Visual Discrimination, Serial Reversal, and Extinction Learning in the mdx Mouse
Visual Discrimination, Serial Reversal, and Extinction Learning in the mdx Mouse
复制标题
DOI：
10.3389/fnbeh.2019.00200
复制
发表时间：
2019-08-30
影响因子：
3
通讯作者：
Mittleman, Guy
中科院分区：
文献类型：
--
作者：
Dickson, Price E.;Mittleman, Guy
Duchenne肌营养不良症(DMD)是最常见的肌营养不良症，也是最常见的神经肌肉疾病。除了神经肌肉方面的后果外，一些DMD患者还会出现全球智能障碍和机制不明的执行功能障碍。MDX小鼠是DMD最常用的小鼠模型，其认知特征尚未完全确定，也从未使用触摸屏操作条件反射范式进行过评估。触摸屏模式允许使用与人类认知测试中使用的协议几乎相同的协议，因此可能为量化小鼠的认知功能提供最具翻译性的模式。在本研究中，我们使用触摸屏范式来评估MDX突变对视觉辨别学习、序列反转学习和消亡学习的影响。为了能够测量任务依赖性的学习和记忆过程，同时保持对感觉驱动的信息处理的需求不变，我们开发了同样显著的视觉刺激，并在所有实验阶段使用它们。与野生型相比，mdx小鼠最初的成对视觉辨别能力的获得是容易的；这种影响不能用冲动、动机或运动缺陷的基因差异来解释。MDX突变对连续翻转或灭绝学习没有影响。总而言之，这项研究和以前的研究表明，MDX对认知功能的影响是特定于任务的，可能受到歧视类型(空间、视觉)、奖励类型(食物、逃离非首选环境)、性别和遗传背景的影响。
Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy and the most common neuromuscular disorder. In addition to neuromuscular consequences, some individuals with DMD experience global intellectual dysfunction and executive dysfunction of unknown mechanistic origin. The cognitive profile of the mdx mouse, the most commonly used mouse model of DMD, has been incompletely characterized and has never been assessed using the touchscreen operant conditioning paradigm. The touchscreen paradigm allows the use of protocols that are virtually identical to those used in human cognitive testing and may, therefore, provide the most translational paradigm for quantifying mouse cognitive function. In the present study, we used the touchscreen paradigm to assess the effects of the mdx mutation on visual discrimination learning, serial reversal learning, and extinction learning. To enable measuring task-dependent learning and memory processes while holding demands on sensory-driven information processing constant, we developed equally salient visual stimuli and used them on all experimental stages. Acquisition of the initial pairwise visual discrimination was facilitated in mdx mice relative to wildtype littermates; this effect was not explained by genotypic differences in impulsivity, motivation, or motor deficits. The mdx mutation had no effect on serial reversal or extinction learning. Together, findings from this study and previous studies suggest that mdx effects on cognitive function are task-specific and may be influenced by discrimination type (spatial, visual), reward type (food, escape from a non-preferred environment), sex, and genetic background.