Fear conditioning in C57/BL/6 and DBA/2 mice: variability in nucleus accumbens function according to the strain predisposition to show contextual‐ or cue‐based responding

Abstract

The contribution of the nucleus accumbens shell, the dorsal hippocampus, and the basolateral amygdala to contextual and explicit cue fear conditioning was assessed in C57BL/6 (C57) and DBA/2 (DBA) mice showing differences in processing contextual information associated with consistent but non-pathological variations in hippocampal functionality. Mice from both strains with bilateral ibotenic acid or sham lesions located in each area were introduced in a conditioning chamber and exposed twice to the pairing of a tone (2 x 8 s, 2000 Hz, 80 dB) with a shock (2 s, 0.7 mA). On the following day, mice were first exposed to the training context then to the tone in a different context. Freezing behaviour was scored in all situations. C57 showed more freezing to the context than to the tone whereas DBA showed more freezing to the tone than to the context. In C57, both nucleus accumbens and hippocampal lesions impaired acquisition of contextual fear conditioning but paradoxically improved acquisition of cue fear conditioning, whereas amygdala lesions disrupted performance in every task. In DBA, nucleus accumbens lesions, like amygdala lesions, impaired acquisition of both contextual and cue fear conditioning, whereas hippocampal lesions did not produce any effect. The parallelism between the effect of nucleus accumbens and hippocampus lesions in C57, and between the effect of nucleus accumbens and amygdala lesions in DBA points to a variability in nucleus accumbens function according to the strain specialization to develop context- or cue-based responding.

Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice

“…It therefore contradicts the description of the DBA/2 strain (in comparison of the C57BL/6 strain) as a model or manifestation of a loss of hippocampal function, with relatively poor performance (compared with C57BL/6 mice) in tasks requiring the formation of complex contextual representations including spatial learning as well as contextual fear conditioning (e.g. Ammassari-Teule et al 2000a, 2000bBarber et al 1974;Gerlai 1998;Paylor et al 1993Paylor et al , 1994Wehner et al 1990;Wimer et al 1976).…”

Gene and stress history interplay in emergence of PTSD-like features

“…For instance, the social stress model elicited acute social avoidance in BALB/cj in comparison to C57BL/6j (25). The single foot shock augmented social impairment in DBA/2j and behavioral "depression" in C57BL/6j (28) accompanied by diminished contextual fear conditioning (14). The predator stress model (29) found BALB/c mice more resilient than C57BL/6 and DBA/2 strains.…”

“…Such aggressive interaction is designed to make the Agg-E mice encounters as repeated life-threatening events, a critical feature of a combat theater. Typical PTSD models, such as the brief footshock model (14,26) and the predator stress model (27) fails to emulate certain key features of combat theater such as the repeated, random and uncontrolled occurrence of the potentially life-threatening events and the conspecific interactions, respectively.…”

“…Inter-strain genetic heterogeneity and the histological and endocrinological variables are often considered to be the mediator of the strain-tostrain endophenotypic variances in mice. The inter-strain variability reflected in the sizes of the hippocampus (13), nucleus accumbens (14) and neocortical elements (15), as well as the diversities in the cholinergic (16) and dopaminergic (17) feedbacks could contribute to social and cognitive plasticity (18,19).…”

“…In DBA/2j Agg-E mice, Fkbp5 remained two-fold elevated 1d and 4w post-10-exploited genetic variances among the various mouse strains to understand its contributions in shaping the social behaviors(44), accomplishing the behavioral tasks (45) and responding to various types of stress, such as brief footshock(14,28), predator's scent(29) and early life trauma(46). The dual effects of the genetic heterogeneity and the phenotypic challenges (such as changing stressor from neurological injury to emotional assault, introducing environmental novelty) on the rodents' response profile (such as fear plasticity, neurotransmission) were clearly evident.…”