Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice
© 2020, The Author(s). Many neurodevelopmental disorders are characterized by impaired functional synaptic plasticity and abnormal dendritic spine morphology, but little is known about how these are related. Previous work in the Fmr1-/y mouse model of fragile X (FX) suggests that increased constitut...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/135318 |
| _version_ | 1811073334665805824 |
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| author | Thomazeau, Aurore Bosch, Miquel Essayan-Perez, Sofia Barnes, Stephanie A De Jesus-Cortes, Hector Bear, Mark F |
| author_facet | Thomazeau, Aurore Bosch, Miquel Essayan-Perez, Sofia Barnes, Stephanie A De Jesus-Cortes, Hector Bear, Mark F |
| author_sort | Thomazeau, Aurore |
| collection | MIT |
| description | © 2020, The Author(s). Many neurodevelopmental disorders are characterized by impaired functional synaptic plasticity and abnormal dendritic spine morphology, but little is known about how these are related. Previous work in the Fmr1-/y mouse model of fragile X (FX) suggests that increased constitutive dendritic protein synthesis yields exaggerated mGluR5-dependent long-term synaptic depression (LTD) in area CA1 of the hippocampus, but an effect on spine structural plasticity remains to be determined. In the current study, we used simultaneous electrophysiology and time-lapse two photon imaging to examine how spines change their structure during LTD induced by activation of mGluRs or NMDA receptors (NMDARs), and how this plasticity is altered in Fmr1-/y mice. We were surprised to find that mGluR activation causes LTD and AMPA receptor internalization, but no spine shrinkage in either wildtype or Fmr1-/y mice. In contrast, NMDAR activation caused spine shrinkage as well as LTD in both genotypes. Spine shrinkage was initiated by non-ionotropic (metabotropic) signaling through NMDARs, and in wild-type mice this structural plasticity required activation of mTORC1 and new protein synthesis. In striking contrast, NMDA-induced spine plasticity in Fmr1-/y mice was no longer dependent on acute activation of mTORC1 or de novo protein synthesis. These findings reveal that the structural consequences of mGluR and metabotropic NMDAR activation differ, and that a brake on spine structural plasticity, normally provided by mTORC1 regulation of protein synthesis, is absent in FX. Increased constitutive protein synthesis in FX appears to modify functional and structural plasticity induced through different glutamate receptors. |
| first_indexed | 2024-09-23T09:31:26Z |
| format | Article |
| id | mit-1721.1/135318 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:31:26Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1353182021-10-28T04:44:14Z Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice Thomazeau, Aurore Bosch, Miquel Essayan-Perez, Sofia Barnes, Stephanie A De Jesus-Cortes, Hector Bear, Mark F © 2020, The Author(s). Many neurodevelopmental disorders are characterized by impaired functional synaptic plasticity and abnormal dendritic spine morphology, but little is known about how these are related. Previous work in the Fmr1-/y mouse model of fragile X (FX) suggests that increased constitutive dendritic protein synthesis yields exaggerated mGluR5-dependent long-term synaptic depression (LTD) in area CA1 of the hippocampus, but an effect on spine structural plasticity remains to be determined. In the current study, we used simultaneous electrophysiology and time-lapse two photon imaging to examine how spines change their structure during LTD induced by activation of mGluRs or NMDA receptors (NMDARs), and how this plasticity is altered in Fmr1-/y mice. We were surprised to find that mGluR activation causes LTD and AMPA receptor internalization, but no spine shrinkage in either wildtype or Fmr1-/y mice. In contrast, NMDAR activation caused spine shrinkage as well as LTD in both genotypes. Spine shrinkage was initiated by non-ionotropic (metabotropic) signaling through NMDARs, and in wild-type mice this structural plasticity required activation of mTORC1 and new protein synthesis. In striking contrast, NMDA-induced spine plasticity in Fmr1-/y mice was no longer dependent on acute activation of mTORC1 or de novo protein synthesis. These findings reveal that the structural consequences of mGluR and metabotropic NMDAR activation differ, and that a brake on spine structural plasticity, normally provided by mTORC1 regulation of protein synthesis, is absent in FX. Increased constitutive protein synthesis in FX appears to modify functional and structural plasticity induced through different glutamate receptors. 2021-10-27T20:22:56Z 2021-10-27T20:22:56Z 2020 2021-03-11T18:16:13Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135318 en 10.1038/S41380-020-0821-6 Molecular Psychiatry Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Thomazeau, Aurore Bosch, Miquel Essayan-Perez, Sofia Barnes, Stephanie A De Jesus-Cortes, Hector Bear, Mark F Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice |
| title | Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice |
| title_full | Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice |
| title_fullStr | Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice |
| title_full_unstemmed | Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice |
| title_short | Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice |
| title_sort | dissociation of functional and structural plasticity of dendritic spines during nmdar and mglur dependent long term synaptic depression in wild type and fragile x model mice |
| url | https://hdl.handle.net/1721.1/135318 |
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