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Angiotensin (Ang) AT1 receptors are located in many regions of the brain that influence fluid and electrolyte balance. Neurons that express ATI receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT), circumventricular organs that lack a blood-brain barrier, are stimulated by systemically administered Ang II to initiate water drinking, sodium appetite and vasopressin secretion. Intracerebroventricular (ICV) injection of Ang II has a potent dipsogenic effect and also stimulates vasopressin secretion, effects probably caused mainly by an action of centrally administered Ang II on the median preoptic nucleus. Central administration of drugs that block the AT1 receptor, or prevent angiotensinogen production in the brain, inhibit drinking and vasopressin release in response to ICV injection of hypertonic saline, suggesting that angiotensin generated within the brain may have a role in body fluid homeostasis. Centrally administered Ang II also causes increased excretion of sodium by the kidney, and blockade of natriuretic responses by ICVinjection of the AT1 antagonist losartan suggests that a central angiotensinergic pathway may influence renal sodium excretion

The morphology, neural connectivity, neurochemistry and modified barrier properties of the sensory CVOs dealt with in the preceding sections are guideposts to the functions that these regions of the CNS subserve. Investigations over the past 30 years have greatly enriched our understanding of why these CVOs are built the way they are and what their physiological and pathophysiological roles may be. High on the list are sensory functions related to body fluid regulation and cardiovascular control, but clearly the sensory CVOs may also have other important roles such as that of the area postrema in vomiting and the participation of the sensory CVOs in fever. Neurosecretion into the circulation may also be a function, particularly in regard to the OVLT, where LHRH-containing neurons may release this peptide into the bloodstream (Samson et al. 1980), possibly in a cyclic manner (Wenger and Leonardelli 1980; Wenger et al. 1981; Piva et al. 1982). There is no evidence of a portal secretion from the OVLT to the anterior pituitary, and the target for this LHRH released from the OVLT is unknown (Lescure et al. 1978). In this final section we review sensory functions of the CVOs.

During the past 15 years, study of expression of genes such as c-fos and c-jun has provided invaluable tools for studying the function of either individual cells or whole populations of neurons in the CNS. This approach has been especially helpful in studying the sensory circumventricular organs, where blood-borne stimuli that do not cross the blood-brain barrier interact with neurons in these regions. After stimulation of a neuron, either through its synaptic input or hormonal receptors or by transduction of stimuli related to its sensory role, second messenger pathways are engaged. These lead to increased intracellular calcium levels that subsequently result in the increased expression of a number of genes that include c-fos. Synthesis of its encoded protein product, Fos, follows. This protein forms heterodimers with other proteins, and these bind to API sites in DNA to act as a regulator of gene transcription (Morgan and Curran 1989b). Activated neurons can thus be identified either by immunohistochemical techniques to detect Fos, the protein encoded by c-fos, or by in situ hybridisation identification of its mRNA (Morgan et al. 1987; Hunt et al. 1987; Dragunow and Faull 1989; Morgan and Curran 1989a, b; Ceccatelli et al. 1989; Hoffman et al. 1990).

The arterial supply and microvasculature of the subfornical organ have been studied in several mammalian species (human, rat, cat, rabbit). Arteries supplying the subfornical enter it both in the ventral stalk as a branch of the preoptic artery and dor-sally and caudally from branches of arteries supplying the choroid plexus (Duvernoy and Koritke 1964). In the rat, the subfornical organ receives a major supply from the subfornical artery which branches from the anterior cerebral artery. To reach the subfornical organ, the subfornical artery passes caudally over the splenium of the corpus collosum, returning rostrally under this fibre tract back towards the subfornical organ through the arachnoid tissue (Spoerri 1963). Before entering the dorsal-caudal aspect of the subfornical organ, this artery is joined by branches of the anterior and posterior choroidal arteries. Veins issuing from the choroid plexus also pass through the subfornical organ of the rat (Figure. 14b, d) and probably other species as well (Spoerri 1963; Duvernoy and Koritke 1964). Within the body of the subfornical organ, arterioles both from dorsal and ventral stalks reticulate into an extensive network of thin capillaries which are sometimes looped and reach near to the ventricular surface (Figure. 14b, c). Capillaries drain rostrally and laterally into large medial septal veins which flow dorsally and may reach the great cerebral vein of Galen.

If the subfornical organ, OVLT and area postrema function as sensors, an essential component for this function will be neural pathways linking these sensory sites to integrative and effector motor regions of the brain. Several neuroanatomical studies have mapped direct efferent connections of the sensory CVOs. These studies have utilised tracer molecules that are transported by axons from their sites of injection either in the anterograde or retrograde direction relative to neuronal cell bodies. Electrophysiological studies have also yielded data that are relevant to the neuronal connectivity of the sensory CVOs.

It is clear from several points of view that the subfornical organ is not a uniform structure. The subfornical organs of several mammalian species were described by Akert et al. (1961) and subdivided into three regions: a dorsal stalk, the body and ventral stalk. Dellmann and Simpson (1976) also recognised three divisions within the subfornical organ, and, more recently, Sposito and Gross (1987) and Shaver et al. (1990) subdivided the subfornical organ of the rat into a number of regions, largely on the basis of capillary morphology and distribution. These were rostral, transitional, central and caudal subregions, with dorsal, ventromedial and lateral zones of the latter three subregions. Other studies of neural connectivity, receptor binding, histo-chemical staining and functional neuroanatomy utilising c-fos expression are indicative of two major functional subdivisions of the rat subfornical organ: the first is a rostrodorsal ’outer shelP which includes the ventral and dorsal stalks of the original classification and dorsal and lateral zones of all regions specified by Sposito and Gross (1987); the second subdivision is a central Ventromedial core’ of the subfornical organ, corresponding to the ventromedial zone of Sposito and Gross (1987). A schematic diagram of the subdivisions of the rat subfornical organ is presented in Figure. 11.

The brain's three sensory circumventricular organs, the subfornical organ, organum vasculosum of the lamina terminalis and the area postrema lack a blood brain barrier and are the only regions in the brain in which neurons are exposed to the chemical environment of the systemic circulation. Therefore they are ideally placed to monitor the changes in osmotic, ionic and hormonal composition of the blood. This book describes their. General structure and relationship to the cerebral ventricles Regional subdivisions Vasculature and barrier properties Neurons, glia and ependymal cells Receptors, neurotransmitters, neuropeptides and enzymes Neuroanatomical connections Functions.

For the sensory CVOs to be responsive to circulating factors such as various hormones, peptides or ions, not only do they need the blood-brain barrier to be absent so that they are exposed to this environment, but specific receptors which bind these agents are necessary on the cell surface to specifically detect them.