Stress-activated afferent inputs into the anterior parvicellular part of the paraventricular nucleus of the hypothalamus: Insights into urocortin 3 neuron activation

Urocortin 3 (Ucn 3) is a member of the corticotropin-releasing factor family, which plays a major role in coordinating stress responses. Ucn 3 neurons in the anterior parvicellular part of the paraventricular nucleus of the hypothalamus (PVHap) provide prominent input into the ventromedial nucleus of the hypothalamus (VMH), a well known satiety center, where Ucn 3 acts to suppress feeding and modulate blood glucose levels. In the present study, we first determined that Ucn 3 expression in the PVHap was stimulated by acute restraint stress. We then performed retrograde tracing with fluorogold (FG) combined with immunohistochemistry for Fos as a marker for neuronal activation after restraint stress to determine the stress-activated afferent inputs into the PVHap. Substantial numbers of FG/Fos double labeled cells were found in the bed nucleus of the stria terminalis, the lateral septal nucleus, the medial amygdala, and a number of nuclei in the hypothalamus including the VMH, the arcuate nucleus, the posterior nucleus, and the ventral premammillary nucleus. In the brainstem, FG/Fos positive cells were found in the periaqueductal gray, the nucleus of the solitary tract, and the ventrolateral medulla. In conclusion, the present study showed that acute stress rapidly stimulates Ucn 3 expression in the PVHap and identified specific stress-sensitive brain areas that project to the PVHap. These areas are potentially important in mediating the stress-induced activation of Ucn 3 neurons in the PVHap.