, which carry them to the anterior pituitary gland, where they regulate the secretion of hormones into the systemic circulation.

<span class="mw-page-title-main">Septum verum</span> Region of the brain

Septum Verum is a region in the lower medial part of the telencephalon that separates the two cerebral hemispheres. The human septum consists of two parts: the septum pellucidum, a thin membrane consisting of white matter and glial cells that separate the lateral ventricles, and the lower, precommisural septum verum, which consists of nuclei and grey matter. The term is sometimes used synonymously with Area Septalis, to refer to the precommisural part of the lower base of the telencephalon. The Septum verum contains the septal nuclei, which are usually considered part of the limbic system. 

References

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  2. 1 2 Oldfield BJ, Mckinley MJ (1995). Paxinos G (ed.). The Rat Nervous System. San Diego: Academic Press. pp. 391–403. ISBN   978-0-12-547635-5.
  3. 1 2 Sposito NM, Gross PM (1987). "Topography and morphometry of capillaries in the rat subfornical organ". J Comp Neurol. 260 (1): 36–46. doi:10.1002/cne.902600104. PMID   3597833. S2CID   26102264.
  4. 1 2 Miyata, S (2015). "New aspects in fenestrated capillary and tissue dynamics in the sensory circumventricular organs of adult brains". Frontiers in Neuroscience. 9: 390. doi: 10.3389/fnins.2015.00390 . PMC   4621430 . PMID   26578857.
  5. 1 2 3 4 5 6 7 8 9 10 11 McKinley, Michael J.; Denton, Derek A.; Ryan, Philip J.; Yao, Song T.; Stefanidis, Aneta; Oldfield, Brian J. (14 March 2019). "From sensory circumventricular organs to cerebral cortex: Neural pathways controlling thirst and hunger". Journal of Neuroendocrinology. 31 (3): e12689. doi:10.1111/jne.12689. hdl: 11343/285537 . ISSN   0953-8194. PMID   30672620. S2CID   58947441.
  6. ↑ Shaver SW, Sposito NM, Gross PM (1990). "Quantitative fine structure of capillaries in subregions of the rat subfornical organ". J Comp Neurol. 294 (1): 145–52. doi:10.1002/cne.902940111. PMID   2324330. S2CID   38665940.
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  8. 1 2 3 Gross PM (1991). "Morphology and physiology of capillary systems in subregions of the subfornical organ and area postrema". Can J Physiol Pharmacol. 69 (7): 1010–25. doi:10.1139/y91-152. PMID   1954559.
  9. 1 2 3 Kawano, H.; Masuko, S. (2010). "Region-specific projections from the subfornical organ to the paraventricular hypothalamic nucleus in the rat". Neuroscience. 169 (3): 1227–34. doi:10.1016/j.neuroscience.2010.05.065. PMID   20678996. S2CID   29552630.
  10. ↑ Gross PM, Wainman DS, Chew BH, Espinosa FJ, Weaver DF (1993). "Calcium-mediated metabolic stimulation of neuroendocrine structures by intraventricular endothelin-1 in conscious rats". Brain Res. 606 (1): 135–42. doi:10.1016/0006-8993(93)91581-c. PMID   8461995. S2CID   12713010.
  11. ↑ Son YJ, Hur MK, Ryu BJ, Park SK (2003). "TTF-1, a homeodomain-containing transcription factor, participates in the control of body fluid homeostasis by regulating angiotensinogen gene transcription in the rat subfornical organ". The Journal of Biological Chemistry. 278 (29): 27043–52. doi: 10.1074/jbc.M303157200 . PMID   12730191.
  12. ↑ Bruner CA, Mangiopane ML, Fink GD (1985). "Subfornical organ. Does it protect against angiotensin II-induced hypertension in the rat?". Circ. Res. 56 (3): 462–6. doi: 10.1161/01.res.56.3.462 . PMID   3971518.
  13. ↑ Sanvitto GL, Jöhren O, Häuser W, Saavedra JM (July 1997). "Water deprivation upregulates ANG II AT1 binding and mRNA in rat subfornical organ and anterior pituitary". Am. J. Physiol. 273 (1 Pt 1): E156–63. doi:10.1152/ajpendo.1997.273.1.E156. PMID   9252492.


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