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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Main Authors: Maximilian Lenz, Pia Kruse, Amelie Eichler, Jakob Straehle, Jürgen Beck, Thomas Deller, Andreas Vlachos
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-03-01
Series:eLife
Subjects:
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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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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AT amelieeichler alltransretinoicacidinducessynapticplasticityinhumancorticalneurons
AT jakobstraehle alltransretinoicacidinducessynapticplasticityinhumancorticalneurons
AT jurgenbeck alltransretinoicacidinducessynapticplasticityinhumancorticalneurons
AT thomasdeller alltransretinoicacidinducessynapticplasticityinhumancorticalneurons
AT andreasvlachos alltransretinoicacidinducessynapticplasticityinhumancorticalneurons