Genetic background differences and nonassociative effects in mouse trace fear conditioning - PubMed (original) (raw)

Comparative Study

. 2007 Sep 5;14(9):597-605.

doi: 10.1101/lm.614807. Print 2007 Sep.

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Comparative Study

Genetic background differences and nonassociative effects in mouse trace fear conditioning

Dani R Smith et al. Learn Mem. 2007.

Abstract

Fear conditioning, including variants such as delay and trace conditioning that depend on different neural systems, is widely used to behaviorally characterize genetically altered mice. We present data from three strains of mice, C57/BL6 (C57), 129/SvlmJ (129), and a hybrid strain of the two (F(1) hybrids), trained on various versions of a trace fear-conditioning protocol. The initial version was taken from the literature but included unpaired control groups to assess nonassociative effects on test performance. We observed high levels of nonassociative freezing in both contextual and cued test conditions. In particular, nonassociative freezing in unpaired control groups was equivalent to freezing shown by paired groups in the tests for trace conditioning. A number of pilot studies resulted in a new protocol that yielded strong context conditioning and low levels of nonassociative freezing in all mouse strains. During the trace-CS test in this protocol, freezing in unpaired controls remained low in all strains, and both the C57s and F(1) hybrids showed reliable associative trace fear conditioning. Trace conditioning, however, was not obtained in the 129 mice. Our findings indicate that caution is warranted in interpreting mouse fear-conditioning studies that lack control conditions to address nonassociative effects. They also reveal a final set of parameters that are important for minimizing such nonassociative effects and demonstrate strain differences across performance in mouse contextual and trace fear conditioning.

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Figures

Figure 1.

Figure 1.

Test of trace conditioning to the tone–CS under the Initial Protocol. These data were analyzed using 3 (Strain) × 2 (Training group) × 5 (Interval) factorial ANOVA (see text for the statistical results). All paired groups of mice responded with a high level of freezing to the tone–CS. However, of the unpaired groups, only the C57BL/6J mice exhibited somewhat lower levels of freezing to the tone–CS. There was no significant difference between paired and unpaired overall (no main effect of Training Group) and no interaction between Training Group and Strain. Behavior during the interval prior to presentation of the tone–CS (pre-CS period) is indicated at the 20-sec datapoint. The black bar at the 40-sec interval indicates when the tone–CS was presented; the 60-sec interval encompasses the empty trace interval until the shock occurred during training (black arrow). (●) Paired mice; (○) unpaired mice.

Figure 2.

Figure 2.

Test of contextual conditioning under the Initial Protocol. There was no overall difference between Paired (left) and Unpaired (right) groups, but the 129S1/SvImJ mice exhibited higher levels of freezing to the testing context compared with the C57BL/6J and B6129F1/J hybrid mice. Data are presented as mean ± SE.

Figure 3.

Figure 3.

Schematic representation of the 3-d trace fear-conditioning procedure for the Final Protocol. Note that the times represented by the dashed lines are not repeated.

Figure 4.

Figure 4.

Test of trace conditioning to the tone–CS under the Final Protocol. All unpaired groups of mice exhibited low nonassociative effects and low levels of freezing to the tone cue. Strain differences were evident under the Final Protocol. Only the C57BL/6J mice exhibited robust conditioning to the tone–CS, while the B6129SF1/J hybrid mice exhibited conditioning, but at a lower level. The 129S1/SvImJ mice failed to condition to the tone–CS. The 20-sec interval represents the 20 sec prior to presentation of the tone–CS (pre-CS period); the black bar (40-sec interval) indicates when the tone–CS was presented; the 60-sec interval encompasses the trace interval and the time period when the shock occurred during training (black arrow). Note that freezing levels peaked at this time point. (●) Paired mice; (○) unpaired mice.

Figure 5.

Figure 5.

Test of contextual conditioning under the Final Protocol. All three strains of mice and both Paired (left) and Unpaired (right) groups exhibited high levels of freezing to the training context and low levels to the testing context, indicating low levels of nonassociative effects.

References

    1. Balogh S.A., Wehner J.M. Inbred mouse strain differences in the establishment of long-term fear memory. Behav. Brain Res. 2003;140:97–106. - PubMed
    1. Balogh S.A., Radcliffe R.A., Logue S.F., Wehner J.M. Contextual and cued fear conditioning in C57BL/6J and DBA/2J mice: Context discrimination and the effects of retention interval. Behav. Neurosci. 2002;116:947–957. - PubMed
    1. Bangasser D.A., Waxler D.E., Santollo J., Shors T.J. Trace conditioning and the hippocampus: The importance of contiguity. J. Neurosci. 2006;26:8702–8706. - PMC - PubMed
    1. Bast T., Zhang W.N., Feldon J. Hippocampus and classical fear conditioning. Hippocampus. 2001;11:828–831. - PubMed
    1. Beauchamp G.K., Yamazaki K. Chemical signalling in mice. Biochem. Soc. Trans. 2003;31:147–151. - PubMed

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