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

Full Abstract

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.

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Author information

Author/s: Ponder, C A (CA); Kliethermes, C L (CL); Drew, M R (MR); Muller, J (J); Das, K (K); Risbrough, V B (VB); Crabbe, J C (JC); Gilliam, T Conrad (TC); Palmer, A A (AA);

Affiliation: Department of Genetics and Development, Columbia University, New York, NY, USA.

Grants: AA10270 (Agency:NIAAA NIH HHS) ; AA12714 (Agency:NIAAA NIH HHS) ; MH70933 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Genes, brain, and behavior (Genes Brain Behav), published in England. (Language: eng)

Reference: 2007-Nov; vol 6 (issue 8) : pp 736-49

Dates: Created 2007/11/05; Completed 2008/01/29;

PMID: 17309658, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amygdala - metabolism
Animals
Anxiety - genetics; metabolism; psychology
Association Learning - physiology
Conditioning, Classical - physiology
Environment
Fear - physiology; psychology
Female
Freezing Reaction, Cataleptic - physiology
Gene Expression Regulation
Gene Frequency

Gene Frequency
Hippocampus - metabolism
Male
Maze Learning - physiology
Mice
Mice, Inbred Strains
Oligonucleotide Array Sequence Analysis
Quantitative Trait Loci - genetics; physiology
Selection (Genetics)
Species Specificity
Startle Reaction - genetics; physiology

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