All-trans retinoic acid induces synaptic plasticity in human cortical neurons

  • Maximilian Lenz
    Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
  • Pia Kruse
    Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
  • Amelie Eichler
    Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
  • Jakob Straehle
    Department of Neurosurgery, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
  • Jürgen Beck
    Department of Neurosurgery, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
  • Thomas Deller
    Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Neuroscience Center, Goethe-University Frankfurt, Freiburg im Breisgau, Germany
  • Andreas Vlachos
    Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany

抄録

<jats:p>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.</jats:p>

収録刊行物

  • eLife

    eLife 10 e63026-, 2021-03-30

    eLife Sciences Publications, Ltd

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