SynEM, automated synapse detection for connectomics

  1. Benedikt Staffler
  2. Manuel Berning
  3. Kevin M Boergens
  4. Anjali Gour
  5. Patrick van der Smagt
  6. Moritz Helmstaedter  Is a corresponding author
  1. Max Planck Institute for Brain Research, Germany
  2. Volkswagen Group, Germany

Abstract

Nerve tissue contains a high density of chemical synapses, about 1 per µm3 in the mammalian cerebral cortex. Thus, even for small blocks of nerve tissue, dense connectomic mapping requires the identification of millions to billions of synapses. While the focus of connectomic data analysis has been on neurite reconstruction, synapse detection becomes limiting when datasets grow in size and dense mapping is required. Here, we report SynEM, a method for automated detection of synapses from conventionally en-bloc stained 3D electron microscopy image stacks. The approach is based on a segmentation of the image data and focuses on classifying borders between neuronal processes as synaptic or non-synaptic. SynEM yields 97% precision and recall in binary cortical connectomes with no user interaction. It scales to large volumes of cortical neuropil, plausibly even whole-brain datasets. SynEM removes the burden of manual synapse annotation for large densely mapped connectomes.

Data availability

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Benedikt Staffler

    Department of Connectomics, Max Planck Institute for Brain Research, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Manuel Berning

    Department of Connectomics, Max Planck Institute for Brain Research, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3679-8363
  3. Kevin M Boergens

    Department of Connectomics, Max Planck Institute for Brain Research, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Anjali Gour

    Department of Connectomics, Max Planck Institute for Brain Research, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Patrick van der Smagt

    Data Lab, Volkswagen Group, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Moritz Helmstaedter

    Department of Connectomics, Max Planck Institute for Brain Research, Frankfurt, Germany
    For correspondence
    mh@brain.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7973-0767

Funding

Max-Planck Society (Open access funding)

  • Benedikt Staffler
  • Manuel Berning
  • Kevin M Boergens
  • Anjali Gour
  • Moritz Helmstaedter

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

Ethics

Animal experimentation: All animal experiments were performed in accordance with the guidelines for the Use of Laboratory Animals of the Max Planck Society and approved by the local authorities Regierungspräsidium Oberbayern, AZ 55.2-1-54-2532.3-103-12.

Copyright

© 2017, Staffler 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

  • 3,961
    views
  • 613
    downloads
  • 59
    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. Benedikt Staffler
  2. Manuel Berning
  3. Kevin M Boergens
  4. Anjali Gour
  5. Patrick van der Smagt
  6. Moritz Helmstaedter
(2017)
SynEM, automated synapse detection for connectomics
eLife 6:e26414.
https://doi.org/10.7554/eLife.26414

Share this article

https://doi.org/10.7554/eLife.26414

Further reading

    1. Neuroscience
    Cameron T Ellis, Tristan S Yates ... Nicholas Turk-Browne
    Research Article

    Studying infant minds with movies is a promising way to increase engagement relative to traditional tasks. However, the spatial specificity and functional significance of movie-evoked activity in infants remains unclear. Here, we investigated what movies can reveal about the organization of the infant visual system. We collected fMRI data from 15 awake infants and toddlers aged 5–23 months who attentively watched a movie. The activity evoked by the movie reflected the functional profile of visual areas. Namely, homotopic areas from the two hemispheres responded similarly to the movie, whereas distinct areas responded dissimilarly, especially across dorsal and ventral visual cortex. Moreover, visual maps that typically require time-intensive and complicated retinotopic mapping could be predicted, albeit imprecisely, from movie-evoked activity in both data-driven analyses (i.e. independent component analysis) at the individual level and by using functional alignment into a common low-dimensional embedding to generalize across participants. These results suggest that the infant visual system is already structured to process dynamic, naturalistic information and that fine-grained cortical organization can be discovered from movie data.

    1. Neuroscience
    Gaqi Tu, Peiying Wen ... Kaori Takehara-Nishiuchi
    Research Article

    Outcomes can vary even when choices are repeated. Such ambiguity necessitates adjusting how much to learn from each outcome by tracking its variability. The medial prefrontal cortex (mPFC) has been reported to signal the expected outcome and its discrepancy from the actual outcome (prediction error), two variables essential for controlling the learning rate. However, the source of signals that shape these coding properties remains unknown. Here, we investigated the contribution of cholinergic projections from the basal forebrain because they carry precisely timed signals about outcomes. One-photon calcium imaging revealed that as mice learned different probabilities of threat occurrence on two paths, some mPFC cells responded to threats on one of the paths, while other cells gained responses to threat omission. These threat- and omission-evoked responses were scaled to the unexpectedness of outcomes, some exhibiting a reversal in response direction when encountering surprising threats as opposed to surprising omissions. This selectivity for signed prediction errors was enhanced by optogenetic stimulation of local cholinergic terminals during threats. The enhanced threat-evoked cholinergic signals also made mice erroneously abandon the correct choice after a single threat that violated expectations, thereby decoupling their path choice from the history of threat occurrence on each path. Thus, acetylcholine modulates the encoding of surprising outcomes in the mPFC to control how much they dictate future decisions.