Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model
Summary: In Alzheimer’s disease (AD), network hyperexcitability is frequently observed and associated with subsequent cognitive impairment. Dysfunction of inhibitory interneurons (INs) is thought to be one of the key biological mechanisms of hyperexcitability. However, it is still unknown how INs ar...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223004194 |
| _version_ | 1797867593885810688 |
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| author | Takehiro Kudo Hiroyuki Takuwa Manami Takahashi Takuya Urushihata Masafumi Shimojo Kazuaki Sampei Mitsugu Yamanaka Yutaka Tomita Naruhiko Sahara Tetsuya Suhara Makoto Higuchi |
| author_facet | Takehiro Kudo Hiroyuki Takuwa Manami Takahashi Takuya Urushihata Masafumi Shimojo Kazuaki Sampei Mitsugu Yamanaka Yutaka Tomita Naruhiko Sahara Tetsuya Suhara Makoto Higuchi |
| author_sort | Takehiro Kudo |
| collection | DOAJ |
| description | Summary: In Alzheimer’s disease (AD), network hyperexcitability is frequently observed and associated with subsequent cognitive impairment. Dysfunction of inhibitory interneurons (INs) is thought to be one of the key biological mechanisms of hyperexcitability. However, it is still unknown how INs are functionally affected in tau pathology, which is a major pathology in AD. To clarify this, we evaluated the neuronal activity of cortical INs in 6-month-old rTg4510 mice, a model of tauopathy. Calcium imaging with mDlx enhancer-driven labeling revealed that neuronal activity in INs was decreased in rTg4510 mice. In the patch clamp recording, the firing properties of fast-spiking INs were altered so as to reduce their activity in rTg4510 mice. In parallel with microglial activation, perineuronal nets around parvalbumin-positive INs were partially disrupted in rTg4510 mice. Taken together, our data indicate that the excitability of cortical fast-spiking INs is decreased, possibly because of the disruption of perineuronal nets. |
| first_indexed | 2024-04-09T23:42:41Z |
| format | Article |
| id | doaj.art-5f7c5b6f3d714688a91843c1e22d0942 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T23:42:41Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-5f7c5b6f3d714688a91843c1e22d09422023-03-18T04:42:33ZengElsevieriScience2589-00422023-04-01264106342Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse modelTakehiro Kudo0Hiroyuki Takuwa1Manami Takahashi2Takuya Urushihata3Masafumi Shimojo4Kazuaki Sampei5Mitsugu Yamanaka6Yutaka Tomita7Naruhiko Sahara8Tetsuya Suhara9Makoto Higuchi10Sumitomo Pharma Co., Ltd., Osaka, Japan; Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Collaborative Chairs Quantum Life Science·and Molecular Imaging, Tohoku University, Sendai, JapanDepartment of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Neuromapping and Neuromodulation Group, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Corresponding authorDepartment of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Neuromapping and Neuromodulation Group, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanDepartment of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanDepartment of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanSumitomo Pharma Co., Ltd., Osaka, JapanSumitomo Pharma Co., Ltd., Osaka, JapanDepartment of Neurology, Keio University School of Medicine, Tokyo, JapanDepartment of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanDepartment of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Neuromapping and Neuromodulation Group, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, JapanDepartment of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Corresponding authorSummary: In Alzheimer’s disease (AD), network hyperexcitability is frequently observed and associated with subsequent cognitive impairment. Dysfunction of inhibitory interneurons (INs) is thought to be one of the key biological mechanisms of hyperexcitability. However, it is still unknown how INs are functionally affected in tau pathology, which is a major pathology in AD. To clarify this, we evaluated the neuronal activity of cortical INs in 6-month-old rTg4510 mice, a model of tauopathy. Calcium imaging with mDlx enhancer-driven labeling revealed that neuronal activity in INs was decreased in rTg4510 mice. In the patch clamp recording, the firing properties of fast-spiking INs were altered so as to reduce their activity in rTg4510 mice. In parallel with microglial activation, perineuronal nets around parvalbumin-positive INs were partially disrupted in rTg4510 mice. Taken together, our data indicate that the excitability of cortical fast-spiking INs is decreased, possibly because of the disruption of perineuronal nets.http://www.sciencedirect.com/science/article/pii/S2589004223004194Molecular neuroscienceCellular neuroscience |
| spellingShingle | Takehiro Kudo Hiroyuki Takuwa Manami Takahashi Takuya Urushihata Masafumi Shimojo Kazuaki Sampei Mitsugu Yamanaka Yutaka Tomita Naruhiko Sahara Tetsuya Suhara Makoto Higuchi Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model iScience Molecular neuroscience Cellular neuroscience |
| title | Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model |
| title_full | Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model |
| title_fullStr | Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model |
| title_full_unstemmed | Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model |
| title_short | Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model |
| title_sort | selective dysfunction of fast spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model |
| topic | Molecular neuroscience Cellular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223004194 |
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