Direct projection from the suprachiasmatic nucleus to hypophysiotrophic corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus of the hypothalamus demonstrated by means of Phaseolus vulgaris-leucoagglutinin tract tracing

The diurnal rhythm of the activity of the hypothalamo-pituitary-adrenal axis is generated by the circadian pacemaker located in the suprachiasmatic nuclei (SCN). However, the neuronal circuit connecting the SCN with the neurosecretory corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus is not clear. To investigate the existence of a direct link between the SCN and the CRF neurons in the PVN we combined microiontopheretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the SCN with immunohistochemical detection of CRF in adrenalectomized male rats. The majority of the PHA-L-ir axons originating from the SCN terminated in the subparaventricular area. A minor contingent of fibers continued into the PVN proper, involving the medial and dorsal parvicellular subnuclei of the PVN. All PHA-L injections involving the entire SCN gave rise to PHA-L positive fibers endowed with boutons en passage and terminal boutons contacting CRF positive cell bodies in the PVN. Notably, varicosities on the PHA-L labelled fibers were present in close proximity to cell bodies and proximal dendrites of a subportion of the CRF neurons located in the periphery of the CRF cell cluster. The present study provides the first evidence to suggest a direct connection between the SCN and the CRF producing neurons of the hypothalamo-pituitary-adrenocortical axis in the PVN. Considering the sparse number of PHA-L-ir varicosities in close proximity to the CRF-ir cells, it seems likely that this direct pathway constitutes but a part of a projection system from the SCN, possibly involving multisynaptic pathways, influencing the hypothalamo-pituitary-adrenocortical axis.