Activity-dependent synapse elimination requires caspase-3 activation
During brain development, synapses are initially formed in excess and are later eliminated in an activity-dependent manner. Weak synapses are preferentially removed, but the mechanism linking neuronal activity to synapse removal is unclear. Here, we show that, in the developing mouse visual pathway,...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/101779 |
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| _version_ | 1850159686309904384 |
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| author | Zhou Yu Andrian Gutu Namsoo Kim Erin K O'Shea |
| author_facet | Zhou Yu Andrian Gutu Namsoo Kim Erin K O'Shea |
| author_sort | Zhou Yu |
| collection | DOAJ |
| description | During brain development, synapses are initially formed in excess and are later eliminated in an activity-dependent manner. Weak synapses are preferentially removed, but the mechanism linking neuronal activity to synapse removal is unclear. Here, we show that, in the developing mouse visual pathway, inhibiting synaptic transmission induces postsynaptic activation of caspase-3. Caspase-3 deficiency results in defects in synapse elimination driven by both spontaneous and experience-dependent neural activity. Notably, caspase-3 deficiency blocks activity-dependent synapse elimination, as evidenced by reduced engulfment of inactive synapses by microglia. Furthermore, in a mouse model of Alzheimer’s disease, caspase-3 deficiency protects against synapse loss induced by amyloid-β deposition. Our results reveal caspase-3 activation as a key step in activity-dependent synapse elimination during development and synapse loss in neurodegeneration. |
| format | Article |
| id | doaj-art-3ac6b62f8586482f99bb5c3a2ced4777 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-3ac6b62f8586482f99bb5c3a2ced47772025-08-20T02:23:27ZengeLife Sciences Publications LtdeLife2050-084X2025-06-011310.7554/eLife.101779Activity-dependent synapse elimination requires caspase-3 activationZhou Yu0https://orcid.org/0000-0003-3213-4583Andrian Gutu1https://orcid.org/0000-0002-5804-1978Namsoo Kim2Erin K O'Shea3https://orcid.org/0000-0002-2649-1018Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesDuring brain development, synapses are initially formed in excess and are later eliminated in an activity-dependent manner. Weak synapses are preferentially removed, but the mechanism linking neuronal activity to synapse removal is unclear. Here, we show that, in the developing mouse visual pathway, inhibiting synaptic transmission induces postsynaptic activation of caspase-3. Caspase-3 deficiency results in defects in synapse elimination driven by both spontaneous and experience-dependent neural activity. Notably, caspase-3 deficiency blocks activity-dependent synapse elimination, as evidenced by reduced engulfment of inactive synapses by microglia. Furthermore, in a mouse model of Alzheimer’s disease, caspase-3 deficiency protects against synapse loss induced by amyloid-β deposition. Our results reveal caspase-3 activation as a key step in activity-dependent synapse elimination during development and synapse loss in neurodegeneration.https://elifesciences.org/articles/101779synapse eliminationsynaptic activitycaspase-3microglia |
| spellingShingle | Zhou Yu Andrian Gutu Namsoo Kim Erin K O'Shea Activity-dependent synapse elimination requires caspase-3 activation eLife synapse elimination synaptic activity caspase-3 microglia |
| title | Activity-dependent synapse elimination requires caspase-3 activation |
| title_full | Activity-dependent synapse elimination requires caspase-3 activation |
| title_fullStr | Activity-dependent synapse elimination requires caspase-3 activation |
| title_full_unstemmed | Activity-dependent synapse elimination requires caspase-3 activation |
| title_short | Activity-dependent synapse elimination requires caspase-3 activation |
| title_sort | activity dependent synapse elimination requires caspase 3 activation |
| topic | synapse elimination synaptic activity caspase-3 microglia |
| url | https://elifesciences.org/articles/101779 |
| work_keys_str_mv | AT zhouyu activitydependentsynapseeliminationrequirescaspase3activation AT andriangutu activitydependentsynapseeliminationrequirescaspase3activation AT namsookim activitydependentsynapseeliminationrequirescaspase3activation AT erinkoshea activitydependentsynapseeliminationrequirescaspase3activation |