Axon terminals containing PACAP- and VIP-immunoreactivity form synapses with CRF-immunoreactive neurons in the dorsolateral division of the bed nucleus of the stria terminalis in the rat

The bed nucleus of the stria terminalis (BST) is a highly heterogeneous forebrain structure, within which the median and lateral BST play distinct functional roles. The medial BST (BSTM) is thought to be related to sexual behavior, while the lateral BST (BSTL) may have a stress- related function. In the human brain, the BST shows marked sexual dimorphism in the distribution of vasoactive intestinal polypeptide (VIP) immunoreactive fibers and also contains a very high concentration of pituitary adenylate cyclase activating polypeptide (PACAP) immunoreactivity (ir). Using immunohistochemistry (IHC) to examine the rat brain, the present study found that both VIP and PACAP containing afferent fibers are abundant in the BSTLd (dorsolateral division of BST), but not in the BSTM. IHC did not reveal any apparent difference between the sexes in the size of distribution of either immunoreactivity. Double staining IHC showed that axonal terminals of both VIP and PACAP neurons were in close proximity to dendrites or perikarya of corticotropin releasing factor (CRF) neurons. At the electron microscopic level IHC revealed the presence of axodendritic or axosomatic synapses between VIP-ir and PACAP-ir axon terminals and CRF-ir neurons. Although the origin of PACAP-ir fibers in the BSTLd remains to be determined, these morphological findings suggest that PACAP and VIP regulate the activity of CRF neurons in the BSTLd as neurotransmitters or neuromodulators.