High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans
The ability to learn progressively declines with age. Neural hyperactivity has been implicated in impairing cognitive plasticity with age, but the molecular mechanisms remain elusive. Here, we show that chronic excitation of the Caenorhabditis elegans O2-sensing neurons during ageing causes a rapid...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/59711 |
| _version_ | 1811236159875973120 |
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| author | Qiaochu Li Daniel-Cosmin Marcu Ottavia Palazzo Frances Turner Declan King Tara L Spires-Jones Melanie I Stefan Karl Emanuel Busch |
| author_facet | Qiaochu Li Daniel-Cosmin Marcu Ottavia Palazzo Frances Turner Declan King Tara L Spires-Jones Melanie I Stefan Karl Emanuel Busch |
| author_sort | Qiaochu Li |
| collection | DOAJ |
| description | The ability to learn progressively declines with age. Neural hyperactivity has been implicated in impairing cognitive plasticity with age, but the molecular mechanisms remain elusive. Here, we show that chronic excitation of the Caenorhabditis elegans O2-sensing neurons during ageing causes a rapid decline of experience-dependent plasticity in response to environmental O2 concentration, whereas sustaining lower activity of O2-sensing neurons retains plasticity with age. We demonstrate that neural activity alters the ageing trajectory in the transcriptome of O2-sensing neurons, and our data suggest that high-activity neurons redirect resources from maintaining plasticity to sustaining continuous firing. Sustaining plasticity with age requires the K+-dependent Na+/Ca2+ (NCKX) exchanger, whereas the decline of plasticity with age in high-activity neurons acts through calmodulin and the scaffold protein Kidins220. Our findings demonstrate directly that the activity of neurons alters neuronal homeostasis to govern the age-related decline of neural plasticity and throw light on the mechanisms involved. |
| first_indexed | 2024-04-12T12:04:10Z |
| format | Article |
| id | doaj.art-fa3083e036904e3e8216444c52f401e0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:04:10Z |
| publishDate | 2020-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fa3083e036904e3e8216444c52f401e02022-12-22T03:33:45ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.59711High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegansQiaochu Li0https://orcid.org/0000-0001-8032-9110Daniel-Cosmin Marcu1https://orcid.org/0000-0002-1006-3094Ottavia Palazzo2Frances Turner3Declan King4Tara L Spires-Jones5https://orcid.org/0000-0003-2530-0598Melanie I Stefan6https://orcid.org/0000-0002-6086-7357Karl Emanuel Busch7https://orcid.org/0000-0001-7886-3226Centre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, The University of Edinburgh, Edinburgh, United KingdomCentre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, The University of Edinburgh, Edinburgh, United KingdomCentre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, The University of Edinburgh, Edinburgh, United KingdomEdinburgh Genomics (Genome Science), Ashworth Laboratories, The University of Edinburgh, Edinburgh, United KingdomCentre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, The University of Edinburgh, Edinburgh, United Kingdom; United Kingdom Dementia Research Institute, The University of Edinburgh, Edinburgh, United KingdomCentre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, The University of Edinburgh, Edinburgh, United Kingdom; United Kingdom Dementia Research Institute, The University of Edinburgh, Edinburgh, United KingdomCentre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, The University of Edinburgh, Edinburgh, United Kingdom; ZJU-UoE Institute, Zhejiang University, Haining, ChinaCentre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, The University of Edinburgh, Edinburgh, United KingdomThe ability to learn progressively declines with age. Neural hyperactivity has been implicated in impairing cognitive plasticity with age, but the molecular mechanisms remain elusive. Here, we show that chronic excitation of the Caenorhabditis elegans O2-sensing neurons during ageing causes a rapid decline of experience-dependent plasticity in response to environmental O2 concentration, whereas sustaining lower activity of O2-sensing neurons retains plasticity with age. We demonstrate that neural activity alters the ageing trajectory in the transcriptome of O2-sensing neurons, and our data suggest that high-activity neurons redirect resources from maintaining plasticity to sustaining continuous firing. Sustaining plasticity with age requires the K+-dependent Na+/Ca2+ (NCKX) exchanger, whereas the decline of plasticity with age in high-activity neurons acts through calmodulin and the scaffold protein Kidins220. Our findings demonstrate directly that the activity of neurons alters neuronal homeostasis to govern the age-related decline of neural plasticity and throw light on the mechanisms involved.https://elifesciences.org/articles/59711experience-dependent plasticityneural ageingtranscriptomicsoxygen-sensing neuronsneuronal Ca2+ homeostasisplasticity decline |
| spellingShingle | Qiaochu Li Daniel-Cosmin Marcu Ottavia Palazzo Frances Turner Declan King Tara L Spires-Jones Melanie I Stefan Karl Emanuel Busch High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans eLife experience-dependent plasticity neural ageing transcriptomics oxygen-sensing neurons neuronal Ca2+ homeostasis plasticity decline |
| title | High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans |
| title_full | High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans |
| title_fullStr | High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans |
| title_full_unstemmed | High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans |
| title_short | High neural activity accelerates the decline of cognitive plasticity with age in Caenorhabditis elegans |
| title_sort | high neural activity accelerates the decline of cognitive plasticity with age in caenorhabditis elegans |
| topic | experience-dependent plasticity neural ageing transcriptomics oxygen-sensing neurons neuronal Ca2+ homeostasis plasticity decline |
| url | https://elifesciences.org/articles/59711 |
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