Impaired extinction of learned contextual fear memory in early growth response 1 knockout mice

Mol Cells. 2014 Jan;37(1):24-30. doi: 10.14348/molcells.2014.2206. Epub 2014 Jan 27.

Abstract

Inductive expression of early growth response 1 (Egr-1) in neurons is associated with many forms of neuronal activity. However, only a few Egr-1 target genes are known in the brain. The results of this study demonstrate that Egr-1 knockout (KO) mice display impaired contextual extinction learning and normal fear acquisition relative to wild-type (WT) control animals. Genome-wide microarray experiments revealed 368 differentially expressed genes in the hippocampus of Egr-1 WT exposed to different phases of a fear conditioning paradigm compared to gene expression profiles in the hippocampus of KO mice. Some of genes, such as serotonin receptor 2C (Htr2c), neuropeptide B (Npb), neuronal PAS domain protein 4 (Npas4), NPY receptor Y1 (Npy1r), fatty acid binding protein 7 (Fabp7), and neuropeptide Y (Npy) are known to regulate processing of fearful memories, and promoter analyses demonstrated that several of these genes contained Egr-1 binding sites. This study provides a useful list of potential Egr-1 target genes which may be regulated during fear memory processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Psychological
  • Early Growth Response Protein 1 / genetics*
  • Extinction, Psychological
  • Fear
  • Gene Ontology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Annotation
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Transcriptome

Substances

  • Early Growth Response Protein 1
  • Egr1 protein, mouse