Project: Long Range Connectivity Reconstruction


 

Long Range Connectivity Reconstruction

Award:

ARRA 1RC1NS069152


 

Long range connectivity studies of brain histology.

 

New technologies for neuroscience research

Establishing a network diagram of the brain is one of the major challenges of modern neurobiology and medicine. Nowhere is this clearer than for the social-emotional system, where dysregulation of circuitry has been implicated in depression, schizophrenia, and autism. Although we now have the technology to begin to understand the connectivity among closely-spaced neurons and distant large structures, we are unable to follow or visualize long-range projections of critical systems at the axon or tract level. The Scientific Computing and Imaging Institute at the University of Utah has recently published a landmark paper: The Generation of a Computational Framework for Ultrastructural Mapping of Neural Circuitry. Their methods have enabled large-scale connectivity analyses at the ultrastructural level and generated terabyte-scale image volumes that previously would require decades of assembly but that now can be completed in months. The next step for these ultrastructural computational tools is the possibility to provide powerful solutions for the problem of brain connectivity beyond the mm scale, to the scale of many centimeters. At UCNIA, we are taking that step and developing the next generation of neurobiological technologies and novel software tools needed for three-dimensional reconstructions from serial sections of long-range axon projections.

It is our ultimate goal to generate the computational tools for combining genetic, neuroanatomic, and image-reconstructive technologies to create genetically coded, three dimensional maps of axon projections from the hypothalamus to a subset of targets in the limbic system. We are utilizing serial sections of brains in the size range of primates, and are beginning to integrate genetic projection maps with high resolution in-vivo and ex- vivo neural imaging (DTI and MRI).

 

Registration of Neuron Confocal Microscopy

Active research in the area of 3-D neurite tracing has predominantly focused on single sections. Ultimately, however, neurobiologists desire to study the long-range connectivity of the brain, which requires tracing axons across multiple serially-cut sections. Registration of axonal sections is challenging due to several factors, such as sparseness of the axons and complications of the sectioning process, including tissue deformation and loss. We’ve also investigated a method for registering sections using centerline traces that provide the locations of axons at section boundaries and the angles at which the axons approach the boundaries. This information is used to determine correspondences between two serial sections. Both global and local differences are accounted for using rigid and non-rigid transforms. Results show that utilizing information from traced axons allows axon continuity across sections to be restored.

 

 

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