Subfornical organ

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]

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]

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]

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.

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.[5]

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]