Fear extinction, crucial for survival, involves decreased fear responses after threat removal. Deficits in extinction can lead to PTSD. This study investigated the role of gastrin-releasing peptide (GRP) in dopamine's role in fear extinction. GRP knockout (*Grp*) mice showed enhanced fear memory in a stress-enhanced fear learning (SEFL) paradigm. In vivo fiber photometry revealed increased basolateral amygdala (BLA) dopaminergic binding in *Grp* mice during conditioning and extinction. Optogenetics and electrophysiology showed increased VTA-BLA connectivity. RNA-seq and qPCR demonstrated downregulation of dopamine-related genes in the BLA of *Grp* mice after SEFL memory recall. This research identifies GRP as a regulator of dopaminergic control of fear extinction.
Publisher
Molecular Psychiatry
Published On
Nov 23, 2024
Authors
Yoshikazu Morishita, Ileana Fuentes, Sofia Gonzalez-Salinas, John Favate, Jennifer Mejaes, Ko Zushida, Akinori Nishi, Charles Hevi, Noriko Goldsmith, Steve Buyske, Stephanie E. Sillivan, Courtney A. Miller, Eric R. Kandel, Shusaku Uchida, Premal Shah, Juan Marcos Alarcon, David J. Barker, Gleb P. Shumyatsky