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自闭症相关基因 Pcdh10 缺失的小鼠存在年龄和性别特异性的恐惧条件反射缺陷。

Age- and sex-specific fear conditioning deficits in mice lacking Pcdh10, an Autism Associated Gene.

机构信息

Iowa Neuroscience Institute, Department of Neuroscience and Pharmacology, University of Iowa, 169 Newton Road, 2312 Pappajohn Biomedical Discovery Building, Iowa City, IA 52242, USA.

Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Translational Research Laboratory, 125 South 31(st) Street, Room 2202, Philadelphia, PA 19104-3403, USA.

出版信息

Neurobiol Learn Mem. 2021 Feb;178:107364. doi: 10.1016/j.nlm.2020.107364. Epub 2020 Dec 16.

Abstract

PCDH10 is a gene associated with Autism Spectrum Disorder. It is involved in the growth of thalamocortical projections and dendritic spine elimination. Previously, we characterized Pcdh10 haploinsufficient mice (Pcdh10 mice) and found male-specific social deficits and dark phase hypoactivity. Pcdh10 males exhibit increased dendritic spine density of immature morphology, decreased NMDAR expression, and decreased gamma synchronization in the basolateral amygdala (BLA). Here, we further characterize Pcdh10 mice by testing for fear memory, which relies on BLA function. We used both male and female Pcdh10 mice and their wild-type littermates at two ages, juvenile and adult, and in two learning paradigms, cued and contextual fear conditioning. We found that males at both ages and in both assays exhibited fear conditioning deficits, but females were only impaired as adults in the cued condition. These data are further evidence for male-specific alterations in BLA-related behaviors in Pcdh10 mice and suggest that these mice may be a useful model for dissecting male specific brain and behavioral phenotypes relevant to social and emotional behaviors.

摘要

PCDH10 是与自闭症谱系障碍相关的基因。它参与了丘脑皮质投射和树突棘消除的生长。此前,我们对 Pcdh10 杂合不足的小鼠(Pcdh10 小鼠)进行了特征描述,发现其存在雄性特有的社交缺陷和暗期活动减少。Pcdh10 雄性小鼠表现出不成熟形态的树突棘密度增加、NMDAR 表达减少以及基底外侧杏仁核(BLA)中的γ同步减少。在这里,我们通过测试恐惧记忆进一步对 Pcdh10 小鼠进行了特征描述,而恐惧记忆依赖于 BLA 的功能。我们使用了幼年期和成年期的雄性和雌性 Pcdh10 小鼠及其野生型同窝仔鼠,并在两种学习模式下,即条件性恐惧和情境性恐惧条件化中进行了测试。我们发现,无论是幼年期还是成年期的雄性小鼠,在两种检测中都表现出恐惧条件化缺陷,但只有成年雌性小鼠在条件性恐惧中受到损伤。这些数据进一步证明了 Pcdh10 小鼠的 BLA 相关行为存在雄性特异性改变,并表明这些小鼠可能是一个有用的模型,可用于剖析与社交和情绪行为相关的特定于雄性的大脑和行为表型。

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