Ultrastructural heterogeneity of layer 4 excitatory synaptic boutons in the adult human temporal lobe neocortex

  1. Rachida Yakoubi
  2. Astrid Rollenhagen
  3. Marec von Lehe
  4. Dorothea Miller
  5. Bernd Walkenfort
  6. Mike Hasenberg
  7. Kurt Sätzler
  8. Joachim HR Lübke  Is a corresponding author
  1. Research Centre Jülich GmbH, Germany
  2. Brandenburg Medical School, Germany
  3. University Hospital/Knappschaftskrankenhaus Bochum, Germany
  4. University Hospital Essen, Germany
  5. University of Ulster, United Kingdom

Abstract

Synapses are fundamental building blocks controlling and modulating the 'behavior' of brain networks. How their structural composition, most notably their quantitative morphology underlie their computational properties remains rather unclear, particularly in humans. Here, excitatory synaptic boutons (SBs) in layer 4 (L4) of the temporal lobe neocortex (TLN) were quantitatively investigated. Biopsies from epilepsy surgery were used for fine-scale and tomographic electron microscopy (EM) to generate 3D-reconstructions of SBs. Particularly, the size of active zones (AZs) and that of the three functionally defined pools of synaptic vesicles (SVs) were quantified. SBs were comparatively small (~2.50 μm2), with a single AZ (~0.13 µm2); preferentially established on spines. SBs had a total pool of ~1800 SVs with strikingly large readily releasable (~ 20), recycling (~ 80) and resting pools (~850). Thus, human L4 SBs may act as 'amplifiers' of signals from the sensory periphery, integrate, synchronize and modulate intra- and extracortical synaptic activity.

Data availability

Original datasets were already uploaded as source files since there is no appropriate domain-specific archive for our data.

Article and author information

Author details

  1. Rachida Yakoubi

    Institute of Neuroscience and Medicine INM-10, Research Centre Jülich GmbH, Jülich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Astrid Rollenhagen

    Institute of Neuroscience and Medicine INM-10, Research Centre Jülich GmbH, Jülich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Marec von Lehe

    Department of Neurosurgery, Brandenburg Medical School, Neuruppin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Dorothea Miller

    Department of Neurosurgery, University Hospital/Knappschaftskrankenhaus Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Bernd Walkenfort

    Medical Research Centre, IMCES Electron Microscopy Unit (EMU), University Hospital Essen, Essen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Mike Hasenberg

    Medical Research Centre, IMCES Electron Microscopy Unit (EMU), University Hospital Essen, Essen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Kurt Sätzler

    School of Biomedical Sciences, University of Ulster, Londonderry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Joachim HR Lübke

    Institute of Neuroscience and Medicine-INM-10, Research Centre Jülich GmbH, Jülich, Germany
    For correspondence
    j.luebke@fz-juelich.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4086-3199

Funding

Deutscher Akademischer Austauschdienst

  • Rachida Yakoubi

Deutscher Akademischer Austauschdienst

  • Joachim HR Lübke

Helmholtz-Gemeinschaft (Research Grant)

  • Joachim HR Lübke

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The consent of the patients was obtained and all experimental procedures were approved by the Ethical Committees of the Rheinische Friedrich-Wilhelms-University/University Hospital Bonn (ethic votum of the Medical Faculty to Prof. Dr. med. Johannes Schramm and Prof. Dr. rer. nat. Joachim Lübke, Nr. 146/11), and the University of Bochum (ethic votum of the Medical Faculty to PD Dr. med. Marec von Lehe and Prof. Dr. rer. nat. Joachim Lübke, Reg. No. 5190-14-15; ethic votum of the Medical Faculty to Dr. med. Dorothea Miller and Prof. Dr. rer. nat. Joachim Lübke, Reg. No. 17-6199-BR), and the EU directive (2015/565/EC and 2015/566/EC) concerning working with human tissue.

Copyright

© 2019, Yakoubi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,639
    views
  • 253
    downloads
  • 37
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Rachida Yakoubi
  2. Astrid Rollenhagen
  3. Marec von Lehe
  4. Dorothea Miller
  5. Bernd Walkenfort
  6. Mike Hasenberg
  7. Kurt Sätzler
  8. Joachim HR Lübke
(2019)
Ultrastructural heterogeneity of layer 4 excitatory synaptic boutons in the adult human temporal lobe neocortex
eLife 8:e48373.
https://doi.org/10.7554/eLife.48373

Share this article

https://doi.org/10.7554/eLife.48373

Further reading

    1. Neuroscience
    Sam E Benezra, Kripa B Patel ... Randy M Bruno
    Research Article

    Learning alters cortical representations and improves perception. Apical tuft dendrites in cortical layer 1, which are unique in their connectivity and biophysical properties, may be a key site of learning-induced plasticity. We used both two-photon and SCAPE microscopy to longitudinally track tuft-wide calcium spikes in apical dendrites of layer 5 pyramidal neurons in barrel cortex as mice learned a tactile behavior. Mice were trained to discriminate two orthogonal directions of whisker stimulation. Reinforcement learning, but not repeated stimulus exposure, enhanced tuft selectivity for both directions equally, even though only one was associated with reward. Selective tufts emerged from initially unresponsive or low-selectivity populations. Animal movement and choice did not account for changes in stimulus selectivity. Enhanced selectivity persisted even after rewards were removed and animals ceased performing the task. We conclude that learning produces long-lasting realignment of apical dendrite tuft responses to behaviorally relevant dimensions of a task.

    1. Neuroscience
    Rongxin Fang, Aaron Halpern ... Xiaowei Zhuang
    Tools and Resources

    Multiplexed error-robust fluorescence in situ hybridization (MERFISH) allows genome-scale imaging of RNAs in individual cells in intact tissues. To date, MERFISH has been applied to image thin-tissue samples of ~10 µm thickness. Here, we present a thick-tissue three-dimensional (3D) MERFISH imaging method, which uses confocal microscopy for optical sectioning, deep learning for increasing imaging speed and quality, as well as sample preparation and imaging protocol optimized for thick samples. We demonstrated 3D MERFISH on mouse brain tissue sections of up to 200 µm thickness with high detection efficiency and accuracy. We anticipate that 3D thick-tissue MERFISH imaging will broaden the scope of questions that can be addressed by spatial genomics.