Aldosterone‐sensitive HSD2 neurons and salt appetite

Abstract

A group of aldosterone-sensitive neurons in the nucleus of the solitary tract (NTS) may play a key role in driving salt appetite. In the rat, these neurons express the mineralocorticoid receptor (MR) and the enzyme 11-β-hydroxysteroid dehydrogenase type 2 (HSD2), which makes cells sensitive to physiological concentrations of aldosterone by inactivating other corticosteroids that normally saturate MR binding sites. First, we tested the aldosterone-sensitivity and -selectivity of the HSD2 neurons. Aldosterone infusion resulted in MR nuclear translocation within the HSD2 neurons, significantly more than infusions of 100-fold higher levels of corticosterone, the rat glucocorticoid. Next, we tested whether these neurons were activated by various stimuli for salt appetite. As measured by c-Fos expression, the HSD2 neurons were signficantly activated after treatment with high-dose deoxycorticosterone, as well as dietary sodium deprivation, diuresis, and adrenalectomy. Their activation after adrenalectomy, combined with their location in the brain’s visceral input nucleus (the NTS), suggests that aldosterone is not the only input signal that drives their activation in response to sodium deficiency. Finally, the central input and output connections of the HSD2 neurons, identified using anterograde and retrograde neural tracing techniques, suggest a role in regulating salt intake. The HSD2 neurons are directly connected to sites previously implicated in sodium appetite, including the central nucleus of the amygdala, bed nucleus of the stria terminalis, and parabrachial nucleus. These aldosterone-sensitive neurons may represent a previously unrecognized central convergence point where hormonal and neural signals are integrated to drive sodium appetite.