Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning

Nat Commun. 2020 Oct 14;11(1):5180. doi: 10.1038/s41467-020-18985-6.

Abstract

Fear and extinction learning are adaptive processes caused by molecular changes in specific neural circuits. Neurons expressing the corticotropin-releasing hormone gene (Crh) in central amygdala (CeA) are implicated in threat regulation, yet little is known of cell type-specific gene pathways mediating adaptive learning. We translationally profiled the transcriptome of CeA Crh-expressing cells (Crh neurons) after fear conditioning or extinction in mice using translating ribosome affinity purification (TRAP) and RNAseq. Differential gene expression and co-expression network analyses identified diverse networks activated or inhibited by fear vs extinction. Upstream regulator analysis demonstrated that extinction associates with reduced CREB expression, and viral vector-induced increased CREB expression in Crh neurons increased fear expression and inhibited extinction. These findings suggest that CREB, within CeA Crh neurons, may function as a molecular switch that regulates expression of fear and its extinction. Cell-type specific translational analyses may suggest targets useful for understanding and treating stress-related psychiatric illness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Central Amygdaloid Nucleus / cytology
  • Central Amygdaloid Nucleus / physiology*
  • Conditioning, Psychological / physiology*
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Extinction, Psychological / physiology*
  • Fear / physiology*
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Neurons / metabolism
  • RNA-Seq

Substances

  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Corticotropin-Releasing Hormone