Genetic relationship between anxiety-related and fear-related behaviors in BXD recombinant inbred mice

Mood and anxiety disorders, and rodent phenotypic measures modeling these disorders, have a strong genetic component. Various assays are used to study the neurobiological basis of fear-related and anxiety-related behaviors, phenotype genetically modified mice, and elucidate pharmacological modulation of these behaviors for medication development. Earlier work, however, suggests that different trait measures are mediated by partly overlapping but ultimately distinct genetic factors. In this study, we assessed a novel panel of 23 C57BL/6JxDBA/2J (BXD) recombinant inbred strains on various trait measures of Pavlovian fear conditioning and anxiety-like behavior (novel open field, elevated plus-maze), as well as sensory (acoustic startle, prepulse inhibition of startle) and motor (baseline coordination and learning on accelerating rotarod) function. Results showed that traits were continuously distributed across strains and had modest to strong R values. Principal components analysis resolved the data into five factors: factor 1 loaded fear-related traits, factor 2 loaded elevated plus-maze measures as well as context fear, factor 3 loaded novel open field measures and plus-maze closed arm entries, factor 4 loaded rotarod motor function, and factor 5 loaded acoustic startle and prepulse inhibition. These data add to evidence that murine measures of fear-like and anxiety-like traits reflect distinct constructs mediated by dissociable gene variants.