Johns Hopkins School of Medicine

Axonal Connectomics of the Human Brain

Our group studies detailed wiring diagrams of the brain, or connectomics. While EM connectomics has formed the bulk of our research over the past two decades, the newer Axonal Connectomics project aims to apply connectomics approaches to larger brains, with the complete human brain as the ultimate goal. While the EM approach can reasonably be applied to the entire mouse brain in the coming years, the required data sizes make it impossible to do EM imaging of the entire human brain. With lower resolution, however, it is an achievable goal to map the majority of large (myelinated) axons. Because no single axon has ever been traced from source to target through the human brain, a new approach was clearly needed.

Our work on the connectomics of the human brain employs a combination of antibody staining of axons, tissue clearing, expansion, and light-sheet microscopy. The resultant three-dimensional data sets are readily segmented both by humans and with machine-learning approaches, similar to those used with electron microscopy. We are currently working to scale up our centimeter-scale data sets to increasingly large portions of the human brain.

In a related project, we are using super-expansion (20X) and pan-protein staining, which achieves data sets comparable to serial-section EM, with the goal of creating a nanoscale atlas of the mouse brain. 

This work builds on our earlier research in electron microscopy connectomics. Beginning in 2006 at Harvard, we carried out the first connectomics study of the cerebral cortex combined with calcium imaging of visual responses (Bock et al., 2011; Lee et al., 2016). At the Allen Institute, we participated in the IARPA MICrONS program, imaging a cubic mm of visual cortex and analyzing synaptic circuits in the context of physiological recordings (microns-explorer.org)