User:Ronodeep.srimani/sandbox
| Ronodeep.srimani/sandbox | |
|---|---|
 Mesal 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 |
| Anatomical terms of neuroanatomy | |
The subfornical organ (SFO), situated on the ventral surface of the fornix(the reasoning behind the organ's name), at the interventricular foramina (foramina of Monro), is one of the circumventricular organs of the brain, meaning that it does not have a blood brain barrier, unlike the vast majority of regions in the brain.
Anatomy
Similar to the OVLT, the subfornical organ is a sensory CVO situated in the lamina terminalis and lacking the BBB, the absence of which characterizes the circumventricular organs. Protruding into the third ventricle of the brain, the highly vascularized SFO can be divided into three anatomical zones.[1] The central zone is comprised exclusively of the glial cells and neuronal cell bodies. Conversely, the rostral and caudal areas are mostly made of nerve fibers while very few neurons and glial cells can be seen in this area.[1] Functionally, however, the SFO may be viewed in two portions, the dorsolateral peripheral (pSFO) division and the ventromedial core segment.[2]
Study of subfornical organ anatomy is still ongoing but recent evidence has demonstrated the presence of endothelin (a potent vasoconstrictor) receptors.[1] This seems logical as SFO neurons have been shown to be intrinsically osmosensitive.[1] Finally, it has been established that SFO neurons maintain resting membrane potential in the range of -57 to -65 mV.[1]
General Function
The subfornical organ is a circumventricular organ active in many bodily processes including, but not limited to, osmoregulation,[2] cardiovascular regulation,[2] [3] and energy homeostasis.[3] In a study by Ferguson, both hyper- and hypotonic stimuli facilitated an osmotic response.[1] Most of these processes involve fluid balance through the control of the release of some kind of hormone: for example angiotensin or vasopressin.
Cardiovascular Regulation
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 effect the strength of ventricular contraction in the heart, although heart rate is generally not effected by blood volume. Additional research has demonstrated that the subfornical organs may be an important intermediary though which leptin acts to maintain blood pressure within normal physiological limits via descending autonomic pathways associated with cardiovascular control.[3]
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.[1]
Appetite
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.[4] Additionally, it is assumed that the SFO is the lone forebrain structure capable of constant monitoring of circulating concentrations of glucose.[4] This responsiveness to glucose again serves to solidify the SFO’s integral role as a regulator of energy homeostasis.[4]
Relationship With Other Circumventricular Organs
Other circumventricular organs are the area postrema in the brainstem and the organum vasculosum of the lamina terminalis (OVLT).
The OVLT and the SFO are both strongly 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 AV3V region is very important in the regulation of fluid and electrolyte balance, by controlling thirst, sodium excretion, blood volume regulation, and vasopressin secretion.
The SFO is outside the blood–brain barrier, and so neurons in this region can respond to factors that are present in the systemic circulation. The circumventricular organs express high density of Glucagon-like peptide 1 (GLP-1)receptors and participate in the central regulation of energy intake.
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 seratonin, 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].
Pathology
Hypertension
Colitis
Dehydration
Relevant Experiments
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 bloodstream (various peptides indicating satiety) and then stimulating hunger. It has been shown to induce drinking in ratsas well as eating.
One study looks at different stimulation current values, to determine if this has an effect on the amount of feeding that occurs. The rats studied were separated into three groups: rats with electrodes in their subfornical organ with no current passing through (sham), rats with stimulated subfornical organs, and rats with areas other than the subfornical organ stimulated. The group with stimulated subfornical organs was separated into groups with 100mA and 200mA stimulations. All rats were satiated (food and drink) before observations/stimulations were done, and were also monitored for general activity. The group with subfornical stimulation at 100mA drank an increased amount, but did not consume any additional food, and the group with 200mA consumed both more water and more food. All groups without subfornical organ stimulation did not eat or drink at all [6].
Other studies look specifically at drinking, as the SFO is known to have an important role in fluid balance. One such study looked into the connection between the SFO and the median preoptic nucleus. Rats with both partially or fully severed connections to the median preoptic nucleus showed a significantly decreased tendency to drink water when compared to the control group. Then when angiotensin was injected subcutaneously, drinking incidence went back to original levels. These findings are consistent with a model that postulates that osmoreceptors and angiotensin receptors in the SFO send excitatory neural information to the median preoptic nucleus for the mobilization of thirst. [7]
Cardiovascular Regulation
Genetics
Possible Treatments
Absence of Blood-Brain Barrier
References
- ^ a b c d e f g Ferguson, A. V., & Bains, J. S. (1996). Electrophysiology of the circumventricular organs. Frontiers in Neuroendocrinology, 17(4), 440-475. doi: 10.1006/frne.1996.0012.
- ^ a b c Kawano, H., and Masuko, S. (2010). Region-specific projections from the subfornical organ to the paraventricular hypothalamic nucleus in the rat. Neuroscience 169, 1227-1234.
- ^ a b c Smith, P. M. and Ferguson, A. V. (2012), Cardiovascular Actions of Leptin in the Subfornical Organ are Abolished by Diet-Induced Obesity. Journal of Neuroendocrinology, 24: 504–510. doi: 10.1111/j.1365-2826.2011.02257.x.
- ^ a b c Medeiros, N., Dai, L., and Ferguson, A.V. (2012). Glucose-responsive neurons in the subfornical organ of the rat—a novel site for direct CNS monitoring of circulating glucose. Neuroscience 201, 157-165.
- ^ Buranarugsa P, Hubbard J I (1978). "The neuronal Organization of the rat subfornical organ in vitro and a test of the osme- and morphine receptor hypotheses". J. Physiol. 291 (4): 101–16.
- ^ Smith P, (2010). "Acute electrical stimulation of the subfornical organ induces feeding in satiated rats". Physiology and Behavior. 99 (4): 534–37.
{{cite journal}}: CS1 maint: extra punctuation (link) - ^ Lind R. Wallace, (1982). "Subfornical organ-median preoptic connections and drinking and pressor responses to angiotensin II". PThe Journal of Neuroscience. 2 (3): 1043–51.
{{cite journal}}: CS1 maint: extra punctuation (link)