Axon terminals containing CGRP-immunoreactivity form synapses with CRF- and Met-enkephalin-immunopositive neurons in the laterodorsal division of the bed nucleus of the stria terminalis in the rat

The lateral division of the bed nucleus of the stria terminalis (BSTL) is an important forebrain structure that relays information between limbic structures and the hypothalamus. The BSTL displays a very dense calcitonin gene-related peptide-immunoreactive (-ir) fiber terminal network, and contains a substantial number of the corticotropin releasing factor (CRF)-ir neurons. Several Met-enkephalin-ir perikarya have also been observed in the BSTL. The distributions of CRF- and Met-enkephalin-ir neurons and that of the calcitonin gene-related peptide (CGRP)-ir axon terminals overlap within the BSTL, suggesting synaptic connections between CRF- and Met-enkephalin-ir neurons and axon terminals immunoreactive for CGRP. Double staining immunohistochemistry revealed that CGRP-ir axon terminals were within close proximity to dendrites or perikarya of corticotropin releasing factor and Met-enkephalin-ir neurons. When viewed at the electron microscopic level, axodendritic or axosomatic synapses between CGRP-ir fiber terminals and neurons immunoreactive for CRF and Met-enkephalin were detected. Most of the CRF-ir neurons project to brainstem centers, which modulate the physiological changes accompanying stress, whereas the Met-enkephalin-ir perikarya are most likely interneurons that often colocalize with GABA. The parabrachial nucleus, a vital autonomic center, is the primary source of CGRP-ir fiber terminals to the BSTL. The synaptic contacts between the CGRP axon terminals and CRF- and Met-enkephalin-ir neurons underlie the importance of connections between autonomic brainstem centers and BSTL, which can be fundamental in the modulatory control of endocrine, physiological and behavioral responses during stress.