Abstract We have discovered a highly specialized innervation of the forebrain by pituitary adenylate cyclase activating polypeptide (PACAP) immunohistochemistry originating from the brain stem that uses glutamate, acetylcholine and PACAP and other peptides as neurotransmitters. The parent neurons of the axons are in the Kölliker-Fuse nucleus and their terminals form calyx-like multi-release site synapses in the rodent forebrain extended amygdala similar to the calyx of Held in the auditory brain