Bove Maria, Ike Kevin, Eldering Adriaan, Buwalda Bauke, de Boer Sietse F, Morgese Maria Grazia, Schiavone Stefania, Cuomo Vincenzo, Trabace Luigia, Kas Martien J H
Groningen Institute for Evolutionary Life Science, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands; Department of Physiology and Pharmacology "V. Erspamer", "Sapienza" University of Rome, Piazzale Aldo Moro, 5, 00185, Rome, Italy.
Groningen Institute for Evolutionary Life Science, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
Behav Brain Res. 2018 May 15;344:9-19. doi: 10.1016/j.bbr.2018.02.003. Epub 2018 Feb 7.
Disrupted sociability and consequent social withdrawal are (early) symptoms of a wide variety of neuropsychiatric diseases, such as schizophrenia, autism spectrum disorders, depressive disorders and Alzheimer's disease. The paucity of objective measures to translationally assess social withdrawal characteristics has been an important limitation to study this behavioral phenotype, both in human and rodents. The aim of the present study was to investigate sociability and social withdrawal in rodents using an ethologically valid behavioral paradigm, the Visible Burrow System (VBS). The VBS mimics a natural environment, with male and female rodents housed together in an enclosure where a large open arena is connected to a continuously dark burrow system that includes 4 nest boxes. In this study, mixed-sex colonies of C57BL/6J and of BTBR mice have been investigated (n = 8 mice per colony). Results showed marked differences between the two strains, in terms of sociability as well as social withdrawal behaviors. In particular, BTBR mice performed less social behaviors and have a preference for non-social behaviors compared to C57BL/6J mice. Neurobiologically, the decreased sociability of BTBR was accompanied by reduced GABA and increased glutamate concentrations in brain prefrontal cortex (PFC) and amygdala regions. In conclusion, our study validated the use of the VBS as an ethologically relevant behavioral paradigm in group-housed mice to investigate individual sociability and social withdrawal features and their underlying neurobiology. This paradigm may provide new insights to develop new therapeutic treatments for behavioral dysfunctions that may be relevant across neuropsychiatric diseases.
社交能力受损及随之而来的社交退缩是多种神经精神疾病（如精神分裂症、自闭症谱系障碍、抑郁症和阿尔茨海默病）的（早期）症状。在人类和啮齿动物中，用于转化评估社交退缩特征的客观测量方法匮乏，这一直是研究这种行为表型的一个重要限制。本研究的目的是使用一种符合行为学原理的行为范式——可视洞穴系统（VBS）来研究啮齿动物的社交能力和社交退缩情况。VBS模拟自然环境，将雄性和雌性啮齿动物饲养在一个围栏中，其中一个大的开放场地与一个连续黑暗的洞穴系统相连，该系统包括4个巢箱。在本研究中，对C57BL/6J和BTBR小鼠的混合性别群体进行了研究（每个群体n = 8只小鼠）。结果显示，在社交能力和社交退缩行为方面，这两个品系之间存在显著差异。特别是，与C57BL/6J小鼠相比，BTBR小鼠表现出较少的社交行为，并且偏好非社交行为。从神经生物学角度来看，BTBR小鼠社交能力的下降伴随着大脑前额叶皮质（PFC）和杏仁核区域γ-氨基丁酸（GABA）浓度降低和谷氨酸浓度升高。总之，我们的研究验证了VBS作为一种符合行为学原理的行为范式，可用于群居小鼠中研究个体的社交能力和社交退缩特征及其潜在的神经生物学机制。这种范式可能为开发针对可能与多种神经精神疾病相关的行为功能障碍的新治疗方法提供新的见解。
