Experimental Quality Control Induces Changes in Allen Mouse Brain Connectomes

Authors

Nathan, V., Tullo, S., Herrera-Portillo, L., Devenyi, G., Yee, Y., Chakravarty, M. M.

Abstract

The Allen Mouse Brain Connectivity Atlas (AMBCA) is widely used to represent structural connectivity in the mouse brain. The AMBCA consists of tracer injection experiments where neuronal projections axonally connected to the initial injection site are labelled. The resulting whole-brain structural connectomes, derived from a subset of these experiments in C57BL/6 mice, have been used in several studies of connectomic architectures. However, through close inspection of n=437 distinct experiments used in a publicly-available connectome (Knox et al., 2018), we observed experiments with off-target injections, diffuse projections, unrealistically small injections and projections, and anatomical misalignments, affecting the accuracy and applicability of these connectivity experiments. We applied a combined automated and manual quality control (QC) and identified n=56 (~13% of the original n=437) experiments representing a wide variety of injection and projection failures across the brain. Automated QC was used to detect extreme injection and projection sizes and misalignments, while manual QC was used to detect subtle off-target tracer spreading. Using the remaining n=375 experiments, we rebuilt two different connectomes using previously-published methods; specifically: the regionalized voxel model from Knox et al. (2018), and the homogeneous model from Oh et al. (2014). Our rebuilt connectomes show strong losses in connectivity between regions with limited evidence of structural connectivity by other methods (e.g. hippocampus-medulla, cerebellum-isocortex) and gains in connectivity between regions with strong connectivity evidence (hypothalamus-cerebellum, hypothalamus-isocortex). Finally, we analyzed the rich club and community organization to demonstrate the potential downstream impacts on the representation of the overall structural connectome architectures of our QC'd connectomes and observed subtle whole-brain organizational changes. We present our rebuilt connectomes, and particularly highlight the regionalized voxel model, as more accurate representations of structural connectivity derived from the AMBCA.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 24 Feb 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.