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Junior Research Group: Computational Neuroanatomy

The network reconstruction pipeline. a) Boundary surfaces defining cell type locations. b) Soma distribution inside one column. c) Cell type assignment. d) Dendrite reconstructions, coloured by cell type. e) Thalamocortical axon reconstructions

A cortical column is thought to represent the elementary functional unit of the mammalian cortex. In rodent vibrissal cortex, an anatomical equivalent, designated as a “barrel column”, has been described. The well-defined anatomical layout and the one-to-one correspondence between a single facial whisker and a barrel column render the vibrissal system as the ideal starting point to reverse engineer the structure and function of neural microcircuits. My research focuses on developing imaging, image processing and analysis tools that allow (i) obtaining the 3D anatomical data that is necessary to reconstruct neural circuits, (ii) assembling average, anatomically realistic neural networks and (iii) simulating signal flow within the resulting large-scale, full-compartmental models of thousands of neurons and millions of synaptic contacts.

First, we developed a semi-automated imaging and tracing pipeline, called NeuroMorph, which allows reconstructing the complete 3D dendrite and axon morphology of individual neurons, labelled in vivo [6,8,10,11,14]. Compared to state-of-the-art manual tracing tools it reduces the reconstruction time from several months to approximately three days. More importantly, the results are independent of the experience and performance of a human tracer. Using NeuroMorph, we reconstructed morphologies from all excitatory cell types in rat vibrissal cortex and thalamus [1,2,5]. Second, we developed an image processing pipeline, called NeuroCount, which allows automated detecting of neuron somata within large brain volumes [4,9]. Using NeuroCount, we determined the number and 3D distribution of all neurons within rat vibrissal cortex and thalamus [7]. Third, we developed an interactive, visual-computing tool, called NeuroNet, which allows assembling average 3D network models that are based on anatomical data obtained by NeuroMorph and NeuroCount [3,12]. NeuroNet allowed reconstructing the cell type-specific excitatory network of a rat barrel column and estimating synaptic innervation of each excitatory neuron by the thalamus [2]. Finally, we developed a concept to investigate signal flow within average network models using Monte Carlo simulations. The resultant simulation framework, called NeuroDUNE, was designed and implemented by Dr. Stefan Lang as part of a Bernstein collaboration with the University of Heidelberg. Using NeuroDUNE, we simulated the activation of an excitatory network in a barrel column by thalamocortical input after whisker deflection [3]. In summary, the described concepts and tools open the possibility to (i) reconstruct the average 3D structure and synaptic wiring of large brain structures, (ii) simulate signal flow within anatomically realistic network models, (iii) compare simulations with functional imaging data and (iv) elucidate mechanistic principles underlying sensory-evoked signal flow.

First, based on the column model described above, we are generating anatomically realistic models of identified thalamocortical and intracortical microcircuits [15] and simulate their function during whisker-evoked excitation. Particular emphasis is placed on the effects of synchronous inputs to different cell types and during different stimulus conditions. Second, we are extending the model of one cortical column to an anatomically realistic model of the complete vibrissal sensory and motor pathways. In particular, we reconstruct all axons projecting out of a cortical column. Finally, we are developing an automated imaging and reconstruction method to determine functional and anatomical connectivity between pairs of neurons labelled in vivo. This involves establishing a high-speed confocal imaging system to trace axon morphologies throughout large brain areas.

Project leader: Marcel Oberlaender
Coworkers: Simon Broghammer*, Robert Egger*, Rajeev Narajanan, David Slabik*, Christopher Tull*, Max Wolf*
*funded by BMBF

Key publications:

  • Oberlaender M, Boudewijns ZSRM, Kleele T, Mansvelder HD, Sakmann B & de Kock CPJ; Three-dimensional axon morphologies of individual layer 5 neurons indicate cell type-specific intracortical pathways for whisker motion and touch. Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4188-93
  • Oberlaender M, Ramirez A & Bruno RM; Sensory experience restructures thalamocortical axons during adulthood. Neuron. 2012 May 24;74(4):648-55.
  • Oberlaender M, de Kock CPJ, Bruno RM, Ramirez A, Meyer HS, Dercksen VJ, Helmstaedter M & Sakmann B; Cell Type-Specific Three-Dimensional Structure of Thalamocortical Circuits in a Column of Rat Vibrissal Cortex. Cereb Cortex. 2011 Nov 16. [Epub ahead of print].

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