FOCUS ON MAPPING THE BRAIN REvIEw

NATURE METHOdS | VOL.10 NO.6 | JUNE 2013 | 515 Since the pioneering work of Camillo Golgi and Santiago Ramón y Cajal at the turn of the last century1,2, advances in light microscopy (LM) and neurotracing methods have been central to the progress in our understanding of anatomical organization in the mammalian brain. The Golgi silver-impregnation method allowed the visualization of neuron morphology, providing the first evidence for cell type–based and connectivity-based organization in the brain. The introduction of efficient neuroanatomical tracers in the second half of the last century greatly increased the throughput and versatility of neuronal projection mapping, which led to the identification of many anatomical pathways and circuits, and revealed the basic principles of hierarchical and laminar connectivity in sensory, motor and other brain systems3,4. The beginning of this century has seen a methodsdriven renaissance in neuroanatomy, one that is distinguished by a focus on large-scale projects that yield unprecedented amounts of anatomical data. Instead of the traditional ‘cottage-industry’ approach to studying one anatomical pathway at a time, the new projects aim to generate complete data sets—so-called projectomes and connectomes—that can be used by the scientific community as resources for answering specific experimental questions. These efforts range in scale and resolution from the macroscopic to the microscopic: from studies of the human brain by magnetic resonance imaging to reconstructions of dense neural circuits in Mapping brain circuitry with a light microscope