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

Abstract

Summary The 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 provide a new understanding of the role of the Tac2 gene and CeM in fear processing and may provide novel approaches to intervention for fear-related disorders.

Susceptibility and Resilience to Posttraumatic Stress Disorder–like Behaviors in Inbred Mice

“…Specificity of the BLA subdissection was first established by ensuring low expression of the central amygdala (CeA)-specific marker, Tac2 (61), compared to adjacent CeA punches (Supplemental Figure S8). RNA-Seq identified 61 differentially expressed genes (DEG) between SS and SR (Figure 5D).…”

Elucidating an Affective Pain Circuit that Creates a Threat Memory

“…Our results also reveal that the CGRPR neuronal population partially overlaps with PKC-δ (CeAl off ) neurons in caudal CeAl, but much less so in rostral CeAl (Figure 5D–F). PKC-δ neurons also partially overlap with tachykinin 2 (Tac2; ~50%) (Cai et al, 2014) and oxytocin receptor (Oxtr; ~65%) (Haubensak et al, 2010) neuronal populations, both of which are known to suppress fear expression (Andero et al, 2014; Knobloch et al, 2012). These results suggest that PKC-δ is expressed in the multiple populations of neurons in the CeAl; the CeAl off neurons may represent the subpopulation of PKC-δ neurons that is Tac2 + , and/or Oxtr + , but CGRPR13 negative.…”

Pituitary Adenylate Cyclase Activating Polypeptide in Stress-Related Disorders: Data Convergence from Animal and Human Studies

“…Ressler and colleagues reported that mRNA for the PAC1 receptor ( ADCYAP1R1 ) increased 1.5 fold during the consolidation of fear following a standard fear conditioning protocol, and significantly correlated with fear expression (freezing behavior), and this effect can be attenuated with a NK3R antagonist (78). However, data from PAC1 receptor-null mice were less conclusive.…”