The subfornical organ (SFO), situated on the ventral surface of the fornix (thus the organ’s name), at the interventricular foramina (foramina of Monro), is one of the circumventricular organs of the brain, meaning that it is highly vascularized and does not have a blood-brain barrier, unlike the vast majority of regions in the brain. The SFO is a sensory circumventricular organ responsive to a wide variety of hormones and neurotransmitters, as opposed to a secretory circumventricular organ.
The central zone is composed of the glial cells, neuronal cell bodies and high density of fenestrated capillaries. Conversely, the rostral and caudal areas have lower capillary density 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 also contains endothelin receptors mediating vasoconstriction and high rates of glucose metabolism mediated by calcium channels.
General Function Of The Subfornical Organ
The subfornical organ is a circumventricular organ active in many bodily processes, including, but not limited to, osmoregulation, cardiovascular regulation, and energy homeostasis. Most of these processes involve fluid balance through the control of the release of some kind of hormone: for example angiotensin or vasopressin.
The subfornical organ’s impact on the cardiovascular system is again mostly seen through fluid balance. The SFO plays a role in vasopressin regulation.
Vasopressin is a hormone that, when bonded to receptors in the kidneys, increases water retention in the cardiovascular system by decreasing the amount of fluid transferred out of the blood to the urine by the kidneys. This regulation of blood volume has effects on other aspects of the cardiovascular system.
Increased or decreased blood volume has an effect on blood pressure, which is regulated by baroreceptors, and can in turn affect the strength of ventricular contraction in the heart, although heart rate is generally not affected by blood volume. Additional research has demonstrated that the subfornical organs 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.
SFO neurons have also been experimentally shown to broadcast 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.
Appetite And Energy Homeostasis
The subfornical organ has also been shown to have a significant impact on appetite. These mechanisms are not as clear as the neural mechanisms by which the SFO regulates fluid balance; however the most prevalent theory links the SFO’s role in appetite control to its influence on energy, particularly glucose consumption.
Recent study has focused on the SFO as an area particularly important in the regulation of energy. The observation that subfornical neurons are perceptive of a wide range of circulating energy balance signals and that electrical stimulation of the SFO in rats resulted in food intake supports the SFO’s importance in energy homeostasis.
Additionally, it is assumed that the SFO is the lone forebrain structure capable of constant monitoring of circulating concentrations of glucose, due to its lack of a blood-brain barrier. This responsiveness to glucose again serves to solidify the SFO’s integral role as a regulator of energy homeostasis.
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, 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.
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.
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.