McCaughran J A, Bell J, Hitzemann R J
Department of Psychiatry and Neurobiology and Behavior, State University of New York at Stony Brook, 11794-8101, USA.
Pharmacol Biochem Behav. 2000 Feb;65(2):301-12. doi: 10.1016/s0091-3057(99)00216-6.
The role of genetic factors in the fear-potentiated startle (FPS) response was examined in the inbred C57BL/6J (B6) and DBA/2J (D2) mouse strains. Mice in the D2 strain displayed a significant potentiation in the acoustic startle response (ASR) when presented with a visual condition stimulus (CS) previously paired with an aversive unconditioned stimulus (US). The maximal FPS response was observed following 20 conditioning trials but a near maximal response was noted following as few as five trials. Forty conditioning trials produced a significant reduction in the FPS response that may be related to overtraining. The FPS response in the B6 strain was significantly lower than the D2 strain, regardless of the number of conditioning trials. The contrasting FPS responses were not related to differences in auditory sensitivity known to exist between these strains. Analysis of a full Mendelian cross formed from the B6 and D2 strains found that the FPS response was a highly heritable trait, best described by a simple additive model of inheritance and with a broad-sense heritability of 0.46. The distribution of the FPS response in F2 hybrids formed from the intercross of the D2 and B6 strains was continuous which suggests a multigenic substrate. The light + noise and noise-alone trial types were highly correlated, but no association was detected between the baseline ASR amplitude and the FPS response. Mice from the phenotypic extremes of the F2 distribution displayed FPS responses that were more extreme than either of the progenitor strains. However, both baseline startle amplitude and the salience of auditory stimuli did not differ in these groups. The results of this study confirm an early report by Falls et al. (1997), and provide additional quantitative genetics information necessary for the eventual mapping of the chromosomal regions or genes associated with the FPS response in mice.
在近交系C57BL/6J（B6）和DBA/2J（D2）小鼠品系中研究了遗传因素在恐惧增强惊吓（FPS）反应中的作用。当向D2品系的小鼠呈现先前与厌恶非条件刺激（US）配对的视觉条件刺激（CS）时，它们在听觉惊吓反应（ASR）中表现出显著的增强。在20次条件训练后观察到最大的FPS反应，但在仅5次训练后就注意到接近最大的反应。40次条件训练使FPS反应显著降低，这可能与过度训练有关。无论条件训练的次数如何，B6品系中的FPS反应均显著低于D2品系。这些相反的FPS反应与已知存在于这些品系之间的听觉敏感性差异无关。对由B6和D2品系形成的完整孟德尔杂交进行分析发现，FPS反应是一种高度可遗传的性状，最好用简单的加性遗传模型来描述，广义遗传力为0.46。由D2和B6品系杂交形成的F2杂种中FPS反应的分布是连续的，这表明存在多基因底物。光+噪声和仅噪声试验类型高度相关，但在基线ASR幅度和FPS反应之间未检测到关联。来自F2分布表型极端的小鼠表现出比任何一个亲本品系都更极端的FPS反应。然而，这些组中的基线惊吓幅度和听觉刺激的显著性并无差异。本研究结果证实了Falls等人（1997年）的早期报告，并提供了最终定位与小鼠FPS反应相关的染色体区域或基因所需的额外数量遗传学信息。
