Aldosterone‐sensitive HSD2 neurons in the nucleus of the solitary tract: gene expression and axonal projections in mice

Abstract

Dietary sodium deficiency elevates aldosterone, which in turn stimulates a unique group of neurons in the nucleus of the solitary tract (NTS). In the adult mouse brain, these NTS neurons alone express the enzyme 11‐beta‐hydroxysteroid dehydrogenase type 2 (HSD2), a hallmark of aldosterone‐sensitive cells. Here, we add detailed information about HSD2 neurons in mice, which initially were characterized in rats. First, we confirm that HSD2‐immunoreactive neurons in mice are found exclusively in the NTS. Next, using in situ hybridization, we show that these neurons robustly express Hsd11b2, the mineralocorticoid receptor (Nr3c2), vesicular glutamate transporter 2 (Slc17a6), the transcription factor Phox2b, and the angiotensin II receptor 1a (Agtr1a). Conversely, they do not express protein markers for cholinergic and monoaminergic neurons or mRNA transcripts for the peptides galanin (Gal), dynorphin (Pdyn), or angiotensinogen (Agt), which are abundant in the surrounding NTS. Next, in Hsd11b2‐Cre mice, we use Cre‐dependent axon labeling to refine conventional axon tracing data from rats. HSD2 neurons project their axons into the ipsilateral reticular formation, where they course rostrally past the trigeminal motor nucleus before turning dorsally towards the parabrachial complex (PB). There, the axons form dense terminal fields in the pre‐locus coeruleus (pLC) and an adjoining part of the medial PB subnucleus and arborize laterally in a subregion of the central lateral PB subnucleus. In addition, some axons course rostrally through the midbrain reticular formation, into the medial forebrain bundle, and ultimately form a dense terminal field in a subregion of the ventrolateral bed nucleus of the stria terminalis (BSTvL) that is homologous to the rat fusiform subnucleus. En route to the BSTvL, small numbers of axons branch and form boutons in the parasubthalamic nucleus, suprafornical lateral hypothalamic area, central nucleus of the amygdala, and paraventricular hypothalamic nucleus. Finally, using dual retrograde tracing, we found that projections to PB and BSTvL originate from separate subsets of HSD2 neurons. While their long‐range projection to BSTvL likely promotes sodium appetite, their axonal projections to PB and other sites may alter the taste of sodium and mediate other behavioral correlates of sodium depletion such as nausea, anhedonia, or fatigue.Support or Funding InformationK08 NS099425 (JCG); Aging, Mind, and Brain Institute, University of Iowa (JCG); F32 DK103387 (JMR); R01 DK075632, R01 DK096010, R01 DK089044, R01 DK111401, P30 DK046200, P30 DK057521 (BBL)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.