CRFergic innervation of the paraventricular nucleus of the rat hypothalamus: a tract-tracing study.

It has been reported that corticotropin-releasing factor (CRF) may regulate its own biosynthesis in the paraventricular nucleus of the hypothalamus (PVH). Whether this CRF autoregulation is mediated by local circuitry or from extra-PVH CRF neuronal fibers terminating on CRF perikarya within the PVH is unknown. In the present study, we sought to determine the origin(s) of this CRF innervation using retrograde transport of wheat germ-conjugated-gold particles (WGA-apoHRP-Au) combined with immunohistochemistry for CRF. The rats also received colchicine (100 microg, icv) 5-7 days after tracer injection and were perfused 24 h later. Results of retrograde labeling with pressure injections of WGA-apoHRP-Au centered to PVH and subsequent immunohistochemical staining for CRF demonstrated numerous retrogradely labeled CRF neurons in the perifornical hypothalamic nucleus (PeF), the dorsolateral hypothalamic area (DA) (medial and lateral portions) and the dorsomedial nucleus of the hypothalamus (DMH). Smaller groups of CRF-ir neurons that were retrogradely labeled were found in the bed nuclei of the stria terminalis (BnST), the Barrington's nucleus (Bar) and the dorsal raphé (DR). These CRFergic pathways to the PVH may represent an anatomical substrate underlying the function of the stress-integrative PVH neurons in the autonomic, behavioral and neuroendocrine regulation during the stress response, including CRF autoregulation.