Functional alterations of the prefrontal circuit underlying cognitive aging in mice
Executive function is susceptible to aging. How aging impacts the circuit-level computations underlying executive function remains unclear. Using calcium imaging and optogenetic manipulation during memory-guided behavior, we show that working-memory coding and the relevant recurrent connectivity in...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/173002 |
| _version_ | 1824453461170716672 |
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| author | Chong, Huee Ru Ranjbar-Slamloo, Yadollah Ho, Malcolm Zheng Hao Ouyang, Xuan Kamigaki, Tsukasa |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Chong, Huee Ru Ranjbar-Slamloo, Yadollah Ho, Malcolm Zheng Hao Ouyang, Xuan Kamigaki, Tsukasa |
| author_sort | Chong, Huee Ru |
| collection | NTU |
| description | Executive function is susceptible to aging. How aging impacts the circuit-level computations underlying executive function remains unclear. Using calcium imaging and optogenetic manipulation during memory-guided behavior, we show that working-memory coding and the relevant recurrent connectivity in the mouse medial prefrontal cortex (mPFC) are altered as early as middle age. Population activity in the young adult mPFC exhibits dissociable yet overlapping patterns between tactile and auditory modalities, enabling crossmodal memory coding concurrent with modality-dependent coding. In middle age, however, crossmodal coding remarkably diminishes while modality-dependent coding persists, and both types of coding decay in advanced age. Resting-state functional connectivity, especially among memory-coding neurons, decreases already in middle age, suggesting deteriorated recurrent circuits for memory maintenance. Optogenetic inactivation reveals that the middle-aged mPFC exhibits heightened vulnerability to perturbations. These findings elucidate functional alterations of the prefrontal circuit that unfold in middle age and deteriorate further as a hallmark of cognitive aging. |
| first_indexed | 2024-10-01T08:00:41Z |
| format | Journal Article |
| id | ntu-10356/173002 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T08:00:41Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1730022024-05-03T02:36:49Z Functional alterations of the prefrontal circuit underlying cognitive aging in mice Chong, Huee Ru Ranjbar-Slamloo, Yadollah Ho, Malcolm Zheng Hao Ouyang, Xuan Kamigaki, Tsukasa Lee Kong Chian School of Medicine (LKCMedicine) Interdisciplinary Graduate School (IGS) Medicine, Health and Life Sciences Cognitive Aging Prefrontal Cortex Executive function is susceptible to aging. How aging impacts the circuit-level computations underlying executive function remains unclear. Using calcium imaging and optogenetic manipulation during memory-guided behavior, we show that working-memory coding and the relevant recurrent connectivity in the mouse medial prefrontal cortex (mPFC) are altered as early as middle age. Population activity in the young adult mPFC exhibits dissociable yet overlapping patterns between tactile and auditory modalities, enabling crossmodal memory coding concurrent with modality-dependent coding. In middle age, however, crossmodal coding remarkably diminishes while modality-dependent coding persists, and both types of coding decay in advanced age. Resting-state functional connectivity, especially among memory-coding neurons, decreases already in middle age, suggesting deteriorated recurrent circuits for memory maintenance. Optogenetic inactivation reveals that the middle-aged mPFC exhibits heightened vulnerability to perturbations. These findings elucidate functional alterations of the prefrontal circuit that unfold in middle age and deteriorate further as a hallmark of cognitive aging. Ministry of Education (MOE) Nanyang Technological University Published version This research is supported by the Ministry of Education, Singapore, under its MOE AcRF Tier 2 Award MOE-T2EP30220-0003, MOE AcRF Tier 1 Award RS01/19, MOE AcRF Tier 1 Award RG19/21, and by the Lee Kong Chian School of Medicine - Ministry of Education Start-Up Grant for T.K. 2024-01-08T08:21:38Z 2024-01-08T08:21:38Z 2023 Journal Article Chong, H. R., Ranjbar-Slamloo, Y., Ho, M. Z. H., Ouyang, X. & Kamigaki, T. (2023). Functional alterations of the prefrontal circuit underlying cognitive aging in mice. Nature Communications, 14(1), 7254-. https://dx.doi.org/10.1038/s41467-023-43142-0 2041-1723 https://hdl.handle.net/10356/173002 10.1038/s41467-023-43142-0 14 2-s2.0-85176110685 1 14 7254 en MOE-T2EP30220-0003 RS01/19 RG19/21 Nature Communications doi:10.21979/N9/O0JPLP © 2023 The Author(s). 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Cognitive Aging Prefrontal Cortex Chong, Huee Ru Ranjbar-Slamloo, Yadollah Ho, Malcolm Zheng Hao Ouyang, Xuan Kamigaki, Tsukasa Functional alterations of the prefrontal circuit underlying cognitive aging in mice |
| title | Functional alterations of the prefrontal circuit underlying cognitive aging in mice |
| title_full | Functional alterations of the prefrontal circuit underlying cognitive aging in mice |
| title_fullStr | Functional alterations of the prefrontal circuit underlying cognitive aging in mice |
| title_full_unstemmed | Functional alterations of the prefrontal circuit underlying cognitive aging in mice |
| title_short | Functional alterations of the prefrontal circuit underlying cognitive aging in mice |
| title_sort | functional alterations of the prefrontal circuit underlying cognitive aging in mice |
| topic | Medicine, Health and Life Sciences Cognitive Aging Prefrontal Cortex |
| url | https://hdl.handle.net/10356/173002 |
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