Project

Back to overview

Neural Circuit Reconstruction

English title Neural Circuit Reconstruction
Applicant Hahnloser Richard
Number 130470
Funding scheme Sinergia
Research institution Institut für Neuroinformatik Universität Zürich Irchel und ETH Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurophysiology and Brain Research
Start/End 01.01.2011 - 31.12.2014
Approved amount 1'500'000.00
Show all

All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Information Technology

Keywords (14)

Electron microscopy; Light microscopy; Computer vision; Histology; Image processing; Connectome; Brain wiring; Synapse; Circuit; Neural network; Brain; Network; segmentation; algorithm

Lay Summary (English)

Lead
Lay summary
Understanding structure-function relationships is one of the most successful strategies in biology that in the context of neuroscience requires exhaustive measurements of connectivity between neurons to extract the topology of synaptic interactions in neuronal circuits. This goal is considered "one of the holy grails of Neuroscience" since it would pave the way for a systematic analysis of neuronal circuit function based on computational modeling.The recent development of 3-D electron microscopy (3DEM) techniques allows the ultrastructural analysis of biological tissues throughout large volumes (up to a few hundred micrometers in each dimension). Although 3DEM has an enormous potential for advancing our understanding of brain function in health and disease, its biomedical application is currently impeded by the lack of accessory technologies, particularly informatics tools for the automated analysis of large and complex sets of image data. Automated processing and interpretation of light and electron microscopy images represents an extremely challenging problem even when supervision information is provided. New computational tools must be developed for the registration of light and electron microscopy images, for annotating features to identify synapses and other subcellular structures, for classifying image voxels to aid volumetric image segmentation, and for tracing of neuron morphologies based on local and global information. Our project is interdisciplinary and we are composed of neurobiologists and computer vision scientists. We are divided into groups that work on different animal models and pursue different electron microscopy approaches.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Pyramidal cells make specific connections onto smooth (GABAergic) cells in mouse visual cortex.
Bopp R Macarico Da Costa N Kampa BM Martin KAC Roth MM (2014), Pyramidal cells make specific connections onto smooth (GABAergic) cells in mouse visual cortex., in PLoS Biology, 12(8), 1.
Anisotropic ssTEM Image Segmentation Using Dense Correspondence across Sections
Dmitry Laptev Alexander Vezhnevets Sarvesh Dwivedi Joachim M. Buhmann (2012), Anisotropic ssTEM Image Segmentation Using Dense Correspondence across Sections, in Medical Image Computing and Computer-Assisted Intervention – MICCAI 2012, Nice, FranceSpringer Publishing, New York, US.
Efficient Automatic 3D-Reconstruction of Branching Neurons from EM Data
Funke J. Andres B. Hamprecht F. Cardona A. and Cook M. (2012), Efficient Automatic 3D-Reconstruction of Branching Neurons from EM Data, in Computer Vision and Pattern Recognition, Piscataway, New Jersey, USInstitute of Electrical and Electronics Engineers, New Jersey, US.
Elastic volume reconstruction from series of ultra-thin microscopy sections
Saalfeld S. Fetter R. Cardona A. and Tomancak P. (2012), Elastic volume reconstruction from series of ultra-thin microscopy sections, in Nature Methods, 9, 717-720.
Robust Non-Rigid Registration of 2D and 3D Graphs
E. Serradell F. Moreno J. Kybic and P. Fua (2012), Robust Non-Rigid Registration of 2D and 3D Graphs, in Computer Vision and Pattern Recognition, Providence, RI, USAInstitute of Electrical and Electronics Engineers, New Jersey, US.
Altered synaptic dynamics during normal brain aging
Mostany R Anstey JE Crump KL Maco B Knott G and Portera-Cailliau C, Altered synaptic dynamics during normal brain aging, in Journal of Neuroscience.
Correlative in vivo 2 Photon and Focused Ion Beam Scanning Electron Microscopy of Cortical Neurons
Maco B Holtmaat A Cantoni M Kreshuk A Straehle CN Hamprecht F Knott GW, Correlative in vivo 2 Photon and Focused Ion Beam Scanning Electron Microscopy of Cortical Neurons, in PLoSONE.
Diversity of thalamorecipient spine morphology in cat visual cortex and its implication for synaptic plasticity
N. M. Costa, Diversity of thalamorecipient spine morphology in cat visual cortex and its implication for synaptic plasticity, in Journal of Comparative Neurology, 2058-2066.
Functional development of the olfactory system in zebrafish
Miyasaka N Wanner AA Li J Mack-Bucher J Genoud C Yoshihara Y Friedrich RW, Functional development of the olfactory system in zebrafish, in Mech Dev.
SuperSlicing frame restoration for anisotropic ssTEM
Laptev Dmitry, Vezhnevets Alexander, Buhmann Joachim, SuperSlicing frame restoration for anisotropic ssTEM, in IEEE 11th International Symposium on Biomedical Imaging ISBI 2014, BeijingMicrotome Publishing, -.

Collaboration

Group / person Country
Types of collaboration
Massachusetts Institute of Technology (MIT) United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Society for Neuroscience 2016 Poster Automated dense collection of ultrathin sections directly onto silicon wafers 12.11.2016 San Diego, United States of America Hahnloser Richard; Templier Thomas;
Pattern Theory Lunch Seminar Series Individual talk Big data in neuroscience: Where is the information? 04.12.2013 Brown University, Providence, United States of America Buhmann Joachim;
Society for Neuroscience 2013 Poster A correlative light and electron microscopy approach for reconstructing syringeal motor neuron circuits in a songbird 07.11.2013 San Diego, United States of America Hahnloser Richard; Templier Thomas;
Fall 2013 GRASP Seminar Individual talk Big Data: Where is the information? 27.09.2013 GRASP Lab, University of Pennsylvania, United States of America Buhmann Joachim;
ZNZ Symposium 2013 Poster Quantifying the local circuit of macaque cortex. 13.09.2013 Zurich, Switzerland Martin Kevan;
Informatik-Kolloquium Individual talk Big Data: where is the information 13.08.2013 TU Braunschweig, Germany Buhmann Joachim;
HHMI Janelia workshop Talk given at a conference Pattern classification in the olfactory system 09.06.2013 Ashburn, VA, United States of America Friedrich Rainer;
IbPRIA 2013 Talk given at a conference Big Data: Where is the information? 05.06.2013 Madeira, Portugal Buhmann Joachim;
Sinergia 2013 Talk given at a conference EM reconstructions of synaptic targets of Layer2/3 pyramidal neurons in cat visual cortex 25.05.2013 Zurich, Switzerland Martin Kevan;
Giessbach Meeting Talk given at a conference Reconstruction of neuronal activity and connectivity patterns in the zebrafish olfactory bulb 23.05.2013 Giessbach, Switzerland Wanner Adrian;
25th Aniversary of the IWR, Heidelberg Talk given at a conference Big data: where is the information? 21.02.2013 Universiät Heidelberg, Germany Buhmann Joachim;
Songbird European meeting 2013 Poster A correlative light and electron microscopy sample preparation for large scale mapping of neuronal connectivity 04.02.2013 Odensee, Denmark Hahnloser Richard; Templier Thomas;
Swiss Society for Neuroscience (SSN) Annual Meeting 2013 Poster Auditory versus motor cortex, a structurual comparison in the mouse 02.02.2013 Geneva, Switzerland Martin Kevan;
Swiss Society of Neuroscience 2013 Poster A correlative light and electron microscopy sample preparation for large scale mapping of neuronal connectivity 02.02.2013 Geneva, Switzerland Hahnloser Richard; Templier Thomas;
Neuroscience 2012 Poster Reconstruction of neuronal activity and connectivity patterns in the zebrafish olfactory 13.10.2012 New Orleans, United States of America Wanner Adrian; Friedrich Rainer;
MICCAI Poster TBD 01.10.2012 Nice, France, France Hahnloser Richard;
Computer Vision and Pattern Recognition (CVPR) 2012 Poster TBA 16.06.2012 Providence, RI, USA, United States of America Funke Jan;
NCCR Neuro Concluding Symposium 2012 Poster Who's who in the cortical neuropil? An immuno ultrastructural studyof macaque area V1. 14.06.2012 Zurich, Switzerland Martin Kevan;
Neuronal Circuits 2012 Poster A quantitative comparision between the visual cortex of the cat and the auditory cortex of the mouse 28.03.2012 Cold Spring Harbor, United States of America Martin Kevan;
Primate Neurobiology Meeting 2012 Poster Who's who in the cortical neuropil? An immuno ultrastructural studyof macaque area V1. 12.03.2012 Tuebingen, Germany Martin Kevan;
Microscopy conference Talk given at a conference Reconstruction of neuronal activity and connectivity patterns in the zebrafish olfactory bulb. Invited talk at “International symposium on 3D microscopy 09.03.2012 Les Diablerets, Switzerland Wanner Adrian;
Swiss Society of Optics and Microscopy 3D-Symposium 2012 Talk given at a conference The thalamocortical pathway artistically considered 05.03.2012 Les Diablerets, Switzerland, Switzerland Martin Kevan;
Meeting of Swiss Society for Neuroscience 2012 Poster How many synapses does a mouse auditory cortical neuron form? 03.02.2012 Zürich, Switzerland, Switzerland Martin Kevan;
ZNZ Symposium 2011 Poster The diversity of thalamorecipient spine morphology in cat visual cortex and its implication for synaptic plasticity 16.09.2011 Zurich, Switzerland, Switzerland Martin Kevan;
Janelia Farm/HHMI Meeting on “High resolution circuit reconstruction” Talk given at a conference TrakEM2 and CATMAID software for neural circuit reconstruction from serial section EM 11.09.2011 Ashburn, VA, USA, United States of America Cardona Albert; Funke Jan;
Janelia Meeting Circuit Reconstruction Talk given at a conference Analysis of activity and connectivity patterns in the zebrafish olfactory system 09.09.2011 Ashburn, VA, United States of America Friedrich Rainer;
Janelia Meeting Circuit Reconstruction Poster High-resolution analysis of synaptic connectivity in the olfactory bulb of zebrafish larvae 09.09.2011 Ashburn, VA, United States of America Friedrich Rainer; Wanner Adrian;
Janelia Meeting Circuit Reconstruction Poster Reconstruction of neuronal activity and connectivity patterns in the zebrafish olfactory bulb 09.09.2011 Ashburn, VA, United States of America Friedrich Rainer; Wanner Adrian;
Portuguese Society for Neuroscience 2011 Poster The diversity of thalamorecipient spine morphology in cat visual cortex and its implication for synaptic plasticity 25.05.2011 Lisbon, Portugal Martin Kevan;
Swiss Society for Neuroscience meeting 2011 Poster The diversity of thalamorecipient spine morphology in cat visual cortex and its implication for synaptic plasticity 26.03.2011 Basel, Switzerland, Switzerland Martin Kevan;


Self-organised

Title Date Place
Neural Skircuit Reconstruction Meeting 01.03.2014 Andermatt, Switzerland
Sinergia Meeting 2011 12.04.2011 Zurich, Switzerland

Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Big Data in Medicine: where is the valuable information for patients? German-speaking Switzerland 2013

Associated projects

Number Title Start Funding scheme
172925 Bottom-up and top-down neuronal computations in olfaction 01.04.2018 Project funding
160663 Songbirds as model for speech acquisition in humans 01.03.2015 International short research visits
133846 Focused Ion Beam Scanning Electron Microscope (FIBSEM) 01.11.2011 R'EQUIP
149866 Delineating Trees in Noisy 2D Images and 3D Image-Stacks 01.10.2013 Project funding

Abstract

The history of natural sciences has taught us that a new discipline emerges whenever the length scale of investigation is reduced by about three orders of magnitude. The recent development of 3-D electron microscopy (3DEM) techniques induces such a transition by allowing the ultrastructural analysis of biological tissues throughout large volumes (up to a few hundred micrometers in each dimension). Although 3DEM has an enormous potential for advancing our understanding of brain function in health and disease, its biomedical application is currently impeded by the lack of accessory technologies, particularly informatics tools for the automated analysis of large and complex sets of image data. The scope of our Sinergia Proposal is to develop technologies for using 3DEM and reconstruct neuronal circuits in the vertebrate brain.High-throughput 3DEM hardware for large-scale brain imaging is currently developed at a rapid pace. However, there are many experimental hurdles in the way of achieving a synaptic resolution level of analysis of dense neuropil. Most importantly, the tools to extract relevant information from the large and extremely complex image stacks are virtually non-existent. Today, the only available method for 3DEM image processing is manual image segmentation. However, methods with strong reliance on human input are not feasible for the analysis of large tissue volumes. Our goal is therefore to develop automated analysis procedures for 3DEM data based on computer vision approaches. We propose to develop state-of-the-art 3DEM technologies, in which we integrate lower-resolution light microscopy (LM) and multicolor staining techniques. Our technological goal is to design a workflow for the acquisition of high-quality 3D image stacks of brain tissue and to develop computational methods for the automated extraction of all connectivity information contained in 3DEM image stacks. In particular, we will design computational tools for the registration of EM and LM imagery, for annotating features in EM data to identify synapses and other subcellular structures, for classifying image voxels to aid volumetric image segmentation, and for tracing of neuron morphologies based on local and global information. We will apply 3DEM techniques to determine connectivity patterns in three vertebrate model circuits: the olfactory system of zebrafish, the song control system of zebra finches, and the neocortex. Since each of these systems is also intensively studied at the physiological level, the connectivity information we provide through our efforts can be used directly to construct quantitative circuit models and derive structural principles governing circuit function. Our project is interdisciplinary and we are composed of neurobiologists and computer vision scientists. We are divided into groups that work on different animal models and pursue different 3DEM approaches. The groups will benefit from each other’s work on virtually all levels because we develop methods that are compatible among the groups and applicable to essentially all animal species. We anticipate that our methods and developments for ultrastructural imaging and analysis will contribute significantly to a new field of research (sometimes referred to as ‘connectomics’ or ‘projectomics’) and make critical progress towards one of the major goals in systems neurobiology, which is the explanation of how brain circuits function.
-