Tracing Neuronal Circuits 2: The Mesoscale Connectome

    23/04/2014

    This new article in Nature came out recently and I found it fascinating, since they use a similar technology to us.

    Mesoscale

    Hongkui Zeng and colleagues have used AAV-EGFP to trace the entire mesoscale architecture of the mouse cortex. Macroscale regions of the brain represent volumes greater than 1 mm cubed. Microscale connectivity represent regions smaller than 1 mm cube, visualized by the electron microscope. Mesoscale connectivity aims to describe large and small regions of connectivity, bridging the differences between the Macro and microscale. This paper is the first instance that anyone has used AAV-EGFP viral tracers to analyze the mesoscale connectome of the adult mouse brain for the Allen Mouse Brain Connectivity Atlas.

    The authors used AAV-2 with a synapsin I promoter (mostly neuron specific). They collected 469 images after injecting various sites that covered the whole brain (I feel sorry for the person who had to do the endless number of injections!?). In total they mapped 295 brain structures to their connections. They promise this is only Phase I of II. In Phase II they will use a Cre dependent AAV vector, presumably to map the secondary order projections.

    Interestingly they use systems computational methods such as graph theory, cluster analysis and network motifs to provide quantitative connectivity data for the vertebrate brain, which hitherto has only been done in C. elegans. Here are some cool images they published:

     

    tractography3D tractography paths, tracing the topographical projections between the cortex, striatum and thalamus. Two hemispheres of the cortex shown in (d). Ipsilateral caudoputamen shown in (e). Top-down view of the ipsilateral thalamus shown in (f).

     

    brainCortical neurons are labeled with AAV-EGFP (Green) and conventional BDA tracer (Red) and DAPI counterstain (Blue). AAV and BDA was injected into the same site at the motor cortex (Yellow, MOp). Confocal imaging shows uptake of the BDA tracer overlaps with the AAV (b, b' and b'').

     

    cortexCortical projections in the contralateral primary motor cortex (c), ipsilateral primary somatosensory cortex (d), agranular insular area (e) and prirhinal cortex (f) labeled with the same tracers mentioned above.