Dopamine and cyclic AMP-regulated phosphoprotein immunoreactive neurons are innervated by axon terminals immunopositive for vasoactive intestinal polypeptide in the bed nuclei of the stria terminalis and central nucleus of the amygdala

The bed nuclei of the stria terminalis (BST) and the central nucleus of the amygdala (CeA) are highly heterogeneous structures, which play a central role in the modulation and/or regulation of stress responses. The oval nucleus of the anterior division of BST (BSTov) and the CeA exhibit several dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32) immunoreactive (ir) neurons. It has been demonstrated that DARPP-32, if phosphorylated, can inhibit protein-phophatase-1, thereby controlling other neuropeptide/neurotransmitter actions. In addition, a dense network of vasoactive polypeptide (VIP) immunoreactive axon terminals was also observed here. VIP, via its receptors, increases intracellular cAMP levels, therefore it can play an important role in regulating the phosphorylation of DARPP-32. Since the localization of DARPP-32- and VIP-ir neuronal structures overlaps in the BSTov and CeA, the aim of this study was to investigate the possible synaptic innervation of DARPP-32-ir neurons by fiber terminals immunopositive for VIP, to provide anatomical evidence for the interaction between a neuropeptide and a phosphoprotein. In summary, this study for the first time demonstrated that VIP-ir axon terminals innervate DARPP-32 perikarya and dendrites in the BSTov and CeA, which play an important role in the central autonomic regulation of stress responses. In addition, morphological evidence for possible interaction between neuropeptides and phosphoproteins was also provided at the electron microscopic level.