Bed Nucleus Of The Stria Terminalis Pituitary Adenylate Cyclase Activating Peptide Projections To The Central Nervous System Regions

Pituitary adenylate cyclase activating peptide (PACAP) is a pleiotropic neuropeptide that has vast functions, ranging from behavioral, to endocrine, cardiovascular, and cellular, in which often these effects are biphasic. This paper will focus on the effects of PACAP within the central nervous system (CNS), specifically in response to stress and anxiety. PACAP has been extensively researched in terms of its effect on the stress response and is well-known for its effects in inducing anxiety-like behaviors. PACAP induces such effects through working in regions of the CNS such as the amygdala, hypothalamus, and bed nucleus of the stria terminalis (BNST). Research has shown that injecting PACAP into the BNST produces anxiogenic effects; this is backed up by in situ hybridization and mRNA studies. While it is known that BNST-PACAP signaling produces such behavior, it is not fully clear how these processes are connected to other CNS regions that are implicated in the stress-response or have been shown to hold PACAP neurons.Using Cre-recombinase technology, this study mapped BNST-PACAP projections to various CNS nuclei, specifically anterior projections to the nucleus accumbens, intrinsic BNST signaling, and posterior projections to the medial habenular nucleus (MHb), amygdala and hypothalamic regions. These projections occurred via three fiber pathways: stria terminalis, stria medullaris, and forebrain projections. The novel finding was of BNST-PACAP projections within the MHb via stria medullaris, as well as the conformation of one-directional BNST-PACAP projections to the amygdala via the stria terminalis and anterior projections to the nucleus accumbens.