Building on these contributions, Dong’s proposed “Integrative Connectome” may be his most ambitious project yet. “It’s very important to look at neural circuitry globally, but also at cellular resolution,” said Dong. “We use different technologies to compare across animal models so we can get a comprehensive and integrative view of the entire neural circuitry.” While Dong’s previous work has employed manual tracing, viral tracing, and gene expression methods, his new Integrative Connectome will incorporate even more data modalities. This will require the use of highly advanced technologies to collect, integrate, and analyze data spanning anatomy, physiology, molecular genetics, behavior, and functional imaging. Dong envisions that this novel connectome resource will provide a “Google Map of the brain,” allowing users to toggle and overlay different views of the brain, just as Google Maps displays topography, street view, and satellite images, all within a standardized frame. Researchers will zoom in to examine specific structures, and zoom out to visualize the brain’s global wiring. The ultimate goal is to provide an intuitive way to compare data from individual studies against a standardized reference.

Identifying the Brain’s Neuronal Cell Types

While neuroscientists have made significant progress toward understanding the structure and function of the brain, identifying classes of neuronal cell types has remained a challenge—one which the CIC plans to undertake. “Each of these anatomically-defined brain regions contains many different cell types that are positioned next to each other. Their connectivity may be different; their gene expression is different; their function is different,” Dong said. A single data modality, be it gene expression, neuromorphology, or connectivity, is not enough to accurately classify a cell type. Only by simultaneously examining all of these diverse properties will we develop a robust understanding of how each type of neuron works individually, and what contribution it makes to the broader network.

Classifying neuronal cell types is not simply a matter of anatomical precision; it has critical implications for understanding and treating neurological diseases. Identifying the properties of different cell types will help scientists develop tools to selectively manipulate them, and open doors for new targeted therapeutics with minimal side effects.

With this in mind, the CIC has moved beyond mapping healthy brains to investigate the neural circuitry underlying diseases such as Huntington’s Disease and autism.

“Our connectome will build bridges for all these knowledge gaps,” said Dong. “We build the normal connectome in order to understand how this connectivity is disrupted. Then we can begin to address different neuropsychiatric diseases.”