Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity
Summary: Homeostatic regulation of synapses is vital for nervous system function and key to understanding a range of neurological conditions. Synaptic homeostasis is proposed to operate over hours to counteract the destabilizing influence of long-term potentiation (LTP) and long-term depression (LTD...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724001670 |
| _version_ | 1797253973693956096 |
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| author | Simón(e) D. Sun Daniel Levenstein Boxing Li Nataniel Mandelberg Nicolas Chenouard Benjamin S. Suutari Sandrine Sanchez Guoling Tian John Rinzel György Buzsáki Richard W. Tsien |
| author_facet | Simón(e) D. Sun Daniel Levenstein Boxing Li Nataniel Mandelberg Nicolas Chenouard Benjamin S. Suutari Sandrine Sanchez Guoling Tian John Rinzel György Buzsáki Richard W. Tsien |
| author_sort | Simón(e) D. Sun |
| collection | DOAJ |
| description | Summary: Homeostatic regulation of synapses is vital for nervous system function and key to understanding a range of neurological conditions. Synaptic homeostasis is proposed to operate over hours to counteract the destabilizing influence of long-term potentiation (LTP) and long-term depression (LTD). The prevailing view holds that synaptic scaling is a slow first-order process that regulates postsynaptic glutamate receptors and fundamentally differs from LTP or LTD. Surprisingly, we find that the dynamics of scaling induced by neuronal inactivity are not exponential or monotonic, and the mechanism requires calcineurin and CaMKII, molecules dominant in LTD and LTP. Our quantitative model of these enzymes reconstructs the unexpected dynamics of homeostatic scaling and reveals how synapses can efficiently safeguard future capacity for synaptic plasticity. This mechanism of synaptic adaptation supports a broader set of homeostatic changes, including action potential autoregulation, and invites further inquiry into how such a mechanism varies in health and disease. |
| first_indexed | 2024-04-24T21:42:34Z |
| format | Article |
| id | doaj.art-5dbc5cec77d4460ab8a9a6266f3ea3b3 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-24T21:42:34Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5dbc5cec77d4460ab8a9a6266f3ea3b32024-03-21T05:36:34ZengElsevierCell Reports2211-12472024-04-01434113839Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivitySimón(e) D. Sun0Daniel Levenstein1Boxing Li2Nataniel Mandelberg3Nicolas Chenouard4Benjamin S. Suutari5Sandrine Sanchez6Guoling Tian7John Rinzel8György Buzsáki9Richard W. Tsien10Center for Neural Science, New York University, New York, NY 10003, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USACenter for Neural Science, New York University, New York, NY 10003, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, 3810 University Street, Montreal, QC, CanadaDepartment of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA; Neuroscience Program, Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine and the Fifth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510810, ChinaDepartment of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USADepartment of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA; Sorbonne Université, INSERM U1127, UMR CNRS 7225, Institut du Cerveau (ICM), 47 bld de l’hôpital, 75013 Paris, FranceCenter for Neural Science, New York University, New York, NY 10003, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USADepartment of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USADepartment of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USACenter for Neural Science, New York University, New York, NY 10003, USADepartment of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USACenter for Neural Science, New York University, New York, NY 10003, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA; Corresponding authorSummary: Homeostatic regulation of synapses is vital for nervous system function and key to understanding a range of neurological conditions. Synaptic homeostasis is proposed to operate over hours to counteract the destabilizing influence of long-term potentiation (LTP) and long-term depression (LTD). The prevailing view holds that synaptic scaling is a slow first-order process that regulates postsynaptic glutamate receptors and fundamentally differs from LTP or LTD. Surprisingly, we find that the dynamics of scaling induced by neuronal inactivity are not exponential or monotonic, and the mechanism requires calcineurin and CaMKII, molecules dominant in LTD and LTP. Our quantitative model of these enzymes reconstructs the unexpected dynamics of homeostatic scaling and reveals how synapses can efficiently safeguard future capacity for synaptic plasticity. This mechanism of synaptic adaptation supports a broader set of homeostatic changes, including action potential autoregulation, and invites further inquiry into how such a mechanism varies in health and disease.http://www.sciencedirect.com/science/article/pii/S2211124724001670synapsehomeostasissynaptic scalingHebbian plasticitylong-term potentiationlong-term depression |
| spellingShingle | Simón(e) D. Sun Daniel Levenstein Boxing Li Nataniel Mandelberg Nicolas Chenouard Benjamin S. Suutari Sandrine Sanchez Guoling Tian John Rinzel György Buzsáki Richard W. Tsien Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity Cell Reports synapse homeostasis synaptic scaling Hebbian plasticity long-term potentiation long-term depression |
| title | Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity |
| title_full | Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity |
| title_fullStr | Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity |
| title_full_unstemmed | Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity |
| title_short | Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity |
| title_sort | synaptic homeostasis transiently leverages hebbian mechanisms for a multiphasic response to inactivity |
| topic | synapse homeostasis synaptic scaling Hebbian plasticity long-term potentiation long-term depression |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724001670 |
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