Confirmation of contextual fear conditioning QTLs by short-term selection

A short-term selection study for contextual fear conditioning was conducted as a confirmational strategy to analyze the chromosomal locations of five previously mapped contextual fear conditioning quantitative trait loci (QTL s). The founding population was a C57BL/6 (B6) x DBA/2 (D2) F-2 intercross. High and low lines were selected for three generations based on contextual fear conditioning scores. Fear conditioning was quantified as the percenta ge of time spent in a "frozen" posture when placed back into the chamber, w here a mild footshock and a tone had been paired with exposure to the conte xt 24 h earlier. Allele frequencies of at least three SSLP DNA markers link ed to each of the five QTLs were determined in each generation. As the sele ction progressed, the frequency of D2 alleles decreased in the low line and increased in the high line for chromosomes 1 and 16, while the opposite wa s observed in chromosomes 2, 3, and 10. The direction of divergence for all eles on these five chromosomes is consistent with the original QTL mapping study. Differences between the lines in D2 allele frequencies were found to be significant for markers on chromosomes 2, 3, and 16 but did not reach s ignificance on chromosomes 1 or 10. In general, the results are in good agr eement with our original fear conditioning QTL mapping study and provide fu rther evidence that these QTLs regulate variation in contextual fear condit ioning in crosses of B6 and D2 mice.