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Cell-type-specific interrogation of CeA Drd2 neurons to identify targets for pharmacological modulation of fear extinction.

Translational psychiatry | 2018

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. Examining 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 novel fear-supporting neuronal population that is molecularly distinct from other, previously identified, fear-supporting CeA populations. Sequencing of actively translating transcripts of Drd2 neurons using translating ribosome affinity purification (TRAP) technology identifies mRNAs that are differentially regulated following fear learning. Differentially expressed transcripts with potentially targetable gene products include Npy5r, Rxrg, Adora2a, Sst5r, Fgf3, Erbb4, Fkbp14, Dlk1, and Ssh3. Direct pharmacological manipulation of NPY5R, RXR, and ADORA2A confirms the importance of this cell population and these cell-type-specific receptors in fear behavior. Furthermore, these findings validate the use of functionally identified specific cell populations to predict novel pharmacological targets for the modulation of emotional learning.

Pubmed ID: 30135420 RIS Download

Associated grants

  • Agency: NIH HHS, United States
    Id: U42 OD012210
  • Agency: NIMH NIH HHS, United States
    Id: T32 MH019836
  • Agency: NINDS NIH HHS, United States
    Id: T32 NS096050
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH108665
  • Agency: NIMH NIH HHS, United States
    Id: F31 MH105237

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