Abstract: Connectomics is a strategy for mapping complex neural networks based on high-speed automated electron optical imaging, computational assembly of neural data volumes, web-based navigational tools to explore terabyte to petabyte image volumes, and annotation and markup tools to convert images into rich networks with cellular metadata. These collections of network data and associated metadata, analyzed using tools from graph theory and classification theory, can be merged with classical systems theory, giving a more completely parameterized view of how biologic information processing systems are implemented in retina and brain. Networks have two separable features: topology and connection attributes. 

The first findings from connectomics strongly validate the idea that the topologies of complete retinal networks are far more complex than the simple schematics that emerged from classical anatomy. We also know that challenges to vision loss from age-related macular degeneration (AMD), retinitis pigmentosa (RP) alter network topologies. These alterations impact international efforts to develop late-stage vision restoring therapies including cell / tissue implants, optogenetics, photoswitches, and prosthetic implants, all requiring survival of the neural retina. It has often been asserted that the surviving neural retina is essentially unchanged in RP, but that is false. Remodeling includes neuronal death, rewiring, ectopic synapse formation, cell migration and emigration, glial transformations, and even vascular remodeling. Most of our knowledge of remodeling is based on analyses of short lifespan rodents using experimental tools that, with exceptions, are impossible with human autopsy tissue. 

We are applying the same connectomics strategies to disease tissues, creating patho-connectomes. These pathoconnectomes and other work demonstrates that retinal degenerations are binary diseases: acute photoreceptor degenerations convert to chronic neurodegenerations similar to progressive brain diseases. Targeting specific defects will be critical to achieving rescues vision rescue by molecular, cellular, or engineering approaches. We will demonstrate retinal plasticity from early to late stage, reveal networks affected, and discuss circuit topologies involved with metabolic chaos and collapse, the nature and scope of rewiring and neuronal loss.

Host: Marcel Bruchez, Ph.D.