Dickson Price E, Mittleman Guy
The Jackson Laboratory, Bar Harbor, ME, United States.
Department of Psychological Science, Ball State University, Muncie, IN, United States.
Front Behav Neurosci. 2019 Aug 30;13:200. doi: 10.3389/fnbeh.2019.00200. eCollection 2019.
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 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 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 mice relative to wildtype littermates; this effect was not explained by genotypic differences in impulsivity, motivation, or motor deficits. The mutation had no effect on serial reversal or extinction learning. Together, findings from this study and previous studies suggest that 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.
杜兴氏肌肉营养不良症(DMD)是最常见的肌肉营养不良形式,也是最常见的神经肌肉疾病。除了神经肌肉方面的后果外,一些患有DMD的个体还经历了机制不明的整体智力功能障碍和执行功能障碍。小鼠是最常用的DMD小鼠模型,其认知特征尚未完全明确,且从未使用触摸屏操作性条件反射范式进行评估。触摸屏范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认知功能提供最具转化性的范式。在本研究中,我们使用触摸屏范式评估了该突变对视觉辨别学习、连续反转学习和消退学习的影响。为了在保持对感官驱动信息处理的要求不变的同时测量与任务相关的学习和记忆过程,我们开发了同样突出的视觉刺激,并在所有实验阶段使用它们。与野生型同窝小鼠相比,突变小鼠在最初的成对视觉辨别学习中更容易习得;这种效应不能用冲动性、动机或运动缺陷的基因型差异来解释。该突变对连续反转学习或消退学习没有影响。总之,本研究和先前研究的结果表明,该突变对认知功能的影响是特定于任务的,可能受到辨别类型(空间、视觉)、奖励类型(食物、逃离非偏好环境)、性别和遗传背景的影响。