Quantitative trait locus analysis of contextual fear conditioning in mice

Family, twin and adoption studies provide evidence for a substantial genetic component underlying individual differences in general intelligence1, specific cognitive abilities2 and susceptibility to psychopathologies related to fear-inducing events3. Contextual fear conditioning, which is highly conserved across species, can serve as a model for elucidating genes that regulate individual differences in learning and emotion4–. In fear conditioning, an initially neutral stimulus, such as a tone or a particular environment (context), elicits a fear response after it has been paired with an aversive stimulus, such as shock. Two neural circuits have been implicated in fear conditioning. The fear component is regulated by amygdaloid pathways, while the contextual component is, at least in part, dependent on the hippocampus9–14. C57BL/6J (B6) and DBA/2J (D2) mice differ in several types of complex learning15,16, including contextual fear conditioning17. A quantitative trait locus (QTL) analysis of contextual fear conditioning was performed in a B6/D2 F2 intercross population. Two QTLs for contextual conditioning (lod score>4.3) were identified on chromosomes 10 and 16. QTLs for conditioning to the auditory cue (lod score>4.3) were localized to chromosomes 1 and 10. Suggestive QTLs (lod score=2.8–4.1) for contextual conditioning were detected on chromosomes 1,2 and 3.