Project

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Reconstruction and analysis of neural circuits in the Drosophila larval nerve cord

English title Reconstruction and analysis of neural circuits in the Drosophila larval nerve cord
Applicant Cardona Albert
Number 132969
Funding scheme Project funding
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 01.07.2011 - 31.05.2013
Approved amount 201'681.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Information Technology

Keywords (9)

neuroscience; neuronal reconstruction; wiring diagram; microcircuitry; somatosensory processing; serial section electron microscopy; neuronal modeling; behavioral testing; Drosophila

Lay Summary (English)

Lead
Lay summary
To understand brain function and development we must examine its structure. In the nervous system, the precise wiring diagram of all neurons-their arborizations and their synapses-determines its information processing and storage capabilities. By choosing a model organism of suitable dimensions, we have the opportunity to reconstruct complete functional units of the nervous system.The ventral nerve cord of the fruit fly (Drosophila) larva contains central pattern generating circuits that underlie locomotion, and receives afferent axons from the body wall somatosensory neurons. Numerous studies have identified key genetic, developmental and structural similarities of the insect nerve cord with the vertebrate spinal cord. With less than 6000 neurons, the ventral nerve cord of the fruit fly larva is an excellent model system in which to study somatosensory information processing (from pain, touch, sound/vibration and muscle stretch) and motor control.The arbors of all sensory neurons that project into a segment of the nerve cord, and of its motorneurons, have been characterized with light microscopy. The arborizations of interneurons are currently being described by Dr. Jim Truman, our collaborator at HHMI Janelia Farm, using GFP reporter constructs and a novel library of single neural-class specific GAL4 driver lines (Pfeiffer et al, 2008). However, these light-level descriptions only provide putative connectivity diagrams, based on overlap of axonal and dendritic arbors.We propose to use serial section transmission electron microscopy (ssTEM), to fully reconstruct one segment of the nerve cord of a newly hatched first instar larva. We have already obtained a serial section set, which we already have automatically imaged and registered into an analyzable image volume. We will reconstruct all neuronal arbors, and identify and classify all synapses, with custom-designed software TrakEM2 that we have developed in the past 5 years. Our reconstructions will yield the wiring diagram of a complete segment. The project will yield neuroanatomical and circuit detail of the larval VNC at an unprecedented resolution, which is indispensable for understanding sensory information processing and circuit assembly.The identification of connectivity patterns between all the neuron classes in the VNC will open the doors for studying the coordinate assembly of entire circuits, rather than isolated individual members of a circuit. A detailed synaptic level description of the VNC circuitry will provide important insights into the mechanisms that underlie somatosensory processing, and the generation of locomotor patterns by the central pattern generator circuitry.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
TrakEM2 Software for Neural Circuit Reconstruction
Cardona A, Saalfeld S, Schindelin J, Arganda-Carreras I, Preibisch S, Longair M, Tomancak P, Hartenstein V, Douglas RJ (2012), TrakEM2 Software for Neural Circuit Reconstruction, in PLOS ONE, 7(6), e38011-e38011.

Collaboration

Group / person Country
Types of collaboration
IDSIA Switzerland (Europe)
- 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
Seminar, Reconstructing neural circuits from electron microscopy image volumes 19.07.2012 Institute of Robotics, Barcelona, Spain
Seminar, Neurobiology of Drosophila larva 16.07.2012 Centre for Genomic Regulation, Barcelona, Spain
High Resolution Neural Circuit Reconstruction meeting 11.09.2011 HHMI Janelia Farm, Ashburn, VA, USA


Self-organised

Title Date Place
CATMAID software development sprint 05.07.2011 HHMI Janelia Farm, Ashburn, VA, USA

Awards

Title Year
Fellow (lab head) at HHMI Janelia Farm, equivalent to Assistant Professor (3 million for 5 years) 2011

Abstract

To understand brain function and development we must examine its structure. In the nervous system, the precise wiring diagram of all neurons-their arborizations and their synapses-determines its information processing and storage capabilities. By choosing a model organism of suitable dimensions, we have the opportunity to reconstruct complete functional units of the nervous system. The ventral nerve cord (VNC) of Drosophila larva contains central pattern generating circuits (CPGs) that underlie locomotion, and receives afferent axons from the body wall somatosensory neurons. With a reduced number of neurons, the VNC is an excellent model system in which to study somatosensory information processing and motor control. Over many decades, studies of the development of the Drosophila embryonic VNC have provided key insights into the mechanisms underlying neuron type specification and differentiation, axon guidance and termination of sensory and motor neurons. The arbors of all sensory neurons that project into a VNC segment, and of its motorneurons, have been characterized with light microscopy. The arborizations of VNC interneurons are currently being described by Dr. Jim Truman, our collaborator, using GFP reporter constructs and a novel library of single neural-class specific driver lines (Pfeiffer et al., 2008). However, these light-level descriptions only provide putative connectivity diagrams, based on overlap of axonal and dendritic arbors. We propose to use serial section transmission electron microscopy (ssTEM), to fully reconstruct one segment of the VNC of a newly hatched first instar larva of Drosophila. We have already obtained a serial section set, which we already have automatically imaged and registered into an analyzable image volume. We will reconstruct all neuronal arbors, and identify and classify all synapses, with custom-designed software that we have developed in the past 5 years. Our reconstructions will yield the wiring diagram of a complete VNC segment. We will analyze the spatial distribution of synapses and overall circuitry organization. In collaboration, we will model and test neural circuit function with targeted genetic disruption of neural function and behavioral assays of freely behaving larvae. The project will yield neuroanatomical and circuit detail of the larval VNC at an unprecedented resolution, which is indispensable for understanding sensory information processing and circuit assembly. The identification of connectivity patterns between all the neuron classes in the VNC will open the doors for studying the coordinate assembly of entire circuits, rather than isolated individual members of a circuit. A detailed synaptic level description of the VNC circuitry will provide important insights into the mechanisms that underlie somatosensory processing, and the generation of locomotor patterns by the central pattern generator circuitry.
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