PACAP neurons of the ventral dentate gyrus are not involved in fear acquisition.

The neural mechanisms underlying learned affective responses remain a core question in affective neuroscience. The ventral dentate gyrus (vDG) has been implicated in variants of fear conditioning (i.e., contextual and cued) and may rely on pituitary adenylate cyclase-activating polypeptide (PACAP) pathways, given their role in regulating stress responses and the formation of fear memories. The current study investigated whether PACAP neurons in the vDG are also involved in fear learning by chemogenetically exciting or inhibiting them in PACAP-Cre mice during fear acquisition. We first confirmed that clozapine-N-oxide (CNO), our DREADD ligand, did not have any undesired off-target (i.e., DREADD-independent) effects on fear acquisition. The results of our subsequent experiments clearly showed that, at the mild shock intensity, fear learning in male PACAP-Cre mice does not depend on local modulation of PACAP-expressing neuronal activity in the vDG. These findings suggest that modulation of PACAP-expressing neuronal activity in the vDG does not appear to be critical for fear conditioning under certain circumstances.