The big and the small: challenges of imaging the brain's circuits

The relation between the structure of the nervous system and its function is more poorly understood than the relation between structure and function in any other organ system. We explore why bridging the structure-function divide is uniquely difficult in the brain. These difficulties also explain the thrust behind the enormous amount of innovation centered on microscopy in neuroscience. We highlight some recent progress and the challenges that remain. Acentral theme of biology is the relationbetween the structure and function ofthings. By structure, we mean the phys-ical form of something, a property that hu-mans can apprehend by touch (if the object is big enough) or by sight. Right now, the leading edge of this effort is the field known by the gen-eral name “structural biology ” but is focused narrowly on the shapes of molecules in order to provide insights into how proteins such as chan-nels, enzymes, and transcription factors do their jobs. The x-ray crystallography approach com