NEURAL CARTOGRAPHY: MAPPING THE BRAIN
WITH X-RAY AND ELECTRON MICROSCOPY

One of the grand quests in neuroscience is to build complete maps of
the brain, charting all of its cells and the connections between them.
Such wiring diagrams, called connectomes, promise to shed light on
how networks of neurons can give rise to thoughts, memories, and
actions, and to help reveal the underlying causes of neurological
diseases. Today, complete connectomes are only available for very
small organisms such as worms (104 connections) and fruit flies (107
connections). To map the immensely more complex brains of mice
(1012 connections), and ultimately humans (1014 connections), new
imaging technologies will be needed. In this talk, I will present recent innovations that are expanding the scope and detail at which we can image the brain. I will describe an automated electron microscopy system that builds 3D circuit maps from thousands of ultra-thin tissue sections, and share how we have combined this technique with in vivo experiments to investigate how neural circuits in the mouse brain implement decision-making. I will then introduce synchrotron-based X-ray nano-holography as a non-destructive, high-throughput imaging approach, and show how we used it to map large-scale circuits in the fruit fly leg and mouse cortex. In conclusion, I will argue that electron microscopy and X-ray imaging together form a synergistic, multi- scale approach that can tackle the massive scaling challenge of mapping mammalian brains.