Department of Molecular and Integrative Physiology and Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan.
Department of Neurology, University of Michigan, Ann Arbor, Michigan.
Genes Brain Behav. 2019 Sep;18(7):e12575. doi: 10.1111/gbb.12575. Epub 2019 May 7.
Fear conditioning is an associative learning process by which organisms learn to avoid environmental stimuli that are predictive of aversive outcomes. Fear extinction learning is a process by which avoidance of fear-conditioned stimuli is attenuated when the environmental stimuli is no longer predictive of the aversive outcome. Aberrant fear conditioning and extinction learning are key elements in the development of several anxiety disorders. The 129S1 inbred strain of mice is used as an animal model for maladaptive fear learning because this strain has been shown to generalize fear to other nonaversive stimuli and is less capable of extinguishing fear responses relative to other mouse strains, such as the C57BL/6. Here we report new environmental manipulations that enhance fear and extinction learning, including the ability to discriminate between an aversively paired tone and a neutral tone, in both the 129S1 and C57BL/6 strains of mice. Specifically, we show that discontinuous ("pipped") tone stimuli significantly enhance within-session extinction learning and the discrimination between neutral and aversively paired stimuli in both strains. Furthermore, we find that extinction training in novel contexts significantly enhances the consolidation and recall of extinction learning for both strains. Cumulatively, these results underscore how environmental changes can be leveraged to ameliorate maladaptive learning in animal models and may advance cognitive and behavioral therapeutic strategies.
恐惧条件反射是一种联想学习过程，通过该过程，生物体学会避免对预示不良后果的环境刺激做出反应。恐惧消退学习是指当环境刺激不再预示不良后果时，避免恐惧条件刺激的过程会减弱。异常的恐惧条件反射和消退学习是几种焦虑障碍发展的关键因素。129S1 近交系小鼠被用作适应性恐惧学习的动物模型，因为该品系已被证明可将恐惧泛化到其他非厌恶刺激，并且相对于其他小鼠品系（如 C57BL/6），其更难以消除恐惧反应。在这里，我们报告了新的环境操作，可增强恐惧和消退学习，包括区分令人讨厌的配对音调和中性音调的能力，在 129S1 和 C57BL/6 两种品系的小鼠中均如此。具体来说，我们表明，不连续（“发声”）的音调刺激可显著增强两种品系在单次训练中消退学习的能力，以及对中性和令人讨厌的配对刺激的区分能力。此外，我们发现，在新环境中进行消退训练可显著增强两种品系对消退学习的巩固和回忆。总之，这些结果强调了环境变化如何可以被利用来改善动物模型中的适应性学习，并可能推进认知和行为治疗策略。
