Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/D
Experience and activity refine cortical circuits through synapse elimination, but little is known about the activity patterns and downstream molecular mechanisms that mediate this process. We used optogenetics to drive individual mouse CA1 hippocampal neurons to fire in theta frequency bursts to und...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/26278 |
| _version_ | 1811253216730415104 |
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| author | Chia-Wei Chang Julia R Wilkerson Carly F Hale Jay R Gibson Kimberly M Huber |
| author_facet | Chia-Wei Chang Julia R Wilkerson Carly F Hale Jay R Gibson Kimberly M Huber |
| author_sort | Chia-Wei Chang |
| collection | DOAJ |
| description | Experience and activity refine cortical circuits through synapse elimination, but little is known about the activity patterns and downstream molecular mechanisms that mediate this process. We used optogenetics to drive individual mouse CA1 hippocampal neurons to fire in theta frequency bursts to understand how cell autonomous, postsynaptic activity leads to synapse elimination. Brief (1 hr) periods of postsynaptic bursting selectively depressed AMPA receptor (R) synaptic transmission, or silenced excitatory synapses, whereas more prolonged (24 hr) firing depressed both AMPAR and NMDAR EPSCs and eliminated spines, indicative of a synapse elimination. Both synapse silencing and elimination required de novo transcription, but only silencing required the activity-dependent transcription factors MEF2A/D. Burst firing induced MEF2A/D-dependent induction of the target gene Arc which contributed to synapse silencing and elimination. This work reveals new and distinct forms of activity and transcription-dependent synapse depression and suggests that these processes can occur independently. |
| first_indexed | 2024-04-12T16:46:36Z |
| format | Article |
| id | doaj.art-e59d3ffd427649028d0db9d4c3b414c7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:46:36Z |
| publishDate | 2017-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e59d3ffd427649028d0db9d4c3b414c72022-12-22T03:24:33ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.26278Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/DChia-Wei Chang0https://orcid.org/0000-0002-1011-6870Julia R Wilkerson1Carly F Hale2Jay R Gibson3Kimberly M Huber4https://orcid.org/0000-0002-7479-0661Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United StatesExperience and activity refine cortical circuits through synapse elimination, but little is known about the activity patterns and downstream molecular mechanisms that mediate this process. We used optogenetics to drive individual mouse CA1 hippocampal neurons to fire in theta frequency bursts to understand how cell autonomous, postsynaptic activity leads to synapse elimination. Brief (1 hr) periods of postsynaptic bursting selectively depressed AMPA receptor (R) synaptic transmission, or silenced excitatory synapses, whereas more prolonged (24 hr) firing depressed both AMPAR and NMDAR EPSCs and eliminated spines, indicative of a synapse elimination. Both synapse silencing and elimination required de novo transcription, but only silencing required the activity-dependent transcription factors MEF2A/D. Burst firing induced MEF2A/D-dependent induction of the target gene Arc which contributed to synapse silencing and elimination. This work reveals new and distinct forms of activity and transcription-dependent synapse depression and suggests that these processes can occur independently.https://elifesciences.org/articles/26278MEF2synapse silencingactivity-dependent synapse plasticity |
| spellingShingle | Chia-Wei Chang Julia R Wilkerson Carly F Hale Jay R Gibson Kimberly M Huber Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/D eLife MEF2 synapse silencing activity-dependent synapse plasticity |
| title | Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/D |
| title_full | Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/D |
| title_fullStr | Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/D |
| title_full_unstemmed | Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/D |
| title_short | Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/D |
| title_sort | distinct stages of synapse elimination are induced by burst firing of ca1 neurons and differentially require mef2a d |
| topic | MEF2 synapse silencing activity-dependent synapse plasticity |
| url | https://elifesciences.org/articles/26278 |
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