Neural signalling of salt intake. The neural integration of mammalian salt-sensing mechanisms has been a source of considerable controversy. The studies proposed here will, for the first time, reveal the central neural circuitry involved in mediating splanchnic salt-sensation. A new splanchnic osmosensory area is studied in awake, unrestrained rats with indwelling gastric and arterial catheters. Multiple assays of plasma vasopressin serve as an index of receptor stimulation following gastric and systemic saline infusions. Systemic plasma osmolality, arterial blood pressure and heart rate are also measured as a control. The hypothesis is tested that splanchnic osmotic signals travel from the thoracic cord to the ventrolateral medulla, and ascend via the catecholaminergic bundles to the median preoptic nucleus, and from there to magnocellular vasopressinergic neurons. Known alternative pathways and cell groups are also tested. Objective 1 is to determine the neural substrate required for splanchnic osmosensation in rats bearing specific electrolytic lesions of the pontine catecholaminergic bundles, sublocus coeruleus, locus coeruleus, caudal periaqueductal gray, lateral parabrachial nuclei, medial dorsal pons, nucleus tractus solitarius, or median preoptic nucleus. Objective 2 is to determine the role of catecholaminergic pathways in rats bearing 6-OH-dopamine lesions of crucial CNS areas uncovered in the above experiments. Objective 3 is to determine the brain nuclei involved in splanchnic osmosensation by microinjections of ibotenic acid into the crucial cell groups. This neurotoxin impairs cell bodies but not axons in passage. Control experiments will include sham lesions; microinjections of 5,7-dihydroxytryptamine to mimick the non-specific effects of 6-OH-dopamine; microinjections of vehicle; and intra-ventricular injections of neurotoxins to control for leakage into CSF. The lesions are verified by histological reconstruction of the lesion site, and the consequences of the lesions on catecholaminergic neurons are determined by immunocytochemistry for dopamine Beta-hydroxylase. The rate of gastrointestinal absorption of radioactive NaCl is measured separately to indicate whether the lesions affect the osmotic stimulus profile at postabsorptive receptor sites. The experimental model developed over the past 3 years provides an unique opportunity for resolving important questions regarding the neural integration of the splanchnic salt-detectors.
| Baertschi, A J (1994) Antisense oligonucleotide strategies in physiology. Mol Cell Endocrinol 101:R15-24 |
| King, M S; Baertschi, A J (1992) Ventral pontine catecholaminergic pathway mediates the vasopressin response to splanchnic osmostimulation in conscious rats. Brain Res 580:81-91 |
| Baertschi, A J; Audigier, Y; Lledo, P M et al. (1992) Dialysis of lactotropes with antisense oligonucleotides assigns guanine nucleotide binding protein subtypes to their channel effectors. Mol Endocrinol 6:2257-65 |
| King, M S; Baertschi, A J (1991) Central neural pathway mediating splanchnic osmosensation. Brain Res 550:268-78 |
