The brain remains critically understudied. How are brains so much more powerful and more energy efficient than any in silico system? What is the cause of brain circuit disorders such as schizophrenia or autism? How dynamic are brain circuits? To answer these and many other questions — or even to formulate testable hypotheses about them — we need more and better maps of the brain.

Brain mapping at synaptic resolution — often referred to as “connectomics” — has traditionally relied on electron microscopy to construct nanoscale “wiring diagrams” from neuronal morphology. A new paradigm is now emerging: “molecular connectomics.” In molecular connectomics, we combine morphological “wiring diagrams” with multimodal readouts of molecular information, from proteins to RNA and activity, and beyond. This is made possible by expansion microscopy, which allows access to the full molecular biology toolbox paired with speedy super-resolution imaging on conventional light microscopes.

You will utilize these new paradigms and tools to understand the hardware of biological computation at the molecular level. You will generate maps of large and diverse brain circuits at unprecedented molecular detail, and use these maps to formulate and test new hypotheses for many open questions in neuroscience. For example, you will not only map the connections between neurons of a circuit at synaptic resolution — you will also add readouts on neuron and glia cell type identity, neurotransmitters and receptors, and computational activity.

You will also build new technologies to access ever more layers of information, and to speed up data acquisition to obtain a larger number of datasets for comparative analysis. By comparing unprecedentedly detailed multidimensional brain maps of different brain conditions — from behavior, to disease and ageing — your work will help generate and test new hypotheses on biological computation.

References

A roadmap to scale connectomics to entire mammalian brains
Payne A