Identification of Quantitative Trait Loci Involved in Contextual and Auditory-Cued Fear Conditioning in BXD Recombinant Inbred Strains

Fear conditioning shows associations formed between contextual or auditory stimuli with an unconditioned stimulus. Inbred mouse strains differ in their ability to demonstrate fear conditioning, suggesting at least a partial genetic influence. The present study identified the possible chromosomal loci regulating fear conditioning in BXD recombinant inbred strains using quantitative trait loci (QTL) analysis. Estimates of heritability for all 3 measures of conditioning were about .28. Correlational analyses between genetic markers and strain means identified multiple putative QTLs. The strongest associations were on Chromosomes 1 and 17 for freezing to the context, Chromosome 12 for freezing to an altered context, and Chromosome 1 for freezing to the auditory stimulus. Overlapping QTLs may indicate some common genes that underlie aspects of this learning task. When rats or mice are given a conditioning experience involving the pairing of a phasic auditory cue and shock, they will later display fear (as measured by a naturally occurring defensive freezing response; Fanselow, 1994) to both the static cues of the environment (the context) in which the shock occurred and to the auditory cue. There has been recent interest in contextual and auditory cue fear conditioning because they appear to depend on different neural processes. This hypothesis has been supported by recent studies showing that several variables that impair contextual fear conditioning have no effect on auditory-cue fear conditioning. For example, (a) damage to the hippocampal formation impairs contextual but not auditory-cue fear conditioning (Kim & Fanselow, 1992; Logue, Paylor, & Wehner, in press; Phillips & LeDoux, 1992, 1994), (b) contextual but not auditory-cue fear conditioning can be disrupted by postcondition ing isolation (Rudy, 1996), and (c) contextual fear conditioning emerges later in development than auditory-cue fear conditioning (Rudy, 1993). There is also evidence that genetic variation influences these two types of fear conditioning. Paylor, Tracy, Wehner, and Rudy (1994) reported that, following either a single- or multiple-conditioning trial, inbred DBA/2 mice display