Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Interdisciplinary Neurobehavioral Core, Heidelberg University, Heidelberg, Germany.
Sci Rep. 2020 Jul 9;10(1):11263. doi: 10.1038/s41598-020-67758-0.
In humans, infancy and adolescence are associated with major changes in synaptic functions and ongoing maturation of neural networks, which underlie the major behavioral changes during these periods. Among adult cases with neuropsychiatric disorders including autism spectrum disorder, schizophrenia, attention deficit hyperactivity, and bipolar disorders, 50% have developed behavioral symptoms and received a diagnosis before 15 years of age. However, most of the behavioral studies in mice modeling neuropsychiatric phenotypes are performed in adult animals, missing valuable phenotypic information related to the effect of synaptic maturation during development. Here, we explored which behavioral experiments assessing neuropsychiatric phenotypes can be performed during a specific window of development in adolescent male and female C57BL/6N, DBA/2, and FVB/N mice that are typically used as background strains for generating genetically-modified mouse models. The three wild-type strains were evaluated across anxiety, social behaviors, and cognitive functions in order to cover the main behavioral impairments that occur in neuropsychiatric disorders. During adolescence, the three strains displayed significant differences under certain behavioral paradigms. In addition, C57BL/6N and FVB/N, but not DBA/2 mice revealed some sex-related differences. Our results provide new insights into discrete behaviors during development and emphasize the crucial importance of the genetic background, sex, and experimental settings in the age-dependent regulation of different behaviors.
在人类中，婴儿期和青春期与突触功能的重大变化以及神经网络的持续成熟有关，这些是这些时期主要行为变化的基础。在包括自闭症谱系障碍、精神分裂症、注意缺陷多动障碍和双相情感障碍在内的神经精神障碍的成年病例中，有 50%的患者在 15 岁之前出现行为症状并被诊断。然而，大多数用于模拟神经精神表型的小鼠模型的行为研究都是在成年动物中进行的，错过了与发育过程中突触成熟相关的有价值的表型信息。在这里，我们探索了在通常用作遗传修饰小鼠模型生成背景品系的 C57BL/6N、DBA/2 和 FVB/N 雄性和雌性青少年小鼠的特定发育窗口期间，可以进行哪些评估神经精神表型的行为实验。为了涵盖神经精神障碍中发生的主要行为障碍，这三种野生型品系被评估了焦虑、社交行为和认知功能。在青春期，三种品系在某些行为范式下表现出显著差异。此外，C57BL/6N 和 FVB/N 但不是 DBA/2 小鼠显示出一些与性别相关的差异。我们的研究结果为发育过程中的离散行为提供了新的见解，并强调了遗传背景、性别和实验设置在不同行为的年龄依赖性调节中的重要性。
