A Role for Tac2, NkB, and Nk3 Receptor in Normal and Dysregulated Fear Memory Consolidation

• Tac2 is associated with memory consolidation in naive mice and a PTSD-like model
• Antagonism of the Tac2 receptor restores normal and dysregulated fear consolidation
• Tac2 colocalizes with GAD65 and CaMKIIα but not with PKCd or Enk neurons in the CeM
• Tac2 neurons are required for the modulation of fear memory consolidation in the CeA

SummaryThe centromedial amygdala (CeM), a subdivision of the central amygdala (CeA), is believed to be the main output station of the amygdala for fear expression. We provide evidence that the Tac2 gene, expressed by neurons specifically within the CeM, is required for modulating fear memories. Tac2 is colocalized with GAD65 and CaMKIIα but not with PKCd and Enk neurons in the CeM. Moreover, the Tac2 product, NkB, and its specific receptor, Nk3R, are also involved in the consolidation of fear memories. Increased Tac2 expression, through a stress-induced PTSD-like model, or following lentiviral CeA overexpression, are sufficient to enhance fear consolidation. This effect is blocked by the Nk3R antagonist osanetant. Concordantly, silencing of Tac2-expressing neurons in CeA with DREADDs impairs fear consolidation. Together, these studies further our understanding of the role of the Tac2 gene and CeM in fear processing and may provide approaches to intervention for fear-related disorders.