Journal: bioRxiv
Article Title: Directionality bias is necessary to explain spatiotemporal progression of pathology in mouse models of tauopathy
doi: 10.1101/2024.06.04.597478
Figure Lengend Snippet: A. & B. Schematics showing the etiology of directional spread bias at the microscopic and network levels. Inside of axons, pathological tau can migrate by passive diffusion or through energy-dependent directed transport either in the anterograde (parallel to axon polarity) or retrograde (antiparallel to axon polarity) directions ( A ). At a network level, this manifests as an directionally biased flow along the directed connectome B. By convention, c ij indicates a connection originating in region i and terminating in region j , therefore a net flow from i to j along c ij would be considered to be anterograde-biased . C. The Allen Mouse Brain Connectome Atlas (AMBCA) ) visualized as a heatmap. D. Scatterplots showing the associations between the regional end-timepoint (9 MPI) pathology in the IbaStrInj ) experiment (see ) and the average connectivity from ( left ) and ( right ) seeded regions CP and MOp. Tau shows a highly significant association with incoming but not outgoing connectivity. E. Violin plots showing the associations between tau pathology across all studies and time points and three pairs of region-level graph metrics; from right to left: outgoing and incoming connectivity to seed, out- and in-degree, and the first eigenvectors ( v 1 ) of L ret and L ant (see Materials and Methods ). One-sample t-statistics were calculated for each metric and two-sample t-statistics were calculated for each metric pair. All t-statistics were highly significant. F. Glass brain visualizations of end-timepoint IbaStrInj pathology and connectivity from ( top ) and to ( bottom ) seed regions (orange spheres). The low association between outgoing seed connectivity is in part driven by strong contralateral telencephalic and ipsilateral hindbrain projections (red boxes), which do not exhibit significant tau pathology. By contrast, the seeded regions predominantly receive connectivity from ipsilateral forebrain regions, which do exhibit pronounced tau pathology (blue box). MPI – months post injection; CP – caudoputamen; MOp – primary motor cortex. * – p < 0.05; ** – p < 0.01; *** – p < 0.001.
Article Snippet: Exploring directionality requires the use of a directed connectome, which has been previously determined using viral tracing methods in wild-type mice by the Allen Institute for Brain Science (AIBS) ); here, we use a 426-region, bilateral version of the Allen Mouse Brain Connectome Atlas (AMBCA) ( ).
Techniques: Diffusion-based Assay, Injection