BRAIN RESEARCH ELSEVIER Brain Research 713 (1996) 17-28 Research report Effect of lesions of forebrain circumventricular organs on c-fos expression in the central nervous system to plasma hypernatremia Susan L. Hochstenbach, John Ciriello * Department of Physiology, Health Science Centre, University of Western Ontario, London, N6A 5C1 Ont., Canada Accepted 31 October 1995 Abstract Experiments were carried out on conscious adult male Wistar rats to investigate the effect of selective ablation of the subfornical organ (SFO), and/or the anteroventral third ventricular (AV3V) region on the induction of Fos in central structures in response to plasma hypernatremia. Fos induction, detected immunohistochemically, was used as a marker for neuronal activation. Intravenous infusions of hypertonic saline resulted in dense Fos-like immunoreactivity in several forebrain (paraventricular nucleus of the hypothalamus (PVH), supraoptic nucleus (SON), median preoptic nucleus (MnPO), medial preoptic nucleus, organum vasculosum of the laminae terminalis and SFO) and brainstem (nucleus of the solitary tract, ventrolateral medulla, and parabrachial nucleus) structures. Intravenous infusions of the hypertonic saline solution into animals with lesions of either the SFO, the AV3V or both resulted in a decreased number of Fos-like immunoreactive neurons in the MnPO, PVH and SON. In addition, the number of Fos-labeled neurons in the SON after lesions of both the SFO and the AV3V was significantly greater than that observed in isotonic saline infused controls. Finally, lesions of the forebrain circumventricular structures did not alter the Fos labeling in brainstem structures as a result of the infusion of the hypertonic solution. These data suggest that changes in plasma osmolality and/or concentration of sodium alter the activity of SON and brainstem neurons in the absence of afferent inputs from the SFO and AV3V. Keywords: Paraventricular nucleus of the hypothalamus; Supraoptic nucleus; Nucleus of the solitary tract; Cardiovascular regulation; Subfornical organ; Anteroventral third ventricle; Organum vasculosum of the laminae terminalis 1. Introduction Traditionally, it has been accepted that central struc- tures that participate in body fluid homeostatic mecha- nisms are localized to areas that line the laminae of the third ventricle [4,6,8,9,42] and/or have an incomplete blood-brain barrier [44,85]. In particular, activation of neurons in the subfornical organ (SFO) and the organum vasculosum of the laminae terminalis (OVLT), in the anteroventral third ventricle (AV3V) region, by plasma hypernatremia and circulating angiotensin II have been shown to evoke natriuresis, thirst, arterial hypertension and the release of arginine vasopressin [5,7,10,30,43,55,79,80]. These physiological effects are thought to be mediated by projections from the SFO and the region of the AV3V to other areas of the forebrain and brainstem known to be involved in body fluid and cardiovascular regulation [11,14,15,31,40,41,45,60,75,88]. In addition, lesions * Corresponding author. Fax: (1) (519) 661-3827. 0006-8993/96/$15.00 © 1t}96 Elsevier Science B.V. All rights reserved SSDI 0006-8993(95)01425-X [12,13] or blocking neuronal activity following the applica- tion of anesthetic in the AV3V region [14,40] have been shown to reduce the responsiveness of paraventricular nucleus of hypothalamus (PVH) and supraoptic nucleus (SON) magnocellular neurosecretory neurons to dehydra- tion. Furthermore, removal of the efferent output of the SFO as a result of the application of local anesthetics to the SFO, has been shown to reduce the excitatory effects of intracarotid infusions of hypertonic saline solutions on PVH magnocellular neurons [83]. It is interesting to note that PVH parvocellular neurons that receive SFO inputs [69] have been shown to influence autonomic output via their projections to brainstem cardiovascular structures: the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), nucleus ambiguus (AMB) and the intermediolat- eral cell column of the spinal cord [54,74,82]. Taken together, these data suggest that the SFO and structures within the AV3V region, such as the OVLT, are important in the transduction of osmotic signals that lead to auto- nomic, behavioral and hormonal regulation of body fluid balance and arterial pressure.