Social memory deficit caused by dysregulation of the cerebellar vermis
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...
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sg-ntu-dr.10356-1738942024-03-10T15:37:59Z Social memory deficit caused by dysregulation of the cerebellar vermis Chao, Owen Y. Pathak, Salil Saurav Zhang, Hao Augustine, George James Christie, Jason M. Kikuchi, Chikako Taniguchi, Hiroki Yang, Yi-Mei Lee Kong Chian School of Medicine (LKCMedicine) Medicine, Health and Life Sciences Cerebellar Vermis Memory disorder 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. Ministry of Education (MOE) Published version This study was supported by the National Institutes of Health (NIH) grants R15 NS112964 and R01 MH129300 to Y.M.Y. and R01 NS112289 to J.M.C., the Singapore Ministry of Education grant MOE2017-T3-1-002 to G.J.A., the Brain & Behavior Research Foundation Young Investigator grant to O.Y.C., and the Winston and Maxine Wallin Neuroscience Discovery Fund to YMY. AAV1-hSyn-Cre and AAVrg-hSyn-EGFP were purchased from Addgene (gifts from Drs. James M Wilson and Bryan Roth). 2024-03-05T04:24:44Z 2024-03-05T04:24:44Z 2023 Journal Article Chao, O. Y., Pathak, S. S., Zhang, H., Augustine, G. J., Christie, J. M., Kikuchi, C., Taniguchi, H. & Yang, Y. (2023). Social memory deficit caused by dysregulation of the cerebellar vermis. Nature Communications, 14(1), 6007-. https://dx.doi.org/10.1038/s41467-023-41744-2 2041-1723 https://hdl.handle.net/10356/173894 10.1038/s41467-023-41744-2 37752149 2-s2.0-85172201124 1 14 6007 en MOE2017-T3-1-002 Nature Communications © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf |
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Medicine, Health and Life Sciences Cerebellar Vermis Memory disorder Chao, Owen Y. Pathak, Salil Saurav Zhang, Hao Augustine, George James Christie, Jason M. Kikuchi, Chikako Taniguchi, Hiroki Yang, Yi-Mei Social memory deficit caused by dysregulation of the cerebellar vermis |
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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. |
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Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Chao, Owen Y. Pathak, Salil Saurav Zhang, Hao Augustine, George James Christie, Jason M. Kikuchi, Chikako Taniguchi, Hiroki Yang, Yi-Mei |
format |
Article |
author |
Chao, Owen Y. Pathak, Salil Saurav Zhang, Hao Augustine, George James Christie, Jason M. Kikuchi, Chikako Taniguchi, Hiroki Yang, Yi-Mei |
author_sort |
Chao, Owen Y. |
title |
Social memory deficit caused by dysregulation of the cerebellar vermis |
title_short |
Social memory deficit caused by dysregulation of the cerebellar vermis |
title_full |
Social memory deficit caused by dysregulation of the cerebellar vermis |
title_fullStr |
Social memory deficit caused by dysregulation of the cerebellar vermis |
title_full_unstemmed |
Social memory deficit caused by dysregulation of the cerebellar vermis |
title_sort |
social memory deficit caused by dysregulation of the cerebellar vermis |
publishDate |
2024 |
url |
https://hdl.handle.net/10356/173894 |
_version_ |
1794549449117138944 |