Cell-type specific examination of central amygdala dopamine receptor 2 expressing neurons as a translational target for pharmacological enhancement of extinction / 中国药理学与毒理学杂志

ABSTRACT

Behavioral and molecular characterization of cell- type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders. Identification of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning, mirroring possible treatment strategies in humans. Here we identify the central amygdala (CeA) Drd2-expressing population as a fear-supporting population that is molecularly distinct from other, previously identified fear-supporting CeA populations. Sequencing of actively translating transcripts of Drd2 neurons identifies mRNAs that are differentially regulated following fear learning including Npy5r, Rxrg, Sst5r, Fgf3, ErbB4, Fkbp14, Dlk1,Ssh3 and Adora2a. Direct pharmacological manipulation of NPY5R, RXR, and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.