All-trans retinoic acid induces synaptic plasticity in human cortical neurons
A defining feature of the brain is the ability of its synaptic contacts to adapt structurally and functionally in an experience-dependent manner. In the human cortex, however, direct experimental evidence for coordinated structural and functional synaptic adaptation is currently lacking. Here, we pr...
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eLife Sciences Publications Ltd
2021-03-01
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Online Access: | https://elifesciences.org/articles/63026 |
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author | Maximilian Lenz Pia Kruse Amelie Eichler Jakob Straehle Jürgen Beck Thomas Deller Andreas Vlachos |
author_facet | Maximilian Lenz Pia Kruse Amelie Eichler Jakob Straehle Jürgen Beck Thomas Deller Andreas Vlachos |
author_sort | Maximilian Lenz |
collection | DOAJ |
description | A defining feature of the brain is the ability of its synaptic contacts to adapt structurally and functionally in an experience-dependent manner. In the human cortex, however, direct experimental evidence for coordinated structural and functional synaptic adaptation is currently lacking. Here, we probed synaptic plasticity in human cortical slices using the vitamin A derivative all-trans retinoic acid (atRA), a putative treatment for neuropsychiatric disorders such as Alzheimer’s disease. Our experiments demonstrated that the excitatory synapses of superficial (layer 2/3) pyramidal neurons underwent coordinated structural and functional changes in the presence of atRA. These synaptic adaptations were accompanied by ultrastructural remodeling of the calcium-storing spine apparatus organelle and required mRNA translation. It was not observed in synaptopodin-deficient mice, which lack spine apparatus organelles. We conclude that atRA is a potent mediator of synaptic plasticity in the adult human cortex. |
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id | doaj.art-36c5ffc4f8d341739403e75f7c1f5ec0 |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-12T16:42:10Z |
publishDate | 2021-03-01 |
publisher | eLife Sciences Publications Ltd |
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spelling | doaj.art-36c5ffc4f8d341739403e75f7c1f5ec02022-12-22T03:24:43ZengeLife Sciences Publications LtdeLife2050-084X2021-03-011010.7554/eLife.63026All-trans retinoic acid induces synaptic plasticity in human cortical neuronsMaximilian Lenz0https://orcid.org/0000-0003-3147-4949Pia Kruse1https://orcid.org/0000-0002-1742-1608Amelie Eichler2https://orcid.org/0000-0001-7990-654XJakob Straehle3https://orcid.org/0000-0003-3063-8972Jürgen Beck4https://orcid.org/0000-0002-7687-6098Thomas Deller5https://orcid.org/0000-0002-3931-2947Andreas Vlachos6https://orcid.org/0000-0002-2646-3770Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, GermanyDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, GermanyDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, GermanyDepartment of Neurosurgery, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, GermanyDepartment of Neurosurgery, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Center for Basics in Neuromodulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, GermanyInstitute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Neuroscience Center, Goethe-University Frankfurt, Freiburg im Breisgau, GermanyDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Center for Basics in Neuromodulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; Center Brain Links Brain Tools, University of Freiburg, Freiburg im Breisgau, GermanyA defining feature of the brain is the ability of its synaptic contacts to adapt structurally and functionally in an experience-dependent manner. In the human cortex, however, direct experimental evidence for coordinated structural and functional synaptic adaptation is currently lacking. Here, we probed synaptic plasticity in human cortical slices using the vitamin A derivative all-trans retinoic acid (atRA), a putative treatment for neuropsychiatric disorders such as Alzheimer’s disease. Our experiments demonstrated that the excitatory synapses of superficial (layer 2/3) pyramidal neurons underwent coordinated structural and functional changes in the presence of atRA. These synaptic adaptations were accompanied by ultrastructural remodeling of the calcium-storing spine apparatus organelle and required mRNA translation. It was not observed in synaptopodin-deficient mice, which lack spine apparatus organelles. We conclude that atRA is a potent mediator of synaptic plasticity in the adult human cortex.https://elifesciences.org/articles/63026synaptopodinsynaptic plasticityhuman cortexvitamine Aretinoic acid |
spellingShingle | Maximilian Lenz Pia Kruse Amelie Eichler Jakob Straehle Jürgen Beck Thomas Deller Andreas Vlachos All-trans retinoic acid induces synaptic plasticity in human cortical neurons eLife synaptopodin synaptic plasticity human cortex vitamine A retinoic acid |
title | All-trans retinoic acid induces synaptic plasticity in human cortical neurons |
title_full | All-trans retinoic acid induces synaptic plasticity in human cortical neurons |
title_fullStr | All-trans retinoic acid induces synaptic plasticity in human cortical neurons |
title_full_unstemmed | All-trans retinoic acid induces synaptic plasticity in human cortical neurons |
title_short | All-trans retinoic acid induces synaptic plasticity in human cortical neurons |
title_sort | all trans retinoic acid induces synaptic plasticity in human cortical neurons |
topic | synaptopodin synaptic plasticity human cortex vitamine A retinoic acid |
url | https://elifesciences.org/articles/63026 |
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