Cell-type specific examination of central amygdala dopamine receptor 2 expressing neurons as a translational target for pharmacological enhancement of extinction

Kenneth M.MCCULLOUGH,Georgette GAFFORD,Filomene GMORRISON,,Kerry J RESSLER,

(1.Division of Depression&Anxiety Disorders,McLean Hospital,Department of Psychiatry,Harvard Medical School,Boston MA;2.Behavioral Neuroscience,Department of Psychiatry and Behavioral Sciences,Emory University,Atlanta,GA)

T1-4

Cell-type specific examination of central amygdala dopamine receptor 2 expressing neurons as a translational target for pharmacological enhancement of extinction

Kenneth M.MCCULLOUGH1,Georgette GAFFORD2,Filomene GMORRISON1,2,Kerry J RESSLER1,2

(1.Division of Depression&Anxiety Disorders,McLean Hospital,Department of Psychiatry,Harvard Medical School,Boston MA;2.Behavioral Neuroscience,Department of Psychiatry and Behavioral Sciences,Emory University,Atlanta,GA)

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 ofDrd2neurons identifies mRNAs that are differentially regulated following fear learning includingNpy5r,Rxrg,Sst5r,Fgf3,ErbB4,Fkbp14,Dlk1,Ssh3andAdora2a.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.

cell-type specific populations； fear-related disorders； central amygdala dopamine receptor 2