Selection for contextual fear conditioning affects anxiety-like behaviors and gene expression

C. A. Ponder, C. L. Kliethermes, M. R. Drew, J. Muller, K. Das, V. B. Risbrough, J. C. Crabbe, T. Conrad Gilliam, A. A. Palmer

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Conditioned fear and anxiety-like behaviors have many similarities at the neuroanatomical and pharmacological levels, but their genetic relationship is less well defined. We used short-term selection for contextual fear conditioning (FC) to produce outbred mouse lines with robust genetic differences in FC. The high and low selected lines showed differences in fear learning that were stable across various training parameters and were not secondary to differences in sensitivity to the unconditioned stimulus (foot shock). They also showed a divergence in fear potentiated startle, indicating that differences induced by selection generalized to another measure of fear learning. However, there were no differences in performance in a Pavlovian approach conditioning task or the Morris water maze, indicating no change in general learning ability. The high fear learning line showed greater anxiety-like behavior in the open field and zero maze, confirming a genetic relationship between FC and anxiety-like behavior. Gene expression analysis of the amygdala and hippocampus identified genes that were differentially expressed between the two lines. Quantitative trait locus (QTL) analysis identified several chromosomal regions that may underlie the behavioral response to selection; cis-acting expression QTL were identified in some of these regions, possibly identifying genes that underlie these behavioral QTL. These studies support the validity of a broad genetic construct that includes both learned fear and anxiety and provides a basis for further studies aimed at gene identification.

Original languageEnglish (US)
Pages (from-to)736-749
Number of pages14
JournalGenes, Brain and Behavior
Issue number8
StatePublished - Nov 2007
Externally publishedYes


  • Anxiety
  • Behavioral genetics
  • Contextual fear conditioning
  • Correlated traits
  • Emotionality
  • Gene expression
  • Selective breeding

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience


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