Circulating Angiotensin II Activates Neurones in Circumventricular Organs of the Lamina Terminalis That Project to the Bed Nucleus of the Stria Terminalis

Abstract

The aim of this study was to determine, in conscious rats, whether elevated concentrations of circulating angiotensin II activate neurones in both the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) that project to the bed nucleus of the stria terminalis (BNST). The strategy employed was to colocalize retrogradely transported cholera toxin B subunit (CTB) from the BNST, with elevated levels of Fos protein in response to angiotensin II. Circulating angiotensin II concentrations were increased by either intravenous infusion of angiotensin II or subcutaneous injection of isoproterenol. Neurones exhibiting Fos in response to angiotensin II were present in the subfornical organ, predominantly in its central core but with some also seen in its peripheral aspect, the dorsal and lateral margins of the OVLT, the supraoptic nucleus and the parvo‐ and magnocellular divisions of the paraventricular nucleus. Fos‐labelling was not apparent in control rats infused with isotonic saline intravenously or injected with either CTB or CTB conjugated to gold particles (CTB‐gold) only. Of the neurones in the subfornical organ that were shown by retrograde labelling to project to BNST, approximately 50% expressed Fos in response to isoproterenol. This stimulus also increased Fos in 33% of neurones in the OVLT that project to BNST. Double‐labelled neurones were concentrated in the central core of the subfornical organ and lateral margins of the OVLT in response to increased circulating angiotensin II resulting from isoproterenol treatment. These data support a role for circulating angiotensin II acting either directly or indirectly on neurones in subfornical organ and OVLT that project to the BNST and provide further evidence of functional regionalization within the subfornical organ and the OVLT. The function of these pathways is yet to be determined; however, a role in body fluid homeostasis is possible.

Distinct neural mechanisms for the control of thirst and salt appetite in the subfornical organ

“…[Na + ] in body fluids is continuously monitored in the brain to maintain it within the physiological range (Johnson, 2007). The central monitoring of body-fluid conditions is considered to be mediated by sensory circumventricular organs (sCVOs), brain regions that lack a blood-brain barrier, but harbor neuronal cell bodies (McKinley et al, 2003). sCVOs are situated in the walls of third and fourth ventricles and accessed the body fluids through a single layer of ependymal cells.…”

“…I.1; McKinley et al, 2003). Multiple neuronal populations reside in the SFO, and some of them are known to have connections with distinct brain regions such as the OVLT, median preoptic nucleus (MnPO), paraventricular nucleus (PVN), supraoptic nucleus (SON), and so on (Johnson, 2007;McKinley et al, 2003).…”

“…Intracranial injection of Ang II stimulates the neural activity of sCVOs and induces water and salt intake (Buggy and Fisher 1974;Avrith and Fitzsimons 1980;Rowland et al, 1996;Sunn et al, 2003). Previous studies reported that some neurons in the sCVOs, where AT1a is abundantly expressed, are activated by systemic Na depletion (Fitzsimons, 1998) and that the neural activities in Na-depleted animals are supressed by intracerebroventricular injection of AT1a antagonists along with the reduction of salt-intake behaviors .…”

“…Previous studies indicated that the SFO is constituted by multiple neuronal populations projecting to multiple brain nuclei including the OVLT, ventral part of the bed nucleus of the stria terminalis (vBNST), MnPO, SON, and PVN (Mckinley et al, 2003;Johnson 2007). In the OVLT, there exist some neurons that respond to an increase of osmolality (Ciura and Bourque, 2006), suggesting a role of the OVLT in thirst responses.…”

“…The BNST is a part of the extended amygdala, which is implicated in emotional behaviors such as anxiety and reward (Stamatakis et al, 2014). Electrolytic destructions of the BNST cause reductions in salt appetite (Reilly et al, 1994), and retrogradely labeled SFO neurons from the BNST are activated by the circulating Ang II in rats (Sunn et al, 2003).…”