4.8 Article

Mapping remodeling of thalamocortical projections in the living reeler mouse brain by diffusion tractography

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1218330110

Keywords

fiber tracking validation; brain developmental plasticity

Funding

  1. Deutsche Forschungsgemeinschaft [SFB780 TP C1]
  2. BrainLinks - BrainTools Freiburg Cluster of Excellence (MouseNet) [P31]
  3. Center of Molecular Physiology of the Brain, Gottingen [B1]
  4. Humboldt Foundation

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A major challenge in neuroscience is to accurately decipher in vivo the entire brain circuitry (connectome) at a microscopic level. Currently, the only methodology providing a global noninvasive window into structural brain connectivity is diffusion tractography. The extent to which the reconstructed pathways reflect realistic neuronal networks depends, however, on data acquisition and postprocessing factors. Through a unique combination of approaches, we designed and evaluated herein a framework for reliable fiber tracking and mapping of the living mouse brain connectome. One important wiring scheme, connecting gray matter regions and passing fiber-crossing areas, was closely examined: the lemniscal thalamocortical (TC) pathway. We quantitatively validated the TC projections inferred from in vivo tractography with correlative histological axonal tracing in the same wild-type and reeler mutant mice. We demonstrated noninvasively that changes in patterning of the cortical sheet, such as highly disorganized cortical lamination in reeler, led to spectacular compensatory remodeling of the TC pathway.

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