Laxmi T Rao, Stork Oliver, Pape Hans-Christian
Institute of Physiology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
Behav Brain Res. 2003 Oct 17;145(1-2):89-98. doi: 10.1016/s0166-4328(03)00101-3.
Mice are favourite subjects in molecular and genetic memory research and frequently studied with classical fear conditioning paradigms that use an auditory cue (conditioned stimulus, CS(+)) to predict an aversive, unconditioned stimulus (US). Yet the conditions that control fear memory specificity and generalisation and their behavioural expression in such conditioned mice have not been analysed systematically. In the current study we addressed these issues in the most widely used mouse strain of behavioural genetics, C57Bl/6. In keeping with findings in other species we demonstrate the dependence of fear memory generalisation on training intensity (i.e. both US intensity and the number of CS(+) and US applied) after both excitatory (explicitly paired presentation of CS(+) and US) and inhibitory training (explicitly unpaired presentation of CS(+) and US). Furthermore, inhibitory overtraining was associated with changes of uncued anxiety-like behaviour in a light/dark exploration test, indicative of an emotional sensitisation reaction as consequence of a lack of US predictability. Together our results describe the qualitatively and quantitatively different increases of defensive behaviour in response to conditioned stimuli of different salience and identify training conditions that lead to fear memory generalisation and emotional sensitisation in C57Bl/6 inbred mice.
小鼠是分子和遗传记忆研究中常用的实验对象，经常使用经典恐惧条件反射范式进行研究，该范式利用听觉线索（条件刺激，CS(+)）来预测厌恶性非条件刺激（US）。然而，尚未系统分析控制恐惧记忆特异性和泛化及其在这类条件化小鼠中的行为表现的条件。在当前研究中，我们在行为遗传学中使用最广泛的小鼠品系C57Bl/6中解决了这些问题。与其他物种的研究结果一致，我们证明了在兴奋性训练（CS(+)和US明确配对呈现）和抑制性训练（CS(+)和US明确非配对呈现）后，恐惧记忆泛化对训练强度（即US强度以及CS(+)和US的呈现次数）的依赖性。此外，在明暗探索试验中，抑制性过度训练与无提示焦虑样行为的变化有关，这表明由于缺乏US可预测性而导致情绪敏感化反应。我们的研究结果共同描述了对不同显著性条件刺激的防御行为在质和量上的不同增加，并确定了导致C57Bl/6近交系小鼠恐惧记忆泛化和情绪敏感化的训练条件。
