Project leads: Nuno da Costa, Forrest Collman & Clay Reid

Team members: Agnes Bodor,  Derrick Brittain,  Steven Cook, Bethanny Danskin, Cameron Devine, Chris Jordan, Cheryl Lea, Melissa Lerch, Xiaoyu Lu, Sid Rath, Ben Pedigo, Jenna Schardt, Casey Schneider-Mizell, Rachael Swanstrom, Marc Takeno, Russel Torres, Keith Wiley, Wan-qing Yu, Chi Zhang, Kim Gruver

Electron Microscopy Connectomics

In order to reconstruct neural circuits at a large scale with synaptic resolution, electron microscopy offers unique advantages in capturing the detailed morphology of all individual neurons and non-neuronal cells within a volume.  By applying high throughput sectioning, imaging, image processing, and automated segmentation, our team contributes to large-scale reconstructions of neural circuits.  We have published work primarily on the reconstruction of visual circuits of the mouse, but have future looking projects moving toward reconstructions of motor circuits in mouse and monkey, and basal ganglia circuits of the mouse. We are also leading one of the centers of the larger NIH BRAIN CONNECTS effort to scale up pipelines to capture the synaptic connectivity of the entire whole mouse. Our team consists of an interdisciplinary group that combines expertise in electron microscopy,  neuroscience, computer science, mechanical engineering and program management to execute this complex pipeline.

Axonal Connectomics

While the EM connectomics has formed the bulk of our research over the past decade, 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 year, the required data sizes make it impossible to do EM imaging of entire human brain. With lower resolution, however, it is an achievable goal to map the majority of large (myelinated) axons in the coming years. Given that never has a single axon been traced from source to target through the human white matter, a new approach is clearly needed.

With a combination of antibody staining, tissue clearing, expansion, and light-sheet microscopy, we have begun mapping the courses of projection axons in large brains at high resolution. 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 larger brains, including the human.

Project Lead: Clay Reid

Team Members: Soumya Chatterjee, Steven Cook, Ayana Hellevik, Cheryl Lea, Kevin Takasaki, Russel Torres, Emily Turschak, Kareena Villalobos, Wan-Qing Yu

Non-departmental members: Olga Gliko, Uygar Sumbul