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小脑蚓部失调导致的社会记忆缺陷。

Social memory deficit caused by dysregulation of the cerebellar vermis.

机构信息

Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN, 55812, USA.

Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore, Singapore.

出版信息

Nat Commun. 2023 Sep 26;14(1):6007. doi: 10.1038/s41467-023-41744-2.

Abstract

Social recognition memory (SRM) is a key determinant of social interactions. While the cerebellum emerges as an important region for social behavior, how cerebellar activity affects social functions remains unclear. We selectively increased the excitability of molecular layer interneurons (MLIs) to suppress Purkinje cell firing in the mouse cerebellar vermis. Chemogenetic perturbation of MLIs impaired SRM without affecting sociability, anxiety levels, motor coordination or object recognition. Optogenetic interference of MLIs during distinct phases of a social recognition test revealed the cerebellar engagement in the retrieval, but not encoding, of social information. c-Fos mapping after the social recognition test showed that cerebellar manipulation decreased brain-wide interregional correlations and altered network structure from medial prefrontal cortex and hippocampus-centered to amygdala-centered modules. Anatomical tracing demonstrated hierarchical projections from the central cerebellum to the social brain network integrating amygdalar connections. Our findings suggest that the cerebellum organizes the neural matrix necessary for SRM.

摘要

社会识别记忆 (SRM) 是社交互动的关键决定因素。虽然小脑作为一个重要的社交行为区域出现,但小脑活动如何影响社交功能尚不清楚。我们选择性地增加了分子层中间神经元 (MLI) 的兴奋性,以抑制小鼠小脑蚓部浦肯野细胞的放电。MLI 的化学遗传学干扰会损害 SRM,而不会影响社交能力、焦虑水平、运动协调或物体识别。在社会识别测试的不同阶段用光遗传学干扰 MLI 揭示了小脑在检索、而不是编码社会信息中的参与。社会识别测试后的 c-Fos 映射显示,小脑操作降低了大脑中区域间的相关性,并改变了网络结构,从以内侧前额叶皮层和海马为中心的模块转变为以杏仁核为中心的模块。解剖追踪显示,从中枢小脑到整合杏仁核连接的社交大脑网络的分层投射。我们的研究结果表明,小脑组织了社会识别记忆所需的神经基质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9af8/10522595/3ce8e5ab6917/41467_2023_41744_Fig1_HTML.jpg

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