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Chapter 8 Reverse Engineering the 3D Structure and Sensory-Evoked Signal Flow of Rat Vibrissal Cortex Robert Egger, Vincent J. Dercksen, Christiaan P.J. de Kock, and Marcel Oberlaender Abstract Soma location, dendrite morphology, and synaptic innervation are key determinants of neuronal function. Unfortunately, conventional functional measure- ments of sensory-evoked activity in vivo yield limited structural information. In particular, when trying to infer mechanistic principles that underlie perception and behavior, interpretations from functional recordings of individual or small groups of neurons often remain ambiguous without detailed knowledge of the underlying net- work structures. Here we review a novel reverse engineering approach that allows investigating sensory-evoked signal fl ow through individual and ensembles of neu- rons within the context of their surrounding neural networks. To do so, spontaneous and sensory-evoked activity patterns are recorded from individual neurons in vivo. In addition, the complete 3D dendrite and axon projection patterns of such in vivo- characterized neurons are reconstructed and integrated into an anatomically realistic R. Egger Computational Neuroanatomy Group, Max Planck Institute for Biological Cybernetics , Spemannstraße 38-44 , Tuebingen 72076 , Germany Graduate School of Neural Information Processing , University of Tuebingen , Tuebingen , Germany V.J. Dercksen Department of Visualization and Data Analysis , Zuse Institute Berlin , Berlin , Germany C.P.J. de Kock Center for Neurogenomics and Cognitive Research , Neuroscience Campus Amsterdam, VU University Amsterdam , Amsterdam , The Netherlands M. Oberlaender (*) Computational Neuroanatomy Group, Max Planck Institute for Biological Cybernetics , Spemannstraße 38-44 , Tuebingen 72076 , Germany Bernstein Center for Computational Neuroscience , Tuebingen , Germany Digital Neuroanatomy, Max Planck Florida Institute