Congenic Mouse Strains Enable Discrimination of Genetic Determinants Contributing to Fear and Fear Memory

The ability to learn and remember is variable within a population of a given species, including humans. This is due in part to genetic variation between individuals. However, only few genes have been identified that contribute to variation in learning and memory. Two inbred mouse strains, C57Bl/6J (B6) and DBA/2J (D2), show significant variation both in fear conditioning memory as well as primary responsiveness to fear. Several studies have identified quantitative trait loci (QTL) on chromosomes (Chr) 1 and 12 associated with performance in fear conditioning, but it is unclear if these QTL were associated with fear memory or innate fear responsiveness. To determine if these QTL are associated with fear memory or fear responsiveness, we studied congenic mouse strains harbouring D2-derived DNA from Chr1 or Chr12 on a B6 genetic background. Cohorts of D2, B6 and the congenic mice were tested throughout the process of fear conditioning by measuring a series of fear-related parameters. The Chr1 congenic mice showed clear deficits in fear memory compared to B6 mice, which established the presence of a QTL on Chr1 directly influencing fear memory. The Chr12 congenic mice also showed alterations in fear conditioning, but this was more associated with alterations in fear responsiveness. These findings thus provide evidence for the localisation of independent genetic determinants for fear memory and fear responsiveness.